Datasets:

bigbio

/

bionlp_shared_task_2009

like 2

Follow

BigScience Biomedical Datasets 112

[ { "id": "8524816__text", "type": "abstract", "text": [ "Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for differential gene expression in T helper cell subsets. \nActivation of individual CD4+ T cells results in differential lymphokine expression: interleukin 2 (IL-2) is preferentially produced by T helper type 1 (TH1) cells, which are involved in cell-mediated immune responses, whereas IL-4 is synthesized by TH2 cells, which are essential for humoral immunity. The Ca(2+)-dependent factor NF-ATp plays a key role in the inducible transcription of both these lymphokine genes. However, while IL2 expression requires the contribution of Ca(2+)- and protein kinase C-dependent signals, we report that activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells. This phenomenon is due to mutually exclusive binding of NF-ATp and NF-kappa B to the P sequence, an element located 69 bp upstream of the IL4 transcription initiation site. Human IL4 promoter-mediated transcription is downregulated in Jurkat cells stimulated with the NF-kappa B-activating cytokine tumor necrosis factor alpha and suppressed in RelA-overexpressing cells. In contrast, protein kinase C stimulation or RelA overexpression does not affect the activity of a human IL4 promoter containing a mouse P sequence, which is a higher-affinity site for NF-ATp and a lower-affinity site for RelA. Thus, competition between two general transcriptional activators, RelA and NF-ATp, mediates the inhibitory effect of protein kinase C stimulation on IL4 expression and may contribute to differential gene expression in TH cells. " ], "offsets": [ [ 0, 1640 ] ] } ]

[ { "id": "8524816_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 157, 160 ] ], "normalized": [] }, { "id": "8524816_T2", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 217, 230 ] ], "normalized": [] }, { "id": "8524816_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 232, 236 ] ], "normalized": [] }, { "id": "8524816_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 359, 363 ] ], "normalized": [] }, { "id": "8524816_T5", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 463, 469 ] ], "normalized": [] }, { "id": "8524816_T6", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 565, 568 ] ], "normalized": [] }, { "id": "8524816_T7", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 692, 695 ] ], "normalized": [] }, { "id": "8524816_T8", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 868, 874 ] ], "normalized": [] }, { "id": "8524816_T9", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 950, 953 ] ], "normalized": [] }, { "id": "8524816_T10", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 991, 994 ] ], "normalized": [] }, { "id": "8524816_T11", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1111, 1138 ] ], "normalized": [] }, { "id": "8524816_T12", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1157, 1161 ] ], "normalized": [] }, { "id": "8524816_T13", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1229, 1233 ] ], "normalized": [] }, { "id": "8524816_T14", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1289, 1292 ] ], "normalized": [] }, { "id": "8524816_T15", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1369, 1375 ] ], "normalized": [] }, { "id": "8524816_T16", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1406, 1410 ] ], "normalized": [] }, { "id": "8524816_T17", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1478, 1482 ] ], "normalized": [] }, { "id": "8524816_T18", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1487, 1493 ] ], "normalized": [] }, { "id": "8524816_T19", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1561, 1564 ] ], "normalized": [] }, { "id": "8524816_T38", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1293, 1301 ] ], "normalized": [] } ]

[ { "id": "8524816_E1", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 256, 264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T3" } ] }, { "id": "8524816_E2", "type": "Gene_expression", "trigger": { "text": [ "synthesized" ], "offsets": [ [ 367, 378 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T4" } ] }, { "id": "8524816_E3", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 446, 455 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T5" } ] }, { "id": "8524816_E4", "type": "Positive_regulation", "trigger": { "text": [ "key role" ], "offsets": [ [ 478, 486 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E6" }, { "role": "Cause", "ref_id": "8524816_T5" } ] }, { "id": "8524816_E5", "type": "Positive_regulation", "trigger": { "text": [ "key role" ], "offsets": [ [ 478, 486 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E7" }, { "role": "Cause", "ref_id": "8524816_T5" } ] }, { "id": "8524816_E6", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 494, 503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E8" } ] }, { "id": "8524816_E7", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 494, 503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E9" } ] }, { "id": "8524816_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 504, 517 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T4" } ] }, { "id": "8524816_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 504, 517 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T3" } ] }, { "id": "8524816_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 569, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T6" } ] }, { "id": "8524816_E11", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 580, 588 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E10" } ] }, { "id": "8524816_E12", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 672, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E13" } ] }, { "id": "8524816_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 696, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T7" } ] }, { "id": "8524816_E14", "type": "Negative_regulation", "trigger": { "text": [ "diminished" ], "offsets": [ [ 750, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E12" } ] }, { "id": "8524816_E15", "type": "Positive_regulation", "trigger": { "text": [ "due to" ], "offsets": [ [ 831, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E14" } ] }, { "id": "8524816_E16", "type": "Positive_regulation", "trigger": { "text": [ "due to" ], "offsets": [ [ 831, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E14" }, { "role": "Cause", "ref_id": "8524816_E17" } ] }, { "id": "8524816_E17", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 857, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T8" } ] }, { "id": "8524816_E18", "type": "Gene_expression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 1162, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T12" } ] }, { "id": "8524816_E19", "type": "Positive_regulation", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 1162, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E18" } ] }, { "id": "8524816_E20", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1234, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E21" } ] }, { "id": "8524816_E21", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1234, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T13" } ] }, { "id": "8524816_E22", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1258, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T14" }, { "role": "Site", "ref_id": "8524816_T38" } ] }, { "id": "8524816_E23", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1258, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T14" }, { "role": "Cause", "ref_id": "8524816_E20" }, { "role": "Site", "ref_id": "8524816_T38" } ] }, { "id": "8524816_E24", "type": "Binding", "trigger": { "text": [ "higher-affinity site" ], "offsets": [ [ 1344, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T15" } ] }, { "id": "8524816_E25", "type": "Binding", "trigger": { "text": [ "lower-affinity site" ], "offsets": [ [ 1382, 1401 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T16" } ] }, { "id": "8524816_E26", "type": "Binding", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T18" } ] }, { "id": "8524816_E27", "type": "Negative_regulation", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E26" }, { "role": "Cause", "ref_id": "8524816_T17" } ] }, { "id": "8524816_E28", "type": "Binding", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T17" } ] }, { "id": "8524816_E29", "type": "Negative_regulation", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E28" }, { "role": "Cause", "ref_id": "8524816_T18" } ] }, { "id": "8524816_E30", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1495, 1503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E32" }, { "role": "Cause", "ref_id": "8524816_E29" } ] }, { "id": "8524816_E31", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1495, 1503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E32" }, { "role": "Cause", "ref_id": "8524816_E27" } ] }, { "id": "8524816_E32", "type": "Negative_regulation", "trigger": { "text": [ "inhibitory" ], "offsets": [ [ 1508, 1518 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_E33" } ] }, { "id": "8524816_E33", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1565, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8524816_T19" } ] } ]

[ { "id": "8524816_1", "entity_ids": [ "8524816_T2", "8524816_T3" ] } ]

[]

[ { "id": "9007200__text", "type": "abstract", "text": [ "V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T cell growth [published erratum appears in AIDS Res Hum Retroviruses 1997 May 1;13(7):633] \nWe tested the effect of three linear or two loop peptides derived from the V3 region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency virus type 1 on IL-2-driven T cell proliferation. V3-BH10, which consists of 42 amino acids and has a loop structure, suppressed IL-2-driven proliferation of all IL-2-dependent cells [Kit225, ED-40515(+), KT-3, 7-day PHA-blasts, and fresh peripheral blood mononuclear cells] tested, whereas it did not suppress the cell growth of IL-2-independent cell lines (Hut102, Molt-4, and Jurkat). This suppressive effect was also seen in IL-2-driven cell growth of CD8-positive lymphocytes purified from 7-day PHA-blasts, indicating that CD4 molecules were not required for the suppression. The treatment with anti-V3 loop monoclonal antibody (902 antibody) completely abolished the suppressive effect of V3-BH10. In addition, V3-BH10 generated the arrest of Kit225 cells and also purified CD8-positive lymphocytes in G1 phase in the presence of IL-2. Neither chromatin condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3-BH10 and IL-2. V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2 receptors nor affected tyrosyl phosphorylation of several cellular proteins (p120, p98, p96, p54, and p38), which is immediately induced by IL-2 stimulation. However, V3-BH10 enhanced IL-2-induced mRNA expression of c-fos but not c-myc or junB. Thus, the binding of V3 loop of gp120 to the cell surface molecule(s) appears to affect intracellular IL-2 signaling, which leads to the suppression of IL-2-induced T cell growth. " ], "offsets": [ [ 0, 1769 ] ] } ]

[ { "id": "9007200_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 58, 71 ] ], "normalized": [] }, { "id": "9007200_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 345, 349 ] ], "normalized": [] }, { "id": "9007200_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 458, 462 ] ], "normalized": [] }, { "id": "9007200_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 491, 495 ] ], "normalized": [] }, { "id": "9007200_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 659, 663 ] ], "normalized": [] }, { "id": "9007200_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 758, 762 ] ], "normalized": [] }, { "id": "9007200_T7", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 858, 861 ] ], "normalized": [] }, { "id": "9007200_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1166, 1170 ] ], "normalized": [] }, { "id": "9007200_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1280, 1284 ] ], "normalized": [] }, { "id": "9007200_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1323, 1327 ] ], "normalized": [] }, { "id": "9007200_T11", "type": "Protein", "text": [ "p120" ], "offsets": [ [ 1421, 1425 ] ], "normalized": [] }, { "id": "9007200_T12", "type": "Protein", "text": [ "p98" ], "offsets": [ [ 1427, 1430 ] ], "normalized": [] }, { "id": "9007200_T13", "type": "Protein", "text": [ "p96" ], "offsets": [ [ 1432, 1435 ] ], "normalized": [] }, { "id": "9007200_T14", "type": "Protein", "text": [ "p54" ], "offsets": [ [ 1437, 1440 ] ], "normalized": [] }, { "id": "9007200_T15", "type": "Protein", "text": [ "p38" ], "offsets": [ [ 1446, 1449 ] ], "normalized": [] }, { "id": "9007200_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1484, 1488 ] ], "normalized": [] }, { "id": "9007200_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1528, 1532 ] ], "normalized": [] }, { "id": "9007200_T18", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1560, 1565 ] ], "normalized": [] }, { "id": "9007200_T19", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 1574, 1579 ] ], "normalized": [] }, { "id": "9007200_T20", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 1583, 1587 ] ], "normalized": [] }, { "id": "9007200_T21", "type": "Protein", "text": [ "gp120" ], "offsets": [ [ 1621, 1626 ] ], "normalized": [] }, { "id": "9007200_T22", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1691, 1695 ] ], "normalized": [] }, { "id": "9007200_T23", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1741, 1745 ] ], "normalized": [] }, { "id": "9007200_T27", "type": "Entity", "text": [ "tyrosyl" ], "offsets": [ [ 1367, 1374 ] ], "normalized": [] }, { "id": "9007200_T34", "type": "Entity", "text": [ "V3 loop" ], "offsets": [ [ 1610, 1617 ] ], "normalized": [] } ]

[ { "id": "9007200_E1", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 1302, 1309 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E2" } ] }, { "id": "9007200_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1328, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T10" } ] }, { "id": "9007200_E3", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1358, 1366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E16" } ] }, { "id": "9007200_E4", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1358, 1366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E15" } ] }, { "id": "9007200_E5", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1358, 1366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E17" } ] }, { "id": "9007200_E6", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1358, 1366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E13" } ] }, { "id": "9007200_E7", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1358, 1366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E14" } ] }, { "id": "9007200_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T11" }, { "role": "Site", "ref_id": "9007200_T27" } ] }, { "id": "9007200_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T12" }, { "role": "Site", "ref_id": "9007200_T27" } ] }, { "id": "9007200_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T13" }, { "role": "Site", "ref_id": "9007200_T27" } ] }, { "id": "9007200_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T15" }, { "role": "Site", "ref_id": "9007200_T27" } ] }, { "id": "9007200_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T14" }, { "role": "Site", "ref_id": "9007200_T27" } ] }, { "id": "9007200_E13", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1473, 1480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E9" }, { "role": "Cause", "ref_id": "9007200_T16" } ] }, { "id": "9007200_E14", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1473, 1480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E10" }, { "role": "Cause", "ref_id": "9007200_T16" } ] }, { "id": "9007200_E15", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1473, 1480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E11" }, { "role": "Cause", "ref_id": "9007200_T16" } ] }, { "id": "9007200_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1473, 1480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E12" }, { "role": "Cause", "ref_id": "9007200_T16" } ] }, { "id": "9007200_E17", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1473, 1480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E8" }, { "role": "Cause", "ref_id": "9007200_T16" } ] }, { "id": "9007200_E18", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1519, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E23" } ] }, { "id": "9007200_E19", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1519, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E21" } ] }, { "id": "9007200_E20", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1519, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E22" } ] }, { "id": "9007200_E21", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1533, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E25" }, { "role": "Cause", "ref_id": "9007200_T17" } ] }, { "id": "9007200_E22", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1533, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E24" }, { "role": "Cause", "ref_id": "9007200_T17" } ] }, { "id": "9007200_E23", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1533, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_E26" }, { "role": "Cause", "ref_id": "9007200_T17" } ] }, { "id": "9007200_E24", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1541, 1556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T19" } ] }, { "id": "9007200_E25", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1541, 1556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T18" } ] }, { "id": "9007200_E26", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1541, 1556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T20" } ] }, { "id": "9007200_E27", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1599, 1606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9007200_T21" }, { "role": "Site", "ref_id": "9007200_T34" } ] } ]

[]

[]

[ { "id": "9277450__text", "type": "abstract", "text": [ "Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line. \nThe expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor (NF)-kappa B. Because surfactant protein (SP) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-kappa B. We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line, a human monocytic cell line. Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids. Moreover, the NF-kappa B inhibitors blocked SP-A-dependent increases in tumor necrosis factor-alpha mRNA levels. These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung. " ], "offsets": [ [ 0, 1295 ] ] } ]

[ { "id": "9277450_T1", "type": "Protein", "text": [ "Surfactant protein A" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "9277450_T2", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 1031, 1058 ] ], "normalized": [] } ]

[ { "id": "9277450_E1", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 995, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9277450_E2" } ] }, { "id": "9277450_E2", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1018, 1027 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9277450_T2" } ] } ]

[]

[]

[ { "id": "8314792__text", "type": "abstract", "text": [ "Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes. \nNuclear factor of activated T cells (NFAT) is a transcriptional activator that binds to sequences in the interleukin-2 (IL-2) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression. Electrophoretic mobility shift assays (EMSA) showed that specific NFAT binding activity could also be induced in human B cells. The B cell NFAT complex, however, was not functional, since it failed to activate transcription from an NFAT-driven chloramphenicol acetyltransferase (CAT) construct. Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells, indicating that Jun and Fos are critical for NFAT complex formation in both cell types. Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif. However, when combined with unstimulated B or T cell extracts, full-length, but not truncated, Jun/Fos heterodimers were able to form an NFAT complex, indicating the presence of a constitutively expressed nuclear factor(s) in B and T cells necessary for the formation of the NFAT complex in both cell types. An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells. We therefore propose a model whereby a core NFAT complex consisting of Jun, Fos, and a constitutive nuclear factor is formed in both T and B cells, but an additional factor and/or post-translational modification of a factor, missing in B cells, might be required for transactivation by NFAT. " ], "offsets": [ [ 0, 1744 ] ] } ]

[ { "id": "8314792_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 211, 224 ] ], "normalized": [] }, { "id": "8314792_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "8314792_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 322, 326 ] ], "normalized": [] }, { "id": "8314792_T4", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 583, 616 ] ], "normalized": [] }, { "id": "8314792_T5", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "8314792_T7", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 232, 240 ] ], "normalized": [] } ]

[ { "id": "8314792_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 185, 190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_T1" }, { "role": "Site", "ref_id": "8314792_T7" } ] }, { "id": "8314792_E2", "type": "Positive_regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 270, 281 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_E3" } ] }, { "id": "8314792_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducibility" ], "offsets": [ [ 306, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_E4" } ] }, { "id": "8314792_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 327, 337 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_T3" } ] }, { "id": "8314792_E5", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 410, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_T1" }, { "role": "Site", "ref_id": "8314792_T7" } ] }, { "id": "8314792_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 441, 448 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_E5" } ] }, { "id": "8314792_E7", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 540, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_E8" } ] }, { "id": "8314792_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 549, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8314792_T4" } ] } ]

[ { "id": "8314792_1", "entity_ids": [ "8314792_T1", "8314792_T2" ] }, { "id": "8314792_2", "entity_ids": [ "8314792_T4", "8314792_T5" ] } ]

[]

[ { "id": "8523529__text", "type": "abstract", "text": [ "Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus-infected monocytes. \nThe molecular mechanisms regulating human immunodeficiency virus (HIV) persistence in a major cell reservoir such as the macrophage remain unknown. NF-kappa B is a transcription factor involved in the regulation of the HIV long terminal repeat and is selectively activated following HIV infection of human macrophages. Although little information as to what signal transduction pathways mediate NF-kappa B activation in monocytes-macrophages is available, our previous work indicated that classical protein kinase C (PKC) isoenzymes were not involved in the HIV-mediated NF-kappa B activation. In this study, we have focused on atypical PKC isoenzymes. PKC-zeta belongs to this family and is known to be an important step in NF-kappa B activation in other cell systems. Immunoblotting experiments with U937 cells demonstrate that PKC-zeta is present in these cells, and its expression can be downmodulated by antisense oligonucleotides (AO). The HIV-mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta. In addition, cotransfection of a negative dominant molecule of PKC-zeta (PKC-zeta mut) with NF-kappa B-dependent reporter genes selectively inhibits the HIV- but not phorbol myristate acetate- or lipopolysaccharide-mediated activation of NF-kappa B. That PKC-zeta is specific in regulating NF-kappa B is concluded from the inability of PKC-zeta(mut) to interfere with the basal or phorbol myristate acetate-inducible CREB- or AP1-dependent transcriptional activity. Lastly, we demonstrate a selective inhibition of p24 production by HIV-infected human macrophages when treated with AO to PKC-zeta. Altogether, these results suggest that atypical PKC isoenzymes, including PKC-zeta, participate in the signal transduction pathways by which HIV infection results in the activation of NF-kappa B in human monocytic cells and macrophages. " ], "offsets": [ [ 0, 1964 ] ] } ]

[ { "id": "8523529_T1", "type": "Protein", "text": [ "Protein kinase C-zeta" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "8523529_T2", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 759, 767 ] ], "normalized": [] }, { "id": "8523529_T3", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 936, 944 ] ], "normalized": [] }, { "id": "8523529_T4", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 1119, 1127 ] ], "normalized": [] }, { "id": "8523529_T5", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 1192, 1200 ] ], "normalized": [] }, { "id": "8523529_T6", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 1202, 1210 ] ], "normalized": [] }, { "id": "8523529_T7", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 1384, 1392 ] ], "normalized": [] }, { "id": "8523529_T8", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 1465, 1473 ] ], "normalized": [] }, { "id": "8523529_T9", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 1546, 1550 ] ], "normalized": [] } ]

[ { "id": "8523529_E1", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 948, 955 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8523529_T3" } ] }, { "id": "8523529_E2", "type": "Negative_regulation", "trigger": { "text": [ "downmodulated" ], "offsets": [ [ 998, 1011 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8523529_E1" } ] }, { "id": "8523529_E3", "type": "Gene_expression", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1142, 1156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8523529_T5" } ] } ]

[]

[]

[ { "id": "8645254__text", "type": "abstract", "text": [ "Abundant expression of erythroid transcription factor P45 NF-E2 mRNA in human peripheral granurocytes. \nTranscription factor NF-E2 is crucial for regulation of erythroid-specific gene expression. p45 subunit of NF-E2 contains a basic-leucine zipper domain and dimerizes with the small Maf family protein to form functional NF-E2 complex. While p45 expression was shown to be restricted to erythroid cells, megakaryocytes and mast cells in hematopoietic lineage, we found in this study that p45 mRNA is abundantly transcribed in the granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in this fraction, the cells expressing p45 is most likely to be neutrophils. p45 mRNA is also expressed in HL-60 promyelocytes, albeit the expression level is much lower than that of the granulocyte fraction. HL-60 cells were found to express mafK mRNA, indicating the presence of genuine NF-E2 complex in the cells. Although p45 mRNA is transcribed from two different promoters, aNF-E2 promoter and fNF-E2 promoter, in erythroid and megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 mRNA in the neutrophils declined rapidly after transfer of the cells to in vitro culture and G-CSF could not sustain the expression from the down-regulation, suggesting the E2 may also participate in the regulation of neutrophil-specific gene expression. " ], "offsets": [ [ 0, 1644 ] ] } ]

[ { "id": "8645254_T1", "type": "Protein", "text": [ "erythroid transcription factor P45 NF-E2" ], "offsets": [ [ 23, 63 ] ], "normalized": [] }, { "id": "8645254_T2", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 196, 199 ] ], "normalized": [] }, { "id": "8645254_T3", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 344, 347 ] ], "normalized": [] }, { "id": "8645254_T4", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "8645254_T5", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 788, 791 ] ], "normalized": [] }, { "id": "8645254_T6", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 826, 829 ] ], "normalized": [] }, { "id": "8645254_T7", "type": "Protein", "text": [ "mafK" ], "offsets": [ [ 992, 996 ] ], "normalized": [] }, { "id": "8645254_T8", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1075, 1078 ] ], "normalized": [] }, { "id": "8645254_T9", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1213, 1216 ] ], "normalized": [] }, { "id": "8645254_T10", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1282, 1285 ] ], "normalized": [] }, { "id": "8645254_T11", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1316, 1319 ] ], "normalized": [] }, { "id": "8645254_T12", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1385, 1388 ] ], "normalized": [] }, { "id": "8645254_T13", "type": "Protein", "text": [ "G-CSF" ], "offsets": [ [ 1482, 1487 ] ], "normalized": [] } ]

[ { "id": "8645254_E1", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 9, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T1" } ] }, { "id": "8645254_E2", "type": "Binding", "trigger": { "text": [ "dimerizes" ], "offsets": [ [ 260, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T2" } ] }, { "id": "8645254_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T3" } ] }, { "id": "8645254_E4", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 513, 524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T4" } ] }, { "id": "8645254_E5", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 777, 787 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T5" } ] }, { "id": "8645254_E6", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 843, 852 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T6" } ] }, { "id": "8645254_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 888, 898 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T6" } ] }, { "id": "8645254_E8", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 984, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T7" } ] }, { "id": "8645254_E9", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1087, 1098 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T8" } ] }, { "id": "8645254_E10", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1099, 1103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_E9" } ] }, { "id": "8645254_E11", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1225, 1236 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T9" } ] }, { "id": "8645254_E12", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1242, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_E11" } ] }, { "id": "8645254_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1268, 1278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T10" } ] }, { "id": "8645254_E14", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1328, 1339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T11" } ] }, { "id": "8645254_E15", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1345, 1349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_E14" } ] }, { "id": "8645254_E16", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1371, 1381 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_T12" } ] }, { "id": "8645254_E17", "type": "Negative_regulation", "trigger": { "text": [ "declined" ], "offsets": [ [ 1413, 1421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_E16" } ] }, { "id": "8645254_E18", "type": "Negative_regulation", "trigger": { "text": [ "sustain" ], "offsets": [ [ 1498, 1505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8645254_E17" }, { "role": "Cause", "ref_id": "8645254_T13" } ] } ]

[]

[]

[ { "id": "7981603__text", "type": "abstract", "text": [ "Glucocorticoid-induced apoptosis of lymphoid cells. \nThe induction of cell death in lymphoid cells by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis. Although the exact mechanism by which apoptosis occurs in lymphocytes is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids. The role of chromatin degradation and endonucleases in the apoptotic process has been closely studied, as well as the involvement of several oncogenes in glucocorticoid-induced cell lysis. In addition, the clinical importance of glucocorticoid-induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention. " ], "offsets": [ [ 0, 726 ] ] } ]

[]

[]

[]

[]

[ { "id": "10331989__text", "type": "abstract", "text": [ "Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene. \nThe lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells. We have localized a 317 base pair cis-acting regulatory element, HS I, associated with a hematopoietic-specific DNase I hypersensitive site, which lies approx. 3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter. HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice. Comparative sequence analysis of HS I between human and mouse shows approx. 63% nucleotide identity with a more conserved core of 169 base pairs (86% identity). This core contains a GATA site separated by 10 base pairs from an E-box motif. The composite motif binds a multi-protein hematopoietic-specific transcription factor complex which includes GATA-1, SCL/tal-1, E2A, Lmo2 and Ldb-1. Point mutations of the GATA site abolishes HS I function, whereas mutation of the E-box motif still allows reporter gene expression in both lineages. Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor, presumably GATA-1 or GATA-2, is critical to activating or maintaining its function. Further dissection of the 317 base pair region demonstrates that, whereas all 317 base pairs are required for expression in megakaryocytes, only the 5' 62 base pairs are needed for erythroid-specific reporter expression. These findings demonstrate differential lineage requirements for expression within the HS I element. " ], "offsets": [ [ 0, 1717 ] ] } ]

[ { "id": "10331989_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 129, 135 ] ], "normalized": [] }, { "id": "10331989_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 187, 193 ] ], "normalized": [] }, { "id": "10331989_T3", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 485, 491 ] ], "normalized": [] }, { "id": "10331989_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 552, 558 ] ], "normalized": [] }, { "id": "10331989_T5", "type": "Protein", "text": [ "lacZ" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "10331989_T6", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1002, 1008 ] ], "normalized": [] }, { "id": "10331989_T7", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1010, 1013 ] ], "normalized": [] }, { "id": "10331989_T8", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 1014, 1019 ] ], "normalized": [] }, { "id": "10331989_T9", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10331989_T10", "type": "Protein", "text": [ "Lmo2" ], "offsets": [ [ 1026, 1030 ] ], "normalized": [] }, { "id": "10331989_T11", "type": "Protein", "text": [ "Ldb-1" ], "offsets": [ [ 1035, 1040 ] ], "normalized": [] }, { "id": "10331989_T12", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1322, 1328 ] ], "normalized": [] }, { "id": "10331989_T13", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 1332, 1338 ] ], "normalized": [] } ]

[ { "id": "10331989_E1", "type": "Positive_regulation", "trigger": { "text": [ "requirements" ], "offsets": [ [ 19, 31 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_E2" } ] }, { "id": "10331989_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 36, 46 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T1" } ] }, { "id": "10331989_E3", "type": "Positive_regulation", "trigger": { "text": [ "directs" ], "offsets": [ [ 510, 517 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_E4" } ] }, { "id": "10331989_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 529, 539 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T5" } ] }, { "id": "10331989_E5", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 913, 918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T6" } ] }, { "id": "10331989_E6", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 913, 918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T9" } ] }, { "id": "10331989_E7", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 913, 918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T7" } ] }, { "id": "10331989_E8", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 913, 918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T10" } ] }, { "id": "10331989_E9", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 913, 918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T11" } ] }, { "id": "10331989_E10", "type": "Binding", "trigger": { "text": [ "assembly of a protein complex" ], "offsets": [ [ 1255, 1284 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T13" } ] }, { "id": "10331989_E11", "type": "Binding", "trigger": { "text": [ "assembly of a protein complex" ], "offsets": [ [ 1255, 1284 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10331989_T12" } ] } ]

[ { "id": "10331989_1", "entity_ids": [ "10331989_T7", "10331989_T8" ] } ]

[]

[ { "id": "9195127__text", "type": "abstract", "text": [ "Biphasic control of NF-kappa B activation induced by the triggering of HLA-DR antigens expressed on B cells. \nThe regulation of NF-kappa B activation following the triggering of HLA-DR antigens by mAb L243 has been studied at various times in Raji cells. Electrophoretic mobility shift assays demonstrated a strong increase of NF-kappa B DNA binding after triggering of HLA-DR antigens. Using TNF-alpha-activity neutralizing antibodies, the authors demonstrated that the upregulation of NF-kappa B was found to depend, at later time point, on an autocrine effect of TNF-alpha secreted following triggering of HLA-DR antigens. In contrast, it was found to be TNF-alpha independent in the early time point. Moreover, the upregulation of NF-kappa B binding activity is regulated by the triggering of selected epitopes of HLA-DR antigens. In fact, mAb L243 but not the staphylococcal superantigens, staphylococcal exotoxin toxic shock syndrome toxin-I or staphylococcal enterotoxin B, regulate the NF-kappa B binding activity. " ], "offsets": [ [ 0, 1023 ] ] } ]

[ { "id": "9195127_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 393, 402 ] ], "normalized": [] }, { "id": "9195127_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 566, 575 ] ], "normalized": [] }, { "id": "9195127_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 658, 667 ] ], "normalized": [] }, { "id": "9195127_T4", "type": "Protein", "text": [ "toxic shock syndrome toxin-I" ], "offsets": [ [ 919, 947 ] ], "normalized": [] }, { "id": "9195127_T5", "type": "Protein", "text": [ "staphylococcal enterotoxin B" ], "offsets": [ [ 951, 979 ] ], "normalized": [] } ]

[ { "id": "9195127_E1", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 576, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9195127_T2" } ] }, { "id": "9195127_E2", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 585, 594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9195127_E1" } ] } ]

[]

[]

[ { "id": "9047239__text", "type": "abstract", "text": [ "A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site. \nInterleukin-3 (IL-3) is a cytokine that is expressed primarily in activated T cells. Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways. The IL-3 enhancer spanned an inducible cyclosporin A-sensitive DNase I-hypersensitive site found only in T cells. Four NFAT-like elements exist within the enhancer. The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site. One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c-binding sites, which functioned in a highly synergistic manner. We suggest that the T cell-specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins. " ], "offsets": [ [ 0, 950 ] ] } ]

[ { "id": "9047239_T1", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 34, 47 ] ], "normalized": [] }, { "id": "9047239_T2", "type": "Protein", "text": [ "Interleukin-3" ], "offsets": [ [ 145, 158 ] ], "normalized": [] }, { "id": "9047239_T3", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 160, 164 ] ], "normalized": [] }, { "id": "9047239_T4", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 309, 313 ] ], "normalized": [] }, { "id": "9047239_T5", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "9047239_T6", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 845, 849 ] ], "normalized": [] }, { "id": "9047239_T10", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 396, 404 ] ], "normalized": [] } ]

[ { "id": "9047239_E1", "type": "Positive_regulation", "trigger": { "text": [ "activated cooperatively" ], "offsets": [ [ 57, 80 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9047239_T1" } ] }, { "id": "9047239_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 188, 197 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9047239_T3" } ] }, { "id": "9047239_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 252, 261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9047239_T4" } ] }, { "id": "9047239_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 827, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9047239_T6" } ] }, { "id": "9047239_E5", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 865, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9047239_E4" } ] }, { "id": "9047239_E6", "type": "Regulation", "trigger": { "text": [ "through" ], "offsets": [ [ 876, 883 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9047239_E5" }, { "role": "Cause", "ref_id": "9047239_T5" }, { "role": "CSite", "ref_id": "9047239_T10" } ] } ]

[ { "id": "9047239_1", "entity_ids": [ "9047239_T2", "9047239_T3" ] } ]

[]

[ { "id": "7826623__text", "type": "abstract", "text": [ "T-cell functional regions of the human IL-3 proximal promoter. \nThe human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcriptional and post-transcriptional level. We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene. To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences. Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene. The promoter region between -173 and -60 contained the strongest activating elements. The transcription factor AP-1 could bind to this positive activator region of the promoter. We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA/PHA. " ], "offsets": [ [ 0, 1152 ] ] } ]

[ { "id": "7826623_T1", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "7826623_T2", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 74, 87 ] ], "normalized": [] }, { "id": "7826623_T3", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "7826623_T4", "type": "Protein", "text": [ "phytohemaglutinin" ], "offsets": [ [ 305, 322 ] ], "normalized": [] }, { "id": "7826623_T5", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 324, 327 ] ], "normalized": [] }, { "id": "7826623_T6", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 401, 405 ] ], "normalized": [] }, { "id": "7826623_T7", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 566, 570 ] ], "normalized": [] }, { "id": "7826623_T8", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 711, 715 ] ], "normalized": [] }, { "id": "7826623_T9", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 937, 941 ] ], "normalized": [] }, { "id": "7826623_T10", "type": "Protein", "text": [ "CK-1" ], "offsets": [ [ 942, 946 ] ], "normalized": [] }, { "id": "7826623_T11", "type": "Protein", "text": [ "CK-2" ], "offsets": [ [ 947, 951 ] ], "normalized": [] }, { "id": "7826623_T12", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1147, 1150 ] ], "normalized": [] } ]

[ { "id": "7826623_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 103, 112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_T3" } ] }, { "id": "7826623_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 158, 168 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_T3" } ] }, { "id": "7826623_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 172, 181 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_E2" } ] }, { "id": "7826623_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 172, 181 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_E5" } ] }, { "id": "7826623_E5", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 194, 209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_T3" } ] }, { "id": "7826623_E6", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 357, 366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_E7" } ] }, { "id": "7826623_E7", "type": "Transcription", "trigger": { "text": [ "transcription initiation" ], "offsets": [ [ 367, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_T6" } ] }, { "id": "7826623_E8", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 446, 454 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7826623_E6" }, { "role": "Cause", "ref_id": "7826623_T7" } ] } ]

[ { "id": "7826623_1", "entity_ids": [ "7826623_T2", "7826623_T3" ] }, { "id": "7826623_2", "entity_ids": [ "7826623_T4", "7826623_T5" ] } ]

[]

[ { "id": "10327050__text", "type": "abstract", "text": [ "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. \nInitiation of DNA replication requires the function of MCM gene products, which participate in ensuring that DNA replication occurs only once in the cell cycle. Expression of all mammalian genes of the MCM family is induced by growth stimulation, unlike yeast, and the mRNA levels peak at G1/S boundary. In this study, we examined the transcriptional activities of isolated human MCM gene promoters. Human MCM5 and MCM6 promoters with mutation in the E2F sites failed in promoter regulation following serum stimulation and exogenous E2F expression. In addition, we identified a novel E2F-like sequence in human MCM6 promoter which cooperates with the authentic E2F sites in E2F-dependent regulation. Forced expression of E2F1 could induce expression of all members of the endogenous MCM genes in rat embryonal fibroblast REF52 cells. Our results demonstrated that the growth-regulated expression of mammalian MCM5 and MCM6 genes, and presumably other MCM members, is primarily regulated by E2F through binding to multiple E2F sites in the promoters. " ], "offsets": [ [ 0, 1159 ] ] } ]

[ { "id": "10327050_T1", "type": "Protein", "text": [ "MCM5" ], "offsets": [ [ 46, 50 ] ], "normalized": [] }, { "id": "10327050_T2", "type": "Protein", "text": [ "MCM6" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "10327050_T3", "type": "Protein", "text": [ "MCM5" ], "offsets": [ [ 515, 519 ] ], "normalized": [] }, { "id": "10327050_T4", "type": "Protein", "text": [ "MCM6" ], "offsets": [ [ 524, 528 ] ], "normalized": [] }, { "id": "10327050_T5", "type": "Protein", "text": [ "MCM6" ], "offsets": [ [ 720, 724 ] ], "normalized": [] }, { "id": "10327050_T6", "type": "Protein", "text": [ "E2F1" ], "offsets": [ [ 830, 834 ] ], "normalized": [] }, { "id": "10327050_T7", "type": "Protein", "text": [ "MCM5" ], "offsets": [ [ 1018, 1022 ] ], "normalized": [] }, { "id": "10327050_T8", "type": "Protein", "text": [ "MCM6" ], "offsets": [ [ 1027, 1031 ] ], "normalized": [] }, { "id": "10327050_T12", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 529, 538 ] ], "normalized": [] }, { "id": "10327050_T15", "type": "Entity", "text": [ "E2F-like sequence" ], "offsets": [ [ 693, 710 ] ], "normalized": [] } ]

[ { "id": "10327050_E1", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 12, 21 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E4" } ] }, { "id": "10327050_E2", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 12, 21 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E3" } ] }, { "id": "10327050_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 22, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T1" } ] }, { "id": "10327050_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 22, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T2" } ] }, { "id": "10327050_E5", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 66, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E4" } ] }, { "id": "10327050_E6", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 66, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E3" } ] }, { "id": "10327050_E7", "type": "Negative_regulation", "trigger": { "text": [ "failed" ], "offsets": [ [ 570, 576 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E10" } ] }, { "id": "10327050_E8", "type": "Negative_regulation", "trigger": { "text": [ "failed" ], "offsets": [ [ 570, 576 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E9" } ] }, { "id": "10327050_E9", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 589, 599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T3" }, { "role": "Site", "ref_id": "10327050_T12" } ] }, { "id": "10327050_E10", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 589, 599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T4" }, { "role": "Site", "ref_id": "10327050_T12" } ] }, { "id": "10327050_E11", "type": "Regulation", "trigger": { "text": [ "cooperates" ], "offsets": [ [ 740, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E10" }, { "role": "Cause", "ref_id": "10327050_T5" }, { "role": "CSite", "ref_id": "10327050_T15" } ] }, { "id": "10327050_E12", "type": "Regulation", "trigger": { "text": [ "cooperates" ], "offsets": [ [ 740, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E9" }, { "role": "Cause", "ref_id": "10327050_T5" }, { "role": "CSite", "ref_id": "10327050_T15" } ] }, { "id": "10327050_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 816, 826 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T6" } ] }, { "id": "10327050_E14", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E17" } ] }, { "id": "10327050_E15", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E16" } ] }, { "id": "10327050_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 994, 1004 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T7" } ] }, { "id": "10327050_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 994, 1004 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T8" } ] }, { "id": "10327050_E18", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1086, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E17" }, { "role": "Cause", "ref_id": "10327050_E23" } ] }, { "id": "10327050_E19", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1086, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E16" }, { "role": "Cause", "ref_id": "10327050_E22" } ] }, { "id": "10327050_E20", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1086, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E16" }, { "role": "Cause", "ref_id": "10327050_E23" } ] }, { "id": "10327050_E21", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1086, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_E17" }, { "role": "Cause", "ref_id": "10327050_E22" } ] }, { "id": "10327050_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1111, 1118 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T8" } ] }, { "id": "10327050_E23", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1111, 1118 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10327050_T7" } ] } ]

[]

[]

[ { "id": "10200294__text", "type": "abstract", "text": [ "A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment. \nLipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. Given the deleterious effects to the host of TNF-alpha, it has been postulated that TNF-alpha gene expression must be tightly regulated. The nature of the nuclear factor(s) that control TNF-alpha gene transcription in humans remains obscure, although NF-kappaB has been suggested. Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from -550 to -487 in the human TNF-alpha promoter that contains transcriptional activity, but lacks any known NF-kappaB-binding sites. We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its amino-terminal sequence, which was used to design degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells; hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts. In addition, high level of expression of LITAF mRNA was observed predominantly in the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally, chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that LITAF plays an important role in the activation of the human TNF-alpha gene and proposes a new mechanism to control TNF-alpha gene expression. " ], "offsets": [ [ 0, 1905 ] ] } ]

[ { "id": "10200294_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 67, 94 ] ], "normalized": [] }, { "id": "10200294_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 289, 316 ] ], "normalized": [] }, { "id": "10200294_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 318, 327 ] ], "normalized": [] }, { "id": "10200294_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 408, 417 ] ], "normalized": [] }, { "id": "10200294_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 447, 456 ] ], "normalized": [] }, { "id": "10200294_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 549, 558 ] ], "normalized": [] }, { "id": "10200294_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 783, 792 ] ], "normalized": [] }, { "id": "10200294_T8", "type": "Protein", "text": [ "LPS-induced TNF-alpha factor" ], "offsets": [ [ 1300, 1328 ] ], "normalized": [] }, { "id": "10200294_T9", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1330, 1335 ] ], "normalized": [] }, { "id": "10200294_T10", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1352, 1357 ] ], "normalized": [] }, { "id": "10200294_T11", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1416, 1425 ] ], "normalized": [] }, { "id": "10200294_T12", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1480, 1485 ] ], "normalized": [] }, { "id": "10200294_T13", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1682, 1687 ] ], "normalized": [] }, { "id": "10200294_T14", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1762, 1767 ] ], "normalized": [] }, { "id": "10200294_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1823, 1832 ] ], "normalized": [] }, { "id": "10200294_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1878, 1887 ] ], "normalized": [] }, { "id": "10200294_T25", "type": "Entity", "text": [ "DNA-binding domain" ], "offsets": [ [ 725, 743 ] ], "normalized": [] } ]

[ { "id": "10200294_E1", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 56, 66 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E2" } ] }, { "id": "10200294_E2", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 95, 110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T1" } ] }, { "id": "10200294_E3", "type": "Positive_regulation", "trigger": { "text": [ "causing" ], "offsets": [ [ 268, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E4" } ] }, { "id": "10200294_E4", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 276, 285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T3" } ] }, { "id": "10200294_E5", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 457, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T5" } ] }, { "id": "10200294_E6", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 489, 498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E5" } ] }, { "id": "10200294_E7", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 541, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E8" } ] }, { "id": "10200294_E8", "type": "Transcription", "trigger": { "text": [ "gene transcription" ], "offsets": [ [ 559, 577 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T6" } ] }, { "id": "10200294_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 957, 964 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T7" }, { "role": "Site", "ref_id": "10200294_T25" } ] }, { "id": "10200294_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1226, 1235 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T9" } ] }, { "id": "10200294_E11", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1240, 1249 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E10" } ] }, { "id": "10200294_E12", "type": "Negative_regulation", "trigger": { "text": [ "Inhibition" ], "offsets": [ [ 1338, 1348 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E13" } ] }, { "id": "10200294_E13", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1363, 1373 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T10" } ] }, { "id": "10200294_E14", "type": "Negative_regulation", "trigger": { "text": [ "resulted in a reduction" ], "offsets": [ [ 1389, 1412 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E15" }, { "role": "Cause", "ref_id": "10200294_E12" } ] }, { "id": "10200294_E15", "type": "Transcription", "trigger": { "text": [ "transcripts" ], "offsets": [ [ 1426, 1437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T11" } ] }, { "id": "10200294_E16", "type": "Positive_regulation", "trigger": { "text": [ "high level" ], "offsets": [ [ 1452, 1462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E17" } ] }, { "id": "10200294_E17", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1466, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T12" } ] }, { "id": "10200294_E18", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1787, 1791 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E19" }, { "role": "Cause", "ref_id": "10200294_T14" } ] }, { "id": "10200294_E19", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1799, 1809 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T15" } ] }, { "id": "10200294_E20", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 1870, 1877 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_E21" }, { "role": "Cause", "ref_id": "10200294_T14" } ] }, { "id": "10200294_E21", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1888, 1903 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10200294_T16" } ] } ]

[ { "id": "10200294_1", "entity_ids": [ "10200294_T8", "10200294_T9" ] }, { "id": "10200294_2", "entity_ids": [ "10200294_T2", "10200294_T3" ] } ]

[]

[ { "id": "1946356__text", "type": "abstract", "text": [ "Negative regulation of human immunodeficiency virus type 1 expression in monocytes: role of the 65-kDa plus 50-kDa NF-kappa B dimer. \nAlthough monocytic cells can provide a reservoir for viral production in vivo, their regulation of human immunodeficiency virus type 1 (HIV-1) transcription can be either latent, restricted, or productive. These differences in gene expression have not been molecularly defined. In THP-1 cells with restricted HIV expression, there is an absence of DNA-protein binding complex formation with the HIV-1 promoter-enhancer associated with markedly less viral RNA production. This absence of binding was localized to the NF-kappa B region of the HIV-1 enhancer; the 65-kDa plus 50-kDa NF-kappa B heterodimer was preferentially lost. Adding purified NF-kappa B protein to nuclear extracts from cells with restricted expression overcomes this lack of binding. In addition, treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the heterodimer, suggesting the presence of an inhibitor of NF-kappa B activity. Furthermore, treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and NF-kappa B activity. Antiserum specific for NF-kappa B binding proteins, but not c-rel-specific antiserum, disrupted heterodimer complex formation. Thus, both NF-kappa B-binding complexes are needed for optimal viral transcription. Binding of the 65-kDa plus 50-kDa heterodimer to the HIV-1 enhancer can be negatively regulated in monocytes, providing one mechanism restricting HIV-1 gene expression. " ], "offsets": [ [ 0, 1620 ] ] } ]

[ { "id": "1946356_T1", "type": "Protein", "text": [ "65-kDa" ], "offsets": [ [ 96, 102 ] ], "normalized": [] }, { "id": "1946356_T2", "type": "Protein", "text": [ "50-kDa" ], "offsets": [ [ 108, 114 ] ], "normalized": [] }, { "id": "1946356_T3", "type": "Protein", "text": [ "65-kDa" ], "offsets": [ [ 695, 701 ] ], "normalized": [] }, { "id": "1946356_T4", "type": "Protein", "text": [ "50-kDa" ], "offsets": [ [ 707, 713 ] ], "normalized": [] }, { "id": "1946356_T5", "type": "Protein", "text": [ "65-kDa" ], "offsets": [ [ 1466, 1472 ] ], "normalized": [] }, { "id": "1946356_T6", "type": "Protein", "text": [ "50-kDa" ], "offsets": [ [ 1478, 1484 ] ], "normalized": [] } ]

[ { "id": "1946356_E1", "type": "Binding", "trigger": { "text": [ "heterodimer" ], "offsets": [ [ 725, 736 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_T3" }, { "role": "Theme", "ref_id": "1946356_T4" } ] }, { "id": "1946356_E2", "type": "Negative_regulation", "trigger": { "text": [ "lost" ], "offsets": [ [ 756, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_E1" } ] }, { "id": "1946356_E3", "type": "Negative_regulation", "trigger": { "text": [ "overcomes" ], "offsets": [ [ 855, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_E2" } ] }, { "id": "1946356_E4", "type": "Positive_regulation", "trigger": { "text": [ "restored" ], "offsets": [ [ 961, 969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_E1" } ] }, { "id": "1946356_E5", "type": "Negative_regulation", "trigger": { "text": [ "disrupted" ], "offsets": [ [ 1326, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_E1" } ] }, { "id": "1946356_E6", "type": "Binding", "trigger": { "text": [ "Binding" ], "offsets": [ [ 1451, 1458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_T6" } ] }, { "id": "1946356_E7", "type": "Binding", "trigger": { "text": [ "Binding" ], "offsets": [ [ 1451, 1458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_T5" } ] }, { "id": "1946356_E8", "type": "Binding", "trigger": { "text": [ "heterodimer" ], "offsets": [ [ 1485, 1496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_T5" }, { "role": "Theme", "ref_id": "1946356_T6" } ] }, { "id": "1946356_E9", "type": "Negative_regulation", "trigger": { "text": [ "negatively regulated" ], "offsets": [ [ 1526, 1546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_E6" } ] }, { "id": "1946356_E10", "type": "Negative_regulation", "trigger": { "text": [ "negatively regulated" ], "offsets": [ [ 1526, 1546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1946356_E7" } ] } ]

[]

[]

[ { "id": "9819151__text", "type": "abstract", "text": [ "Transcription factor NF-kappaB regulation of renal fibrosis during ureteral obstruction. \nIrrespective of the etiology, many kidney diseases result in inflammation and fibrosis of the tubulointerstitium, with the subsequent loss of renal function. To initiate any disease process or for any disease process to progress, there must be changes in the transcription of genes within the affected tissue. The nuclear factor-kappa B (NF-kappaB) family of transcription factors regulates genes involved in inflammation, cell proliferation, and cell differentiation. This review discusses the NF-kappaB transcription factor family in general and the association of NF-kappaB activation with cellular/molecular events of renal inflammation and fibrosis. " ], "offsets": [ [ 0, 745 ] ] } ]

[]

[]

[]

[]

[ { "id": "9219058__text", "type": "abstract", "text": [ "Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells. \nIt is known that the expression levels of intercellular adhesion molecule-1 (ICAM-1) in adult T cell leukemia(ATL) cells are high, whereas those in T-lymphoid cells are not. In order to investigate the factors that influence the induction of ICAM-1 molecules, Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 (HTLV-1) provirus were done. The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells. However, ILT-mat cells and ATL16T(-) cells, although they were ATL cells, showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression. Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells, respectively, whereas > 10 bands were detected in other ATL cells. These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell, especially the number of integration sites, is one of the factors for induction of ICAM-1 molecules. " ], "offsets": [ [ 0, 1231 ] ] } ]

[ { "id": "9219058_T1", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 34, 67 ] ], "normalized": [] }, { "id": "9219058_T2", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 197, 230 ] ], "normalized": [] }, { "id": "9219058_T3", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 232, 238 ] ], "normalized": [] }, { "id": "9219058_T4", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 397, 403 ] ], "normalized": [] }, { "id": "9219058_T5", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 473, 479 ] ], "normalized": [] }, { "id": "9219058_T6", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 626, 632 ] ], "normalized": [] }, { "id": "9219058_T7", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 816, 822 ] ], "normalized": [] }, { "id": "9219058_T8", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 838, 844 ] ], "normalized": [] }, { "id": "9219058_T9", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1213, 1219 ] ], "normalized": [] } ]

[ { "id": "9219058_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 20, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T1" } ] }, { "id": "9219058_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 176, 186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T3" } ] }, { "id": "9219058_E3", "type": "Regulation", "trigger": { "text": [ "influence" ], "offsets": [ [ 370, 379 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_E4" } ] }, { "id": "9219058_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 384, 393 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T4" } ] }, { "id": "9219058_E5", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 453, 463 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T5" } ] }, { "id": "9219058_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 638, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T6" } ] }, { "id": "9219058_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 823, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T7" } ] }, { "id": "9219058_E8", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 850, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T8" } ] }, { "id": "9219058_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1200, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9219058_T9" } ] } ]

[ { "id": "9219058_1", "entity_ids": [ "9219058_T2", "9219058_T3" ] } ]

[]

[ { "id": "9185506__text", "type": "abstract", "text": [ "Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras. \nGiant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects medium and large-sized arteries. Glucocorticoid therapy resolves clinical symptoms within hours to days, but therapy has to be continued over several years to prevent disease relapses. It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment. GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo. Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the diminished expression of inducible NO synthase. In contrast, synthesis of IFN-gamma mRNA was only slightly decreased, and expression of TGF-beta1 was unaffected. These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue. Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB-mediated cytokine production in the inflammatory lesions. Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma, whereas the activation of tissue-infiltrating macrophages was only partially affected. IL-1beta transcription was abrogated; in contrast, TGF-beta1 mRNA synthesis was steroid resistant. The persistence of TGF-beta1-transcribing macrophages, despite paralysis of T cell function, may provide an explanation for the chronicity of the disease, and may identify a novel therapeutic target in this inflammatory vasculopathy. " ], "offsets": [ [ 0, 1961 ] ] } ]

[ { "id": "9185506_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 913, 917 ] ], "normalized": [] }, { "id": "9185506_T2", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 919, 927 ] ], "normalized": [] }, { "id": "9185506_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 933, 937 ] ], "normalized": [] }, { "id": "9185506_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1029, 1038 ] ], "normalized": [] }, { "id": "9185506_T5", "type": "Protein", "text": [ "TGF-beta1" ], "offsets": [ [ 1091, 1100 ] ], "normalized": [] }, { "id": "9185506_T6", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1166, 1178 ] ], "normalized": [] }, { "id": "9185506_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1521, 1525 ] ], "normalized": [] }, { "id": "9185506_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1530, 1539 ] ], "normalized": [] }, { "id": "9185506_T9", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1628, 1636 ] ], "normalized": [] }, { "id": "9185506_T10", "type": "Protein", "text": [ "TGF-beta1" ], "offsets": [ [ 1679, 1688 ] ], "normalized": [] }, { "id": "9185506_T11", "type": "Protein", "text": [ "TGF-beta1" ], "offsets": [ [ 1746, 1755 ] ], "normalized": [] } ]

[ { "id": "9185506_E1", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T2" } ] }, { "id": "9185506_E2", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T1" } ] }, { "id": "9185506_E3", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T3" } ] }, { "id": "9185506_E4", "type": "Transcription", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 1016, 1025 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T4" } ] }, { "id": "9185506_E5", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1062, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E4" } ] }, { "id": "9185506_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1077, 1087 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T5" } ] }, { "id": "9185506_E7", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1105, 1115 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E6" } ] }, { "id": "9185506_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1148, 1158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T6" } ] }, { "id": "9185506_E9", "type": "Negative_regulation", "trigger": { "text": [ "deplete" ], "offsets": [ [ 1493, 1500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E11" } ] }, { "id": "9185506_E10", "type": "Negative_regulation", "trigger": { "text": [ "deplete" ], "offsets": [ [ 1493, 1500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E12" } ] }, { "id": "9185506_E11", "type": "Gene_expression", "trigger": { "text": [ "products" ], "offsets": [ [ 1512, 1520 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T7" } ] }, { "id": "9185506_E12", "type": "Gene_expression", "trigger": { "text": [ "products" ], "offsets": [ [ 1512, 1520 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T8" } ] }, { "id": "9185506_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1637, 1650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T9" } ] }, { "id": "9185506_E14", "type": "Negative_regulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 1655, 1664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E13" } ] }, { "id": "9185506_E15", "type": "Transcription", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 1694, 1703 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T10" } ] }, { "id": "9185506_E16", "type": "Regulation", "trigger": { "text": [ "resistant" ], "offsets": [ [ 1716, 1725 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E15" } ] }, { "id": "9185506_E17", "type": "Negative_regulation", "trigger": { "text": [ "persistence" ], "offsets": [ [ 1731, 1742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_E18" } ] }, { "id": "9185506_E18", "type": "Transcription", "trigger": { "text": [ "transcribing" ], "offsets": [ [ 1756, 1768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9185506_T11" } ] } ]

[]

[]

[ { "id": "8761381__text", "type": "abstract", "text": [ "Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. \nAlthough case-oriented evidence for an association of Epstein-Barr virus (EBV) with gastric carcinoma has been accumulating recently, the interaction(s) between EBV and gastric epithelial cells is/are largely unknown. In this study, we examined seven EBV-positive gastric carcinoma tissues for viral gene expression at the mRNA level, from which studies on the EBV oncogenicity in human epithelial cells will benefit. Reverse transcription-PCR analysis showed that all seven EBV-positive tumour tissues constitutively expressed EBV nuclear antigen (EBNA) 1 mRNA, but not EBNA2 mRNA. The EBNA transcription was initiated from one of three EBNA promoters, Qp: by contrast, both Cp and Wp were silent, thus resulting in the lack of EBNA2 mRNA. Latent membrane protein (LMP) 2A mRNA was detected in three of seven cases; however, neither LMP1 nor LMP2B mRNA was detected in any of the tumours tested. Transcripts from the BamHI-A region of the viral genome were detectable in all cases. BZLF1 mRNA and the product, an immediate-early gene for EBV replication, was not expressed in any of them, thereby suggesting that the tumour cells carried EBV genomes in a tightly latent form. These findings further extended our previous data regarding EBV latency in gastric carcinoma cells at the protein level, and have affirmed that the programme of viral gene expression in the tumour more closely resembles 'latency I' represented by Burkitt's lymphoma than 'latency II' represented by the majority of nasopharyngeal carcinomas. " ], "offsets": [ [ 0, 1660 ] ] } ]

[ { "id": "8761381_T1", "type": "Protein", "text": [ "EBV nuclear antigen (EBNA) 1" ], "offsets": [ [ 669, 697 ] ], "normalized": [] }, { "id": "8761381_T2", "type": "Protein", "text": [ "EBNA2" ], "offsets": [ [ 712, 717 ] ], "normalized": [] }, { "id": "8761381_T3", "type": "Protein", "text": [ "EBNA2" ], "offsets": [ [ 870, 875 ] ], "normalized": [] }, { "id": "8761381_T4", "type": "Protein", "text": [ "Latent membrane protein (LMP) 2A" ], "offsets": [ [ 882, 914 ] ], "normalized": [] }, { "id": "8761381_T5", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 975, 979 ] ], "normalized": [] }, { "id": "8761381_T6", "type": "Protein", "text": [ "LMP2B" ], "offsets": [ [ 984, 989 ] ], "normalized": [] }, { "id": "8761381_T7", "type": "Protein", "text": [ "BZLF1" ], "offsets": [ [ 1124, 1129 ] ], "normalized": [] } ]

[ { "id": "8761381_E1", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 659, 668 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T2" } ] }, { "id": "8761381_E2", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 659, 668 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T1" } ] }, { "id": "8761381_E3", "type": "Positive_regulation", "trigger": { "text": [ "resulting" ], "offsets": [ [ 845, 854 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_E4" } ] }, { "id": "8761381_E4", "type": "Transcription", "trigger": { "text": [ "lack" ], "offsets": [ [ 862, 866 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T3" } ] }, { "id": "8761381_E5", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 924, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T4" } ] }, { "id": "8761381_E6", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 999, 1007 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T5" } ] }, { "id": "8761381_E7", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 999, 1007 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T6" } ] }, { "id": "8761381_E8", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1205, 1214 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8761381_T7" } ] } ]

[]

[]

[ { "id": "8652841__text", "type": "abstract", "text": [ "BCL-6 expression during B-cell activation. \nTranslocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression. " ], "offsets": [ [ 0, 1606 ] ] } ]

[ { "id": "8652841_T1", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "8652841_T2", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 73, 78 ] ], "normalized": [] }, { "id": "8652841_T3", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "8652841_T4", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 322, 327 ] ], "normalized": [] }, { "id": "8652841_T5", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 448, 453 ] ], "normalized": [] }, { "id": "8652841_T6", "type": "Protein", "text": [ "CD40 ligand" ], "offsets": [ [ 603, 614 ] ], "normalized": [] }, { "id": "8652841_T7", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 657, 662 ] ], "normalized": [] }, { "id": "8652841_T8", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 702, 707 ] ], "normalized": [] }, { "id": "8652841_T9", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 782, 795 ] ], "normalized": [] }, { "id": "8652841_T10", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 862, 880 ] ], "normalized": [] }, { "id": "8652841_T11", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 882, 887 ] ], "normalized": [] }, { "id": "8652841_T12", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1053, 1058 ] ], "normalized": [] }, { "id": "8652841_T13", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1132, 1137 ] ], "normalized": [] }, { "id": "8652841_T14", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "8652841_T15", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1358, 1363 ] ], "normalized": [] }, { "id": "8652841_T16", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1588, 1593 ] ], "normalized": [] } ]

[ { "id": "8652841_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 6, 16 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T1" } ] }, { "id": "8652841_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 328, 338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T4" } ] }, { "id": "8652841_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 342, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_E2" } ] }, { "id": "8652841_E4", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 645, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T7" } ] }, { "id": "8652841_E5", "type": "Negative_regulation", "trigger": { "text": [ "downregulation" ], "offsets": [ [ 684, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T8" } ] }, { "id": "8652841_E6", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 909, 917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T11" } ] }, { "id": "8652841_E7", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1043, 1052 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_E8" } ] }, { "id": "8652841_E8", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1064, 1074 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T12" } ] }, { "id": "8652841_E9", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1122, 1131 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T13" } ] }, { "id": "8652841_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1247, 1257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T14" } ] }, { "id": "8652841_E11", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1383, 1393 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T15" } ] }, { "id": "8652841_E12", "type": "Positive_regulation", "trigger": { "text": [ "allow" ], "offsets": [ [ 1556, 1561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_E14" } ] }, { "id": "8652841_E13", "type": "Positive_regulation", "trigger": { "text": [ "allow" ], "offsets": [ [ 1556, 1561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_E15" } ] }, { "id": "8652841_E14", "type": "Positive_regulation", "trigger": { "text": [ "high-level" ], "offsets": [ [ 1577, 1587 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_E15" } ] }, { "id": "8652841_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1594, 1604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8652841_T16" } ] } ]

[]

[]

[ { "id": "9743506__text", "type": "abstract", "text": [ "Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells [see comments] \nBACKGROUND: Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed. METHODS AND RESULTS: Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) determined by electrophoretic mobility shift assay and kappaB-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription. Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05). CONCLUSIONS: The present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappaB-dependent mechanism. Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis. " ], "offsets": [ [ 0, 1743 ] ] } ]

[ { "id": "9743506_T1", "type": "Protein", "text": [ "monocyte chemotactic protein-1" ], "offsets": [ [ 27, 57 ] ], "normalized": [] }, { "id": "9743506_T2", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 94, 127 ] ], "normalized": [] }, { "id": "9743506_T3", "type": "Protein", "text": [ "monocyte chemotactic protein-1" ], "offsets": [ [ 320, 350 ] ], "normalized": [] }, { "id": "9743506_T4", "type": "Protein", "text": [ "MCP-1" ], "offsets": [ [ 352, 357 ] ], "normalized": [] }, { "id": "9743506_T5", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 395, 428 ] ], "normalized": [] }, { "id": "9743506_T6", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 430, 436 ] ], "normalized": [] }, { "id": "9743506_T7", "type": "Protein", "text": [ "MCP-1" ], "offsets": [ [ 643, 648 ] ], "normalized": [] }, { "id": "9743506_T8", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 675, 681 ] ], "normalized": [] }, { "id": "9743506_T9", "type": "Protein", "text": [ "MCP-1" ], "offsets": [ [ 790, 795 ] ], "normalized": [] }, { "id": "9743506_T10", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 810, 816 ] ], "normalized": [] }, { "id": "9743506_T11", "type": "Protein", "text": [ "MCP-1" ], "offsets": [ [ 1181, 1186 ] ], "normalized": [] }, { "id": "9743506_T12", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1191, 1197 ] ], "normalized": [] }, { "id": "9743506_T13", "type": "Protein", "text": [ "MCP-1" ], "offsets": [ [ 1356, 1361 ] ], "normalized": [] }, { "id": "9743506_T14", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1398, 1404 ] ], "normalized": [] }, { "id": "9743506_T15", "type": "Protein", "text": [ "MCP-1" ], "offsets": [ [ 1528, 1533 ] ], "normalized": [] }, { "id": "9743506_T16", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1549, 1555 ] ], "normalized": [] }, { "id": "9743506_T24", "type": "Entity", "text": [ "surface" ], "offsets": [ [ 653, 660 ] ], "normalized": [] }, { "id": "9743506_T27", "type": "Entity", "text": [ "surface" ], "offsets": [ [ 817, 824 ] ], "normalized": [] }, { "id": "9743506_T32", "type": "Entity", "text": [ "surface" ], "offsets": [ [ 1376, 1383 ] ], "normalized": [] } ]

[ { "id": "9743506_E1", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 20, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E3" } ] }, { "id": "9743506_E2", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 20, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E4" } ] }, { "id": "9743506_E3", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 58, 67 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T1" } ] }, { "id": "9743506_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 80, 90 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T2" } ] }, { "id": "9743506_E5", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 298, 302 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E7" } ] }, { "id": "9743506_E6", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 298, 302 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E8" } ] }, { "id": "9743506_E7", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 359, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T4" } ] }, { "id": "9743506_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 381, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T6" } ] }, { "id": "9743506_E9", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 630, 639 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T7" } ] }, { "id": "9743506_E10", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 661, 671 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T8" }, { "role": "AtLoc", "ref_id": "9743506_T24" } ] }, { "id": "9743506_E11", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 796, 805 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T9" } ] }, { "id": "9743506_E12", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 825, 835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T10" }, { "role": "AtLoc", "ref_id": "9743506_T27" } ] }, { "id": "9743506_E13", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 855, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E12" } ] }, { "id": "9743506_E14", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 855, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E11" } ] }, { "id": "9743506_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1346, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E18" } ] }, { "id": "9743506_E16", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1346, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E17" } ] }, { "id": "9743506_E17", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1362, 1371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T13" } ] }, { "id": "9743506_E18", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 1384, 1394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T14" }, { "role": "AtLoc", "ref_id": "9743506_T32" } ] }, { "id": "9743506_E19", "type": "Positive_regulation", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1506, 1514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T15" } ] }, { "id": "9743506_E20", "type": "Positive_regulation", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1506, 1514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_T16" } ] }, { "id": "9743506_E21", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1606, 1615 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E20" } ] }, { "id": "9743506_E22", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1606, 1615 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9743506_E19" } ] } ]

[ { "id": "9743506_1", "entity_ids": [ "9743506_T5", "9743506_T6" ] }, { "id": "9743506_2", "entity_ids": [ "9743506_T3", "9743506_T4" ] } ]

[]

[ { "id": "7998962__text", "type": "abstract", "text": [ "Constitutive nuclear NF-kappa B in cells of the monocyte lineage. \nIn monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF-kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B. (ABSTRACT TRUNCATED AT 400 WORDS) " ], "offsets": [ [ 0, 2557 ] ] } ]

[ { "id": "7998962_T1", "type": "Protein", "text": [ "p50 subunit" ], "offsets": [ [ 924, 935 ] ], "normalized": [] }, { "id": "7998962_T2", "type": "Protein", "text": [ "interleukin 6" ], "offsets": [ [ 2215, 2228 ] ], "normalized": [] }, { "id": "7998962_T3", "type": "Protein", "text": [ "interleukin 10" ], "offsets": [ [ 2230, 2244 ] ], "normalized": [] }, { "id": "7998962_T4", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 2246, 2294 ] ], "normalized": [] }, { "id": "7998962_T5", "type": "Protein", "text": [ "macrophage colony-stimulating factor" ], "offsets": [ [ 2298, 2334 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "8804437__text", "type": "abstract", "text": [ "Attenuated function of a variant form of the helix-loop-helix protein, Id-3, generated by an alternative splicing mechanism. \nThe Id family of helix-loop-helix proteins function as negative regulators of DNA binding, basic helix-loop-helix proteins in the regulation of cell growth and differentiation. We report here on the identification of a 17 kDa variant of the 14 kDa Id-3 protein termed Id-3L (long version) which possesses a unique 60 amino acid carboxy-terminus generated by read through of a 'coding intron' and alternative splicing. Northern analysis revealed expression of a minor 1.1 kb Id-3L transcript together with the predominant 0.95 kb Id-3 transcript in the majority of adult human tissues analysed. The variant Id-3L protein is functionally distinguishable from conventional Id-3 since in in vitro DNA mobility shift assays, it was greatly impaired in its ability to abrogate binding of the basic helix-loop-helix protein, E47, to an E box recognition sequence. " ], "offsets": [ [ 0, 983 ] ] } ]

[ { "id": "8804437_T1", "type": "Protein", "text": [ "Id-3" ], "offsets": [ [ 71, 75 ] ], "normalized": [] }, { "id": "8804437_T2", "type": "Protein", "text": [ "Id-3" ], "offsets": [ [ 374, 378 ] ], "normalized": [] }, { "id": "8804437_T3", "type": "Protein", "text": [ "Id-3" ], "offsets": [ [ 655, 659 ] ], "normalized": [] }, { "id": "8804437_T4", "type": "Protein", "text": [ "Id-3" ], "offsets": [ [ 796, 800 ] ], "normalized": [] }, { "id": "8804437_T5", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 944, 947 ] ], "normalized": [] } ]

[ { "id": "8804437_E1", "type": "Negative_regulation", "trigger": { "text": [ "Attenuated function" ], "offsets": [ [ 0, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8804437_T1" } ] }, { "id": "8804437_E2", "type": "Positive_regulation", "trigger": { "text": [ "generated by" ], "offsets": [ [ 77, 89 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8804437_T1" } ] }, { "id": "8804437_E3", "type": "Transcription", "trigger": { "text": [ "read through" ], "offsets": [ [ 484, 496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8804437_T2" } ] }, { "id": "8804437_E4", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 571, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8804437_T3" } ] }, { "id": "8804437_E5", "type": "Negative_regulation", "trigger": { "text": [ "abrogate" ], "offsets": [ [ 888, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8804437_E6" } ] }, { "id": "8804437_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 897, 904 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8804437_T5" } ] } ]

[]

[]

[ { "id": "10029589__text", "type": "abstract", "text": [ "The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade. \nThe alpha2beta1 integrin, a collagen receptor on platelets and megakaryocytes, is required for normal platelet function. Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92, a silencer between bp -92 and -351, and megakaryocytic enhancers in the distal 5' flank. We have now identified a 229-bp region of the distal 5' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features. Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family. The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase (MAPK) signaling pathway in regulating alpha2 integrin gene expression. Inhibition of the MAP kinase cascade with PD98059, a specific inhibitor of MAPK kinase 1, prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic. We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer. " ], "offsets": [ [ 0, 1433 ] ] } ]

[ { "id": "10029589_T1", "type": "Protein", "text": [ "alpha2 integrin" ], "offsets": [ [ 316, 331 ] ], "normalized": [] }, { "id": "10029589_T2", "type": "Protein", "text": [ "alpha2 integrin" ], "offsets": [ [ 595, 610 ] ], "normalized": [] }, { "id": "10029589_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 838, 843 ] ], "normalized": [] }, { "id": "10029589_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 844, 849 ] ], "normalized": [] }, { "id": "10029589_T5", "type": "Protein", "text": [ "alpha2 integrin" ], "offsets": [ [ 990, 1005 ] ], "normalized": [] }, { "id": "10029589_T6", "type": "Protein", "text": [ "MAPK kinase 1" ], "offsets": [ [ 1098, 1111 ] ], "normalized": [] }, { "id": "10029589_T7", "type": "Protein", "text": [ "alpha2 integrin" ], "offsets": [ [ 1145, 1160 ] ], "normalized": [] }, { "id": "10029589_T8", "type": "Protein", "text": [ "alpha2 integrin" ], "offsets": [ [ 1292, 1307 ] ], "normalized": [] }, { "id": "10029589_T9", "type": "Protein", "text": [ "alpha2 integrin" ], "offsets": [ [ 1407, 1422 ] ], "normalized": [] } ]

[ { "id": "10029589_E1", "type": "Regulation", "trigger": { "text": [ "Transcriptional regulation" ], "offsets": [ [ 282, 308 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T1" } ] }, { "id": "10029589_E2", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 388, 396 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E1" } ] }, { "id": "10029589_E3", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 749, 757 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E6" } ] }, { "id": "10029589_E4", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 749, 757 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E5" } ] }, { "id": "10029589_E5", "type": "Binding", "trigger": { "text": [ "complex formation" ], "offsets": [ [ 800, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T3" } ] }, { "id": "10029589_E6", "type": "Binding", "trigger": { "text": [ "complex formation" ], "offsets": [ [ 800, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T4" } ] }, { "id": "10029589_E7", "type": "Positive_regulation", "trigger": { "text": [ "requirement" ], "offsets": [ [ 862, 873 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E9" } ] }, { "id": "10029589_E8", "type": "Positive_regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 905, 909 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E9" } ] }, { "id": "10029589_E9", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 979, 989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E10" } ] }, { "id": "10029589_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1011, 1021 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T5" } ] }, { "id": "10029589_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 1085, 1094 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T6" } ] }, { "id": "10029589_E12", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1113, 1122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E13" } ] }, { "id": "10029589_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1127, 1137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T7" } ] }, { "id": "10029589_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1274, 1284 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_T8" } ] }, { "id": "10029589_E15", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 1313, 1321 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10029589_E14" } ] } ]

[]

[]

[ { "id": "7935451__text", "type": "abstract", "text": [ "Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA (p65)-mediated induction of the c-rel gene. \nThe tax gene product of human T-cell leukemia virus type I (HTLV-I) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth. Tax acts indirectly by inducing or modifying the action of various host transcription factors, including members of the NF-kappa B/Rel family of enhancer-binding proteins. In resting T cells, many of these NF-kappa B/Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins, including I kappa B alpha. HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes; however, the biochemical mechanism(s) underlying this response remains poorly understood. In this study, we demonstrate that Tax-stimulated nuclear expression of NF-kappa B in both HTLV-I-infected and Tax-transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha. In contrast to prior in vitro studies, at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation, thereby promoting the nuclear translocation of the active NF-kappa B complex. We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA (p65) subunit of NF-kappa B, which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element. In normal cells, the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production, indicating the presence of an autoregulatory loop. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1877 ] ] } ]

[ { "id": "7935451_T1", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "7935451_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 112, 127 ] ], "normalized": [] }, { "id": "7935451_T3", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 132, 136 ] ], "normalized": [] }, { "id": "7935451_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "7935451_T5", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 186, 189 ] ], "normalized": [] }, { "id": "7935451_T6", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 399, 402 ] ], "normalized": [] }, { "id": "7935451_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 716, 731 ] ], "normalized": [] }, { "id": "7935451_T8", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 740, 743 ] ], "normalized": [] }, { "id": "7935451_T9", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 838, 843 ] ], "normalized": [] }, { "id": "7935451_T10", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 980, 983 ] ], "normalized": [] }, { "id": "7935451_T11", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1056, 1059 ] ], "normalized": [] }, { "id": "7935451_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1162, 1177 ] ], "normalized": [] }, { "id": "7935451_T13", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1268, 1283 ] ], "normalized": [] }, { "id": "7935451_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1493, 1496 ] ], "normalized": [] }, { "id": "7935451_T15", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1518, 1523 ] ], "normalized": [] }, { "id": "7935451_T16", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1555, 1559 ] ], "normalized": [] }, { "id": "7935451_T17", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1561, 1564 ] ], "normalized": [] }, { "id": "7935451_T18", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1626, 1631 ] ], "normalized": [] }, { "id": "7935451_T19", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1740, 1745 ] ], "normalized": [] } ]

[ { "id": "7935451_E1", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 77, 92 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T2" } ] }, { "id": "7935451_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 97, 108 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T2" } ] }, { "id": "7935451_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 744, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T8" } ] }, { "id": "7935451_E4", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 755, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_E5" }, { "role": "Cause", "ref_id": "7935451_E3" } ] }, { "id": "7935451_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 789, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T9" } ] }, { "id": "7935451_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1109, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T12" } ] }, { "id": "7935451_E7", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1147, 1158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T12" } ] }, { "id": "7935451_E8", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 1303, 1313 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T13" } ] }, { "id": "7935451_E9", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1374, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T13" } ] }, { "id": "7935451_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1497, 1506 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_E11" }, { "role": "Cause", "ref_id": "7935451_T14" } ] }, { "id": "7935451_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1524, 1534 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T15" } ] }, { "id": "7935451_E12", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1538, 1547 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_E10" }, { "role": "Cause", "ref_id": "7935451_T17" } ] }, { "id": "7935451_E13", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 1595, 1604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_E14" }, { "role": "Cause", "ref_id": "7935451_T18" } ] }, { "id": "7935451_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1605, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T18" } ] }, { "id": "7935451_E15", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1716, 1728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T19" } ] }, { "id": "7935451_E16", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1754, 1761 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_E17" }, { "role": "Cause", "ref_id": "7935451_E15" } ] }, { "id": "7935451_E17", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1780, 1790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7935451_T19" } ] } ]

[ { "id": "7935451_1", "entity_ids": [ "7935451_T3", "7935451_T4" ] }, { "id": "7935451_2", "entity_ids": [ "7935451_T16", "7935451_T17" ] } ]

[]

[ { "id": "9053449__text", "type": "abstract", "text": [ "Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription. \nNF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha, despite the fact that both stimuli activate NF-kappa B. Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-kappa B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression. " ], "offsets": [ [ 0, 1489 ] ] } ]

[ { "id": "9053449_T1", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 15, 20 ] ], "normalized": [] }, { "id": "9053449_T2", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 21, 25 ] ], "normalized": [] }, { "id": "9053449_T3", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 75, 102 ] ], "normalized": [] }, { "id": "9053449_T4", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 111, 122 ] ], "normalized": [] }, { "id": "9053449_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 331, 334 ] ], "normalized": [] }, { "id": "9053449_T6", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 434, 445 ] ], "normalized": [] }, { "id": "9053449_T7", "type": "Protein", "text": [ "phytohemagglutin" ], "offsets": [ [ 597, 613 ] ], "normalized": [] }, { "id": "9053449_T8", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 615, 618 ] ], "normalized": [] }, { "id": "9053449_T9", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 659, 670 ] ], "normalized": [] }, { "id": "9053449_T10", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 719, 746 ] ], "normalized": [] }, { "id": "9053449_T11", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 828, 839 ] ], "normalized": [] }, { "id": "9053449_T12", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 863, 868 ] ], "normalized": [] }, { "id": "9053449_T13", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 923, 926 ] ], "normalized": [] }, { "id": "9053449_T14", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "9053449_T15", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1052, 1057 ] ], "normalized": [] }, { "id": "9053449_T16", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1072, 1077 ] ], "normalized": [] }, { "id": "9053449_T17", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 1116, 1127 ] ], "normalized": [] }, { "id": "9053449_T18", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1155, 1158 ] ], "normalized": [] }, { "id": "9053449_T19", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1204, 1209 ] ], "normalized": [] }, { "id": "9053449_T20", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 1260, 1271 ] ], "normalized": [] }, { "id": "9053449_T21", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1368, 1373 ] ], "normalized": [] }, { "id": "9053449_T22", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 1460, 1471 ] ], "normalized": [] }, { "id": "9053449_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 840, 848 ] ], "normalized": [] } ]

[ { "id": "9053449_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 103, 110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E2" }, { "role": "Cause", "ref_id": "9053449_T3" } ] }, { "id": "9053449_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 123, 136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T4" } ] }, { "id": "9053449_E3", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 420, 429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T6" } ] }, { "id": "9053449_E4", "type": "Positive_regulation", "trigger": { "text": [ "higher levels" ], "offsets": [ [ 642, 655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T9" } ] }, { "id": "9053449_E5", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 896, 905 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E9" }, { "role": "Cause", "ref_id": "9053449_T12" } ] }, { "id": "9053449_E6", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 896, 905 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E8" }, { "role": "Cause", "ref_id": "9053449_T12" } ] }, { "id": "9053449_E7", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 896, 905 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E10" }, { "role": "Cause", "ref_id": "9053449_T12" } ] }, { "id": "9053449_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 936, 945 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T11" }, { "role": "Cause", "ref_id": "9053449_T13" }, { "role": "Site", "ref_id": "9053449_T27" } ] }, { "id": "9053449_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 936, 945 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T11" }, { "role": "Site", "ref_id": "9053449_T27" } ] }, { "id": "9053449_E10", "type": "Positive_regulation", "trigger": { "text": [ "synergistic activation" ], "offsets": [ [ 961, 983 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T14" } ] }, { "id": "9053449_E11", "type": "Positive_regulation", "trigger": { "text": [ "synergistic activation" ], "offsets": [ [ 961, 983 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T15" } ] }, { "id": "9053449_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1003, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T15" } ] }, { "id": "9053449_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1003, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T14" } ] }, { "id": "9053449_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1078, 1087 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T16" } ] }, { "id": "9053449_E15", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1092, 1100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E16" }, { "role": "Cause", "ref_id": "9053449_E14" } ] }, { "id": "9053449_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1133, 1143 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T17" } ] }, { "id": "9053449_E17", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1219, 1228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E19" } ] }, { "id": "9053449_E18", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1219, 1228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E20" } ] }, { "id": "9053449_E19", "type": "Positive_regulation", "trigger": { "text": [ "upregulate" ], "offsets": [ [ 1249, 1259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E21" } ] }, { "id": "9053449_E20", "type": "Positive_regulation", "trigger": { "text": [ "upregulate" ], "offsets": [ [ 1249, 1259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E21" }, { "role": "Cause", "ref_id": "9053449_T18" } ] }, { "id": "9053449_E21", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1272, 1285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T20" } ] }, { "id": "9053449_E22", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1349, 1359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T21" } ] }, { "id": "9053449_E23", "type": "Positive_regulation", "trigger": { "text": [ "upregulating" ], "offsets": [ [ 1447, 1459 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_E24" } ] }, { "id": "9053449_E24", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1477, 1487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9053449_T22" } ] } ]

[ { "id": "9053449_1", "entity_ids": [ "9053449_T7", "9053449_T8" ] } ]

[]

[ { "id": "2122173__text", "type": "abstract", "text": [ "Interferon-gamma and the sexual dimorphism of autoimmunity. \nThe sexual difference in the incidence of autoimmune diseases has remained an enigma for many years. In the examination of the induction of autoimmunity in transgenic mice, evidence has been obtained further implicating the lymphokine interferon-gamma in the etiology of autoimmunity. Sex steroid regulation of the production of this molecule, as well as other cytokines, may help explain the gender-specific differences in the immune system, including autoimmunity. " ], "offsets": [ [ 0, 528 ] ] } ]

[ { "id": "2122173_T1", "type": "Protein", "text": [ "Interferon-gamma" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "2122173_T2", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 296, 312 ] ], "normalized": [] } ]

[ { "id": "2122173_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 358, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2122173_E2" } ] }, { "id": "2122173_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 376, 386 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2122173_T2" } ] } ]

[]

[]

[ { "id": "9261367__text", "type": "abstract", "text": [ "Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists. \nHuman immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation response element (TAR) and, along with other cellular factors, increases viral transcription initiation and elongation. Tat also superactivates the HIV-1 promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated LTR superactivation. In this study, a combined pharmacologic and genetic strategy using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Go-6976, and a stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. In addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days. The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti-Tat sFv intrabodies alone. Together, these results suggest that in future clinical gene therapy trials, a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit. " ], "offsets": [ [ 0, 1818 ] ] } ]

[ { "id": "9261367_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 102, 105 ] ], "normalized": [] }, { "id": "9261367_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 204, 207 ] ], "normalized": [] }, { "id": "9261367_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 508, 511 ] ], "normalized": [] }, { "id": "9261367_T4", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 598, 625 ] ], "normalized": [] }, { "id": "9261367_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "9261367_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 767, 770 ] ], "normalized": [] }, { "id": "9261367_T7", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 963, 966 ] ], "normalized": [] }, { "id": "9261367_T8", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1306, 1309 ] ], "normalized": [] }, { "id": "9261367_T9", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1566, 1569 ] ], "normalized": [] } ]

[ { "id": "9261367_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 357, 364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9261367_T2" } ] } ]

[]

[]

[ { "id": "9209284__text", "type": "abstract", "text": [ "AP-1 derived from mature monocytes and astrocytes preferentially interacts with the HTLV-I promoter central 21 bp repeat. \nCharacterization of the cellular transcription factors interacting with the human T cell lymphotropic virus type I (HTLV-I) long terminal repeat (LTR) is essential to dissecting the mechanisms involved in viral transcription that may be pertinent to the oncogenic and neuropathogenic processes associated with HTLV-I infection in both the immune and nervous systems. Electrophoretic mobility shift (EMS) analyses utilizing oligonucleotides homologous to each of the 21 bp repeat elements reacted with nuclear extracts derived from cell lines of lymphocytic, monocytic, neuronal, and glial cell origin have demonstrated differential binding of cellular factors to the three 21 bp repeats (1-4). ATF/CREB and Sp family members interacted with the 21 bp repeats to form DNA-protein complexes common to all cell types examined. However, a unique DNA-protein complex was detected when the promoter central 21 bp repeat was reacted with nuclear extracts derived from either the U-373 MG glioblastoma cell line or the THP-1 mature monocytic cell line. Based on nucleotide sequence requirements and immunoreactivity, we demonstrate that this DNA-protein complex is comprised of the AP-1 components, Fos and Jun. " ], "offsets": [ [ 0, 1327 ] ] } ]

[]

[]

[]

[]

[ { "id": "1313226__text", "type": "abstract", "text": [ "Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes. \nWe have examined the effect of leukotriene B4 (LTB4), a potent lipid proinflammatory mediator, on the expression of the proto-oncogenes c-jun and c-fos. In addition, we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation. LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner. The c-jun mRNA, which is constitutively expressed in human peripheral-blood monocytes at relatively high levels, was also slightly augmented by LTB4, although to a much lower extent than c-fos. The kinetics of expression of the two genes were also slightly different, with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min. Both messages rapidly declined thereafter. Stability of the c-fos and c-jun mRNA was not affected by LTB4, as assessed after actinomycin D treatment. Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold. Resting monocytes contained nuclear factors binding to the AP-1 element, but stimulation of monocytes with LTB4 induced greater AP-1-binding activity of nuclear proteins. These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1-binding proto-oncogene products. " ], "offsets": [ [ 0, 1488 ] ] } ]

[ { "id": "1313226_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 26, 31 ] ], "normalized": [] }, { "id": "1313226_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 36, 41 ] ], "normalized": [] }, { "id": "1313226_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "1313226_T4", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 254, 259 ] ], "normalized": [] }, { "id": "1313226_T5", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 423, 428 ] ], "normalized": [] }, { "id": "1313226_T6", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 485, 490 ] ], "normalized": [] }, { "id": "1313226_T7", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 668, 673 ] ], "normalized": [] }, { "id": "1313226_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 754, 759 ] ], "normalized": [] }, { "id": "1313226_T9", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 813, 818 ] ], "normalized": [] }, { "id": "1313226_T10", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 890, 895 ] ], "normalized": [] }, { "id": "1313226_T11", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 900, 905 ] ], "normalized": [] }, { "id": "1313226_T12", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1071, 1076 ] ], "normalized": [] }, { "id": "1313226_T13", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] } ]

[ { "id": "1313226_E1", "type": "Positive_regulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 15, 25 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E4" } ] }, { "id": "1313226_E2", "type": "Positive_regulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 15, 25 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E3" } ] }, { "id": "1313226_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 47, 60 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T1" } ] }, { "id": "1313226_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 47, 60 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T2" } ] }, { "id": "1313226_E5", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 129, 135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E8" } ] }, { "id": "1313226_E6", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 129, 135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E7" } ] }, { "id": "1313226_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 210, 220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T3" } ] }, { "id": "1313226_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 210, 220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T4" } ] }, { "id": "1313226_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 391, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E10" } ] }, { "id": "1313226_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 405, 415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T5" } ] }, { "id": "1313226_E11", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 521, 530 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T6" } ] }, { "id": "1313226_E12", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 581, 592 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E11" } ] }, { "id": "1313226_E13", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 612, 621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E11" } ] }, { "id": "1313226_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 691, 701 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T9" } ] }, { "id": "1313226_E15", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 691, 701 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T8" } ] }, { "id": "1313226_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 691, 701 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T8" } ] }, { "id": "1313226_E17", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 691, 701 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T9" } ] }, { "id": "1313226_E18", "type": "Positive_regulation", "trigger": { "text": [ "reaching a peak" ], "offsets": [ [ 765, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E17" } ] }, { "id": "1313226_E19", "type": "Positive_regulation", "trigger": { "text": [ "reaching a peak" ], "offsets": [ [ 765, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E15" } ] }, { "id": "1313226_E20", "type": "Negative_regulation", "trigger": { "text": [ "declined" ], "offsets": [ [ 852, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T8" } ] }, { "id": "1313226_E21", "type": "Negative_regulation", "trigger": { "text": [ "declined" ], "offsets": [ [ 852, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T9" } ] }, { "id": "1313226_E22", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 919, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T11" } ] }, { "id": "1313226_E23", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 919, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T10" } ] }, { "id": "1313226_E24", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1036, 1045 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E27" } ] }, { "id": "1313226_E25", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1036, 1045 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_E26" } ] }, { "id": "1313226_E26", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1050, 1063 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T13" } ] }, { "id": "1313226_E27", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1050, 1063 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1313226_T12" } ] } ]

[]

[]

[ { "id": "2407588__text", "type": "abstract", "text": [ "Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression. \nAntibodies are produced exclusively in B lymphocytes. The expression of the antibody-encoding genes, the immunoglobulin (Ig) genes, is also restricted to B cells. The octamer sequence ATGCAAAT is present in the promoter and the enhancer of Ig genes, and plays an important role in its tissue-specific expression. This sequence motif is a binding site for nuclear proteins, the so-called octamer transcription factors (Oct or OTF factors). The Oct-1 protein is present in all cell types analyzed so far, whereas Oct-2A and Oct-2B are found mainly in B lymphocytes. All three proteins show the same sequence specificity and binding affinity. It appears that the B cell-specific expression of Ig genes is mediated at least in part by cell type-specific Oct factors, and that there are both quantitative and qualitative differences between Oct-1 and Oct-2 factors. Recently, a number of other octamer factor variants were identified. Many of these may be created by alternative splicing of a primary transcript of one Oct factor gene and may serve a specific function in the fine tuning of gene expression. " ], "offsets": [ [ 0, 1199 ] ] } ]

[ { "id": "2407588_T1", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 539, 544 ] ], "normalized": [] }, { "id": "2407588_T2", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "2407588_T3", "type": "Protein", "text": [ "Oct-2B" ], "offsets": [ [ 618, 624 ] ], "normalized": [] }, { "id": "2407588_T4", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 932, 937 ] ], "normalized": [] }, { "id": "2407588_T5", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 942, 947 ] ], "normalized": [] } ]

[ { "id": "2407588_E1", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 556, 563 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2407588_T1" } ] }, { "id": "2407588_E2", "type": "Gene_expression", "trigger": { "text": [ "found" ], "offsets": [ [ 629, 634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2407588_T3" } ] }, { "id": "2407588_E3", "type": "Gene_expression", "trigger": { "text": [ "found" ], "offsets": [ [ 629, 634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2407588_T2" } ] } ]

[]

[]

[ { "id": "8605348__text", "type": "abstract", "text": [ "Coexpression of the interleukin-13 and interleukin-4 genes correlates with their physical linkage in the cytokine gene cluster on human chromosome 5q23-31. \nInterleukin-13 (IL-13) and IL-4 are cytokines produced by T cells that are encoded by the q23-31 region of human chromosome 5. To investigate the regulation of IL-13 gene expression by T cells, we isolated and sequenced the human IL-13 gene, analyzed its 5'-flanking region for potential transcriptional activation elements, and examined its expression in nontransformed T-lineage cell populations. The human IL-13 gene was located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG island. The IL-13 gene 5' flank region included a segment with sequence homology to P elements of the IL-4 promoter involved in transcriptional activation in T cells. Mutation of the IL-13 P element site significantly reduced IL-13 promoter activity in response to T-cell activation. Oligonucleotides containing the IL-13 or IL-4 P element sites specifically bound the transcriptional activator protein, nuclear factor-activated T cells, preformed (NF-ATp), when incubated with nuclear protein extracts from activated T cells. Similar to IL-4, IL-13 mRNA expression was highest in T-cell populations enriched for cells that had previously been primed in vivo or in vitro, indicating that priming increases the expression of the IL-13 and IL-4 genes in a coordinate manner. Because the primed T cells contain higher levels of nuclear NF-ATp, capable of binding to P elements of the IL-4 and IL-13 promoters, than do freshly-isolated T cells, the NF-AT-binding P elements are attractive candidates to mediate the coordinate expression of these two cytokine genes. " ], "offsets": [ [ 0, 1714 ] ] } ]

[ { "id": "8605348_T1", "type": "Protein", "text": [ "interleukin-13" ], "offsets": [ [ 20, 34 ] ], "normalized": [] }, { "id": "8605348_T2", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 39, 52 ] ], "normalized": [] }, { "id": "8605348_T3", "type": "Protein", "text": [ "Interleukin-13" ], "offsets": [ [ 157, 171 ] ], "normalized": [] }, { "id": "8605348_T4", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 173, 178 ] ], "normalized": [] }, { "id": "8605348_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 184, 188 ] ], "normalized": [] }, { "id": "8605348_T6", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 317, 322 ] ], "normalized": [] }, { "id": "8605348_T7", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 387, 392 ] ], "normalized": [] }, { "id": "8605348_T8", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "8605348_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 613, 617 ] ], "normalized": [] }, { "id": "8605348_T10", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 664, 669 ] ], "normalized": [] }, { "id": "8605348_T11", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 754, 758 ] ], "normalized": [] }, { "id": "8605348_T12", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "8605348_T13", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 878, 883 ] ], "normalized": [] }, { "id": "8605348_T14", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "8605348_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "8605348_T16", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1101, 1107 ] ], "normalized": [] }, { "id": "8605348_T17", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1190, 1194 ] ], "normalized": [] }, { "id": "8605348_T18", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1196, 1201 ] ], "normalized": [] }, { "id": "8605348_T19", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1380, 1385 ] ], "normalized": [] }, { "id": "8605348_T20", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "8605348_T21", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1485, 1491 ] ], "normalized": [] }, { "id": "8605348_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1533, 1537 ] ], "normalized": [] }, { "id": "8605348_T23", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1542, 1547 ] ], "normalized": [] }, { "id": "8605348_T30", "type": "Entity", "text": [ "P elements" ], "offsets": [ [ 736, 746 ] ], "normalized": [] }, { "id": "8605348_T34", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 884, 892 ] ], "normalized": [] }, { "id": "8605348_T36", "type": "Entity", "text": [ "P element sites" ], "offsets": [ [ 982, 997 ] ], "normalized": [] }, { "id": "8605348_T43", "type": "Entity", "text": [ "P elements" ], "offsets": [ [ 1515, 1525 ] ], "normalized": [] } ]

[ { "id": "8605348_E1", "type": "Gene_expression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 0, 12 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T2" } ] }, { "id": "8605348_E2", "type": "Gene_expression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 0, 12 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T1" } ] }, { "id": "8605348_E3", "type": "Binding", "trigger": { "text": [ "linkage" ], "offsets": [ [ 90, 97 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T1" }, { "role": "Theme", "ref_id": "8605348_T2" } ] }, { "id": "8605348_E4", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 203, 211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T5" } ] }, { "id": "8605348_E5", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 203, 211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T4" } ] }, { "id": "8605348_E6", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 303, 313 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E7" } ] }, { "id": "8605348_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 328, 338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T6" } ] }, { "id": "8605348_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 499, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T7" } ] }, { "id": "8605348_E9", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 768, 776 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E10" }, { "role": "Cause", "ref_id": "8605348_T11" }, { "role": "CSite", "ref_id": "8605348_T30" } ] }, { "id": "8605348_E10", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 780, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T11" } ] }, { "id": "8605348_E11", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 870, 877 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E12" } ] }, { "id": "8605348_E12", "type": "Regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 902, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T13" }, { "role": "Site", "ref_id": "8605348_T34" } ] }, { "id": "8605348_E13", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1011, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T14" }, { "role": "Theme", "ref_id": "8605348_T16" }, { "role": "Site", "ref_id": "8605348_T36" } ] }, { "id": "8605348_E14", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1011, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T15" }, { "role": "Theme", "ref_id": "8605348_T16" }, { "role": "Site", "ref_id": "8605348_T36" } ] }, { "id": "8605348_E15", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1207, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T17" } ] }, { "id": "8605348_E16", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1207, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T18" } ] }, { "id": "8605348_E17", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1348, 1357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E19" } ] }, { "id": "8605348_E18", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1348, 1357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E20" } ] }, { "id": "8605348_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1362, 1372 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T19" } ] }, { "id": "8605348_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1362, 1372 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T20" } ] }, { "id": "8605348_E21", "type": "Positive_regulation", "trigger": { "text": [ "higher levels" ], "offsets": [ [ 1460, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T21" } ] }, { "id": "8605348_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1504, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T21" }, { "role": "Theme", "ref_id": "8605348_T22" }, { "role": "Site", "ref_id": "8605348_T43" } ] }, { "id": "8605348_E23", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1504, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T21" }, { "role": "Theme", "ref_id": "8605348_T23" }, { "role": "Site", "ref_id": "8605348_T43" } ] }, { "id": "8605348_E24", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1651, 1658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E26" } ] }, { "id": "8605348_E25", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1651, 1658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_E27" } ] }, { "id": "8605348_E26", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1674, 1684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T23" } ] }, { "id": "8605348_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1674, 1684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8605348_T22" } ] } ]

[ { "id": "8605348_1", "entity_ids": [ "8605348_T3", "8605348_T4" ] } ]

[]

[ { "id": "8668213__text", "type": "abstract", "text": [ "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes. \nTranscription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response. We have identified two new isoforms of the transcription factor NFAT1 (previously termed NFATp) that are the predominant isoforms expressed in murine and human T cells. When expressed in Jurkat T cells, recombinant NFAT1 is regulated, as expected, by the calmodulin-dependent phosphatase calcineurin, and its function is inhibited by the immunosuppressive agent cyclosporin A (CsA). Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA. Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA-sensitive manner following ionomycin stimulation. When expressed in COS cells, however, NFAT1 is capable of transactivation, but it is not regulated correctly: its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate. Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response. " ], "offsets": [ [ 0, 1665 ] ] } ]

[ { "id": "8668213_T1", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 12, 17 ] ], "normalized": [] }, { "id": "8668213_T2", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 19, 24 ] ], "normalized": [] }, { "id": "8668213_T3", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 324, 329 ] ], "normalized": [] }, { "id": "8668213_T4", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 349, 354 ] ], "normalized": [] }, { "id": "8668213_T5", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 475, 480 ] ], "normalized": [] }, { "id": "8668213_T6", "type": "Protein", "text": [ "calmodulin" ], "offsets": [ [ 515, 525 ] ], "normalized": [] }, { "id": "8668213_T7", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 674, 679 ] ], "normalized": [] }, { "id": "8668213_T8", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 938, 943 ] ], "normalized": [] }, { "id": "8668213_T9", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1137, 1142 ] ], "normalized": [] }, { "id": "8668213_T10", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1380, 1385 ] ], "normalized": [] }, { "id": "8668213_T11", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1419, 1432 ] ], "normalized": [] }, { "id": "8668213_T12", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 1434, 1447 ] ], "normalized": [] }, { "id": "8668213_T13", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1449, 1476 ] ], "normalized": [] }, { "id": "8668213_T14", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 1482, 1530 ] ], "normalized": [] }, { "id": "8668213_T15", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1569, 1574 ] ], "normalized": [] } ]

[ { "id": "8668213_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1104, 1113 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T9" } ] }, { "id": "8668213_E2", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1390, 1397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E8" } ] }, { "id": "8668213_E3", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1390, 1397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E7" } ] }, { "id": "8668213_E4", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1390, 1397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E9" } ] }, { "id": "8668213_E5", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1390, 1397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E6" } ] }, { "id": "8668213_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1398, 1411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T14" } ] }, { "id": "8668213_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1398, 1411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T12" } ] }, { "id": "8668213_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1398, 1411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T13" } ] }, { "id": "8668213_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1398, 1411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T11" } ] }, { "id": "8668213_E10", "type": "Positive_regulation", "trigger": { "text": [ "contributes" ], "offsets": [ [ 1575, 1586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E17" }, { "role": "Cause", "ref_id": "8668213_T15" } ] }, { "id": "8668213_E11", "type": "Positive_regulation", "trigger": { "text": [ "contributes" ], "offsets": [ [ 1575, 1586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E15" }, { "role": "Cause", "ref_id": "8668213_T15" } ] }, { "id": "8668213_E12", "type": "Positive_regulation", "trigger": { "text": [ "contributes" ], "offsets": [ [ 1575, 1586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E16" }, { "role": "Cause", "ref_id": "8668213_T15" } ] }, { "id": "8668213_E13", "type": "Positive_regulation", "trigger": { "text": [ "contributes" ], "offsets": [ [ 1575, 1586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_E14" }, { "role": "Cause", "ref_id": "8668213_T15" } ] }, { "id": "8668213_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1608, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T14" } ] }, { "id": "8668213_E15", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1608, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T12" } ] }, { "id": "8668213_E16", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1608, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T13" } ] }, { "id": "8668213_E17", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1608, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8668213_T11" } ] } ]

[ { "id": "8668213_1", "entity_ids": [ "8668213_T1", "8668213_T2" ] } ]

[]

[ { "id": "9817603__text", "type": "abstract", "text": [ "Transcriptional regulation of the beta-casein gene by cytokines: cross-talk between STAT5 and other signaling molecules. \nThe beta-casein promoter has been widely used to monitor the activation of STAT (signal transducer and activator of transcription)5 since STAT5 was originally found as a mediator of PRL-inducible beta-casein expression. However, not only is expression of the beta-casein gene regulated by STAT5 but it is also affected by other molecules such as glucocorticoid and Ras. In this report, we describe the transcriptional regulation of the beta-casein gene by cytokines in T cells. We have found that the beta-casein gene is expressed in a cytotoxic T cell line, CTLL-2, in response to interleukin-2 (IL-2), which activates STAT5. While IL-4 does not activate STAT5, it induces expression of STAT5-regulated genes in CTLL-2, i.e. beta-casein, a cytokine-inducible SH2-containing protein (CIS), and oncostatin M (OSM), suggesting that STAT6 activated by IL-4 substitutes for the function of STAT5 in T cells. IL-2-induced beta-casein expression was enhanced by dexamethasone, and this synergistic effect of Dexamethasone requires the sequence between -155 and -193 in the beta-casein promoter. Coincidentally, a deletion of this region enhanced the IL-2-induced expression of beta-casein. Expression of an active form of Ras, Ras(G12V), suppressed the IL-2-induced beta-casein and OSM gene expression, and the negative effect of Ras is mediated by the region between -105 and -193 in the beta-casein promoter. In apparent contradiction, expression of a dominant negative form of Ras, RasN17, also inhibited IL-2-induced activation of the promoter containing the minimal beta-casein STAT5 element as well as the promoters of CIS and OSM. In addition, Ras(G12V) complemented signaling by an erythropoietin receptor mutant defective in Ras activation and augmented the activation of the beta-casein promoter by the mutant erythropoietin receptor signaling, suggesting a possible role of Ras in Stat5-mediated gene expression. These results collectively reveal a complex interaction of STAT5 with other signaling pathways and illustrate that regulation of gene expression requires integration of opposing signals. " ], "offsets": [ [ 0, 2227 ] ] } ]

[ { "id": "9817603_T1", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 34, 45 ] ], "normalized": [] }, { "id": "9817603_T2", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 84, 89 ] ], "normalized": [] }, { "id": "9817603_T3", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 126, 137 ] ], "normalized": [] }, { "id": "9817603_T4", "type": "Protein", "text": [ "STAT (signal transducer and activator of transcription)5" ], "offsets": [ [ 197, 253 ] ], "normalized": [] }, { "id": "9817603_T5", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 260, 265 ] ], "normalized": [] }, { "id": "9817603_T6", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 304, 307 ] ], "normalized": [] }, { "id": "9817603_T7", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 318, 329 ] ], "normalized": [] }, { "id": "9817603_T8", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 381, 392 ] ], "normalized": [] }, { "id": "9817603_T9", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 411, 416 ] ], "normalized": [] }, { "id": "9817603_T10", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 558, 569 ] ], "normalized": [] }, { "id": "9817603_T11", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 623, 634 ] ], "normalized": [] }, { "id": "9817603_T12", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 704, 717 ] ], "normalized": [] }, { "id": "9817603_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 719, 723 ] ], "normalized": [] }, { "id": "9817603_T14", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 742, 747 ] ], "normalized": [] }, { "id": "9817603_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 755, 759 ] ], "normalized": [] }, { "id": "9817603_T16", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 778, 783 ] ], "normalized": [] }, { "id": "9817603_T17", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "9817603_T18", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 848, 859 ] ], "normalized": [] }, { "id": "9817603_T19", "type": "Protein", "text": [ "cytokine-inducible SH2-containing protein" ], "offsets": [ [ 863, 904 ] ], "normalized": [] }, { "id": "9817603_T20", "type": "Protein", "text": [ "CIS" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "9817603_T21", "type": "Protein", "text": [ "oncostatin M" ], "offsets": [ [ 916, 928 ] ], "normalized": [] }, { "id": "9817603_T22", "type": "Protein", "text": [ "OSM" ], "offsets": [ [ 930, 933 ] ], "normalized": [] }, { "id": "9817603_T23", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 952, 957 ] ], "normalized": [] }, { "id": "9817603_T24", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 971, 975 ] ], "normalized": [] }, { "id": "9817603_T25", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 1008, 1013 ] ], "normalized": [] }, { "id": "9817603_T26", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1026, 1030 ] ], "normalized": [] }, { "id": "9817603_T27", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1039, 1050 ] ], "normalized": [] }, { "id": "9817603_T28", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1189, 1200 ] ], "normalized": [] }, { "id": "9817603_T29", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1266, 1270 ] ], "normalized": [] }, { "id": "9817603_T30", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1293, 1304 ] ], "normalized": [] }, { "id": "9817603_T31", "type": "Protein", "text": [ "Ras(G12V)" ], "offsets": [ [ 1343, 1352 ] ], "normalized": [] }, { "id": "9817603_T32", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1369, 1373 ] ], "normalized": [] }, { "id": "9817603_T33", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1382, 1393 ] ], "normalized": [] }, { "id": "9817603_T34", "type": "Protein", "text": [ "OSM" ], "offsets": [ [ 1398, 1401 ] ], "normalized": [] }, { "id": "9817603_T35", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1505, 1516 ] ], "normalized": [] }, { "id": "9817603_T36", "type": "Protein", "text": [ "RasN17" ], "offsets": [ [ 1601, 1607 ] ], "normalized": [] }, { "id": "9817603_T37", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1624, 1628 ] ], "normalized": [] }, { "id": "9817603_T38", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1687, 1698 ] ], "normalized": [] }, { "id": "9817603_T39", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 1699, 1704 ] ], "normalized": [] }, { "id": "9817603_T40", "type": "Protein", "text": [ "CIS" ], "offsets": [ [ 1741, 1744 ] ], "normalized": [] }, { "id": "9817603_T41", "type": "Protein", "text": [ "OSM" ], "offsets": [ [ 1749, 1752 ] ], "normalized": [] }, { "id": "9817603_T42", "type": "Protein", "text": [ "Ras(G12V)" ], "offsets": [ [ 1767, 1776 ] ], "normalized": [] }, { "id": "9817603_T43", "type": "Protein", "text": [ "erythropoietin receptor" ], "offsets": [ [ 1806, 1829 ] ], "normalized": [] }, { "id": "9817603_T44", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 1901, 1912 ] ], "normalized": [] }, { "id": "9817603_T45", "type": "Protein", "text": [ "erythropoietin receptor" ], "offsets": [ [ 1936, 1959 ] ], "normalized": [] }, { "id": "9817603_T46", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 2008, 2013 ] ], "normalized": [] }, { "id": "9817603_T47", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 2099, 2104 ] ], "normalized": [] }, { "id": "9817603_T49", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 138, 146 ] ], "normalized": [] }, { "id": "9817603_T69", "type": "Entity", "text": [ "sequence between -155 and -193" ], "offsets": [ [ 1151, 1181 ] ], "normalized": [] }, { "id": "9817603_T79", "type": "Entity", "text": [ "region between -105 and -193" ], "offsets": [ [ 1469, 1497 ] ], "normalized": [] }, { "id": "9817603_T84", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1913, 1921 ] ], "normalized": [] } ]

[ { "id": "9817603_E1", "type": "Regulation", "trigger": { "text": [ "Transcriptional regulation" ], "offsets": [ [ 0, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T1" } ] }, { "id": "9817603_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 183, 193 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T3" }, { "role": "Cause", "ref_id": "9817603_T4" }, { "role": "Site", "ref_id": "9817603_T49" } ] }, { "id": "9817603_E3", "type": "Positive_regulation", "trigger": { "text": [ "mediator" ], "offsets": [ [ 292, 300 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E4" }, { "role": "Cause", "ref_id": "9817603_T5" } ] }, { "id": "9817603_E4", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 308, 317 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E5" }, { "role": "Cause", "ref_id": "9817603_T6" } ] }, { "id": "9817603_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 330, 340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T7" } ] }, { "id": "9817603_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 363, 373 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T8" } ] }, { "id": "9817603_E7", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 398, 407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E6" }, { "role": "Cause", "ref_id": "9817603_T9" } ] }, { "id": "9817603_E8", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 432, 440 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E6" } ] }, { "id": "9817603_E9", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 524, 550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T10" } ] }, { "id": "9817603_E10", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 643, 652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T11" } ] }, { "id": "9817603_E11", "type": "Positive_regulation", "trigger": { "text": [ "in response" ], "offsets": [ [ 689, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E10" }, { "role": "Cause", "ref_id": "9817603_T13" } ] }, { "id": "9817603_E12", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 732, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T14" }, { "role": "Cause", "ref_id": "9817603_T13" } ] }, { "id": "9817603_E13", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 769, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T16" }, { "role": "Cause", "ref_id": "9817603_T15" } ] }, { "id": "9817603_E14", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 788, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E19" }, { "role": "Cause", "ref_id": "9817603_T15" } ] }, { "id": "9817603_E15", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 788, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E18" }, { "role": "Cause", "ref_id": "9817603_T15" } ] }, { "id": "9817603_E16", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 788, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E17" }, { "role": "Cause", "ref_id": "9817603_T15" } ] }, { "id": "9817603_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 796, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T22" } ] }, { "id": "9817603_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 796, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T18" } ] }, { "id": "9817603_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 796, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T20" } ] }, { "id": "9817603_E20", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 816, 825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T18" }, { "role": "Cause", "ref_id": "9817603_T17" } ] }, { "id": "9817603_E21", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 816, 825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T22" }, { "role": "Cause", "ref_id": "9817603_T17" } ] }, { "id": "9817603_E22", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 816, 825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T20" }, { "role": "Cause", "ref_id": "9817603_T17" } ] }, { "id": "9817603_E23", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 958, 967 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T23" }, { "role": "Cause", "ref_id": "9817603_T24" } ] }, { "id": "9817603_E24", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1031, 1038 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E25" }, { "role": "Cause", "ref_id": "9817603_T26" } ] }, { "id": "9817603_E25", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1051, 1061 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T27" } ] }, { "id": "9817603_E26", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1066, 1074 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E24" } ] }, { "id": "9817603_E27", "type": "Negative_regulation", "trigger": { "text": [ "deletion" ], "offsets": [ [ 1229, 1237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T28" }, { "role": "Site", "ref_id": "9817603_T69" } ] }, { "id": "9817603_E28", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1253, 1261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E29" }, { "role": "Cause", "ref_id": "9817603_E27" } ] }, { "id": "9817603_E29", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1271, 1278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E30" }, { "role": "Cause", "ref_id": "9817603_T29" } ] }, { "id": "9817603_E30", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1279, 1289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T30" } ] }, { "id": "9817603_E31", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 1306, 1316 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T31" } ] }, { "id": "9817603_E32", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 1354, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E35" }, { "role": "Cause", "ref_id": "9817603_E31" } ] }, { "id": "9817603_E33", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 1354, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E34" }, { "role": "Cause", "ref_id": "9817603_E31" } ] }, { "id": "9817603_E34", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1374, 1381 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E36" }, { "role": "Cause", "ref_id": "9817603_T32" } ] }, { "id": "9817603_E35", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1374, 1381 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E37" }, { "role": "Cause", "ref_id": "9817603_T32" } ] }, { "id": "9817603_E36", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1407, 1417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T33" } ] }, { "id": "9817603_E37", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1407, 1417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T34" } ] }, { "id": "9817603_E38", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1453, 1461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E33" }, { "role": "Cause", "ref_id": "9817603_T35" }, { "role": "CSite", "ref_id": "9817603_T79" } ] }, { "id": "9817603_E39", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1453, 1461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E32" }, { "role": "Cause", "ref_id": "9817603_T35" }, { "role": "CSite", "ref_id": "9817603_T79" } ] }, { "id": "9817603_E40", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1614, 1623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E42" }, { "role": "Cause", "ref_id": "9817603_T36" } ] }, { "id": "9817603_E41", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1614, 1623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E43" }, { "role": "Cause", "ref_id": "9817603_T36" } ] }, { "id": "9817603_E42", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1637, 1647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T40" }, { "role": "Cause", "ref_id": "9817603_T37" } ] }, { "id": "9817603_E43", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1637, 1647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T41" }, { "role": "Cause", "ref_id": "9817603_T37" } ] }, { "id": "9817603_E44", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 1869, 1878 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_E45" }, { "role": "Cause", "ref_id": "9817603_T42" } ] }, { "id": "9817603_E45", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1883, 1893 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T44" }, { "role": "Cause", "ref_id": "9817603_E46" }, { "role": "Site", "ref_id": "9817603_T84" } ] }, { "id": "9817603_E46", "type": "Regulation", "trigger": { "text": [ "signaling" ], "offsets": [ [ 1960, 1969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9817603_T45" } ] } ]

[ { "id": "9817603_1", "entity_ids": [ "9817603_T19", "9817603_T20" ] }, { "id": "9817603_2", "entity_ids": [ "9817603_T21", "9817603_T22" ] }, { "id": "9817603_3", "entity_ids": [ "9817603_T12", "9817603_T13" ] } ]

[]

[ { "id": "9634075__text", "type": "abstract", "text": [ "Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells. \nTuberculosis has emerged as an epidemic, extended by the large number of individuals infected with human immunodeficiency virus type 1 (HIV-1). The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M. tuberculosis) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system. These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals. Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it was first found that culture protein filtrates (CFP) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM. The implication of protein tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7. It was also determined, using electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally, the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha. The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection. " ], "offsets": [ [ 0, 1952 ] ] } ]

[ { "id": "9634075_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 658, 661 ] ], "normalized": [] }, { "id": "9634075_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1773, 1782 ] ], "normalized": [] } ]

[ { "id": "9634075_E1", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 662, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9634075_T1" } ] } ]

[]

[]

[ { "id": "9974401__text", "type": "abstract", "text": [ "Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet. \nBecause oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment. " ], "offsets": [ [ 0, 2218 ] ] } ]

[ { "id": "9974401_T1", "type": "Protein", "text": [ "interleukin (IL)-1alpha" ], "offsets": [ [ 599, 622 ] ], "normalized": [] }, { "id": "9974401_T2", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 624, 632 ] ], "normalized": [] }, { "id": "9974401_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 634, 638 ] ], "normalized": [] }, { "id": "9974401_T4", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 777, 810 ] ], "normalized": [] }, { "id": "9974401_T5", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 812, 818 ] ], "normalized": [] }, { "id": "9974401_T6", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 821, 831 ] ], "normalized": [] }, { "id": "9974401_T7", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 837, 870 ] ], "normalized": [] }, { "id": "9974401_T8", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 967, 973 ] ], "normalized": [] }, { "id": "9974401_T9", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1231, 1237 ] ], "normalized": [] }, { "id": "9974401_T10", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1445, 1451 ] ], "normalized": [] } ]

[ { "id": "9974401_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 763, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T6" } ] }, { "id": "9974401_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 763, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T7" } ] }, { "id": "9974401_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 763, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T5" } ] }, { "id": "9974401_E4", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 957, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T8" } ] }, { "id": "9974401_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1066, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_E9" } ] }, { "id": "9974401_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1066, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_E8" } ] }, { "id": "9974401_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1066, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_E10" } ] }, { "id": "9974401_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1080, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T5" } ] }, { "id": "9974401_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1080, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T6" } ] }, { "id": "9974401_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1080, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T7" } ] }, { "id": "9974401_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1238, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T9" } ] }, { "id": "9974401_E12", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1253, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_E11" } ] }, { "id": "9974401_E13", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1432, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9974401_T10" } ] } ]

[ { "id": "9974401_1", "entity_ids": [ "9974401_T4", "9974401_T5" ] } ]

[]

[ { "id": "7917514__text", "type": "abstract", "text": [ "Role of HIV-1 Nef expression in activation pathways in CD4+ T cells. \nThe role of the human immunodeficiency virus (HIV-1) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector. Secretion of IL-2 and TNF-alpha, surface expression of IL-2R, and DNA-binding activity of NF-kappa B and AP-1 (Fos/Jun) complex in response to phorbol myristate acetate, TNF-alpha, or immobilized antibodies to CD3 were monitored. These parameters were not modified by Nef expression in Jurkat cells, whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells. This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition. Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B-binding activity but through the region containing the negative responding elements (NREs). These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations. " ], "offsets": [ [ 0, 1193 ] ] } ]

[ { "id": "7917514_T1", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 14, 17 ] ], "normalized": [] }, { "id": "7917514_T2", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 55, 58 ] ], "normalized": [] }, { "id": "7917514_T3", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 123, 126 ] ], "normalized": [] }, { "id": "7917514_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 197, 200 ] ], "normalized": [] }, { "id": "7917514_T5", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 238, 241 ] ], "normalized": [] }, { "id": "7917514_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 274, 278 ] ], "normalized": [] }, { "id": "7917514_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 283, 292 ] ], "normalized": [] }, { "id": "7917514_T8", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 372, 375 ] ], "normalized": [] }, { "id": "7917514_T9", "type": "Protein", "text": [ "Jun" ], "offsets": [ [ 376, 379 ] ], "normalized": [] }, { "id": "7917514_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 431, 440 ] ], "normalized": [] }, { "id": "7917514_T11", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 529, 532 ] ], "normalized": [] }, { "id": "7917514_T12", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "7917514_T13", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "7917514_T14", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1062, 1065 ] ], "normalized": [] }, { "id": "7917514_T24", "type": "Entity", "text": [ "Thr-15" ], "offsets": [ [ 738, 744 ] ], "normalized": [] } ]

[ { "id": "7917514_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 18, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T1" } ] }, { "id": "7917514_E2", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 219, 230 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E3" } ] }, { "id": "7917514_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 242, 252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T5" } ] }, { "id": "7917514_E4", "type": "Localization", "trigger": { "text": [ "Secretion" ], "offsets": [ [ 261, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T6" } ] }, { "id": "7917514_E5", "type": "Localization", "trigger": { "text": [ "Secretion" ], "offsets": [ [ 261, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T7" } ] }, { "id": "7917514_E6", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 331, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T9" } ] }, { "id": "7917514_E7", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 331, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T8" } ] }, { "id": "7917514_E8", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E5" } ] }, { "id": "7917514_E9", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E7" } ] }, { "id": "7917514_E10", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E4" }, { "role": "Cause", "ref_id": "7917514_T10" } ] }, { "id": "7917514_E11", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E6" }, { "role": "Cause", "ref_id": "7917514_T10" } ] }, { "id": "7917514_E12", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E7" }, { "role": "Cause", "ref_id": "7917514_T10" } ] }, { "id": "7917514_E13", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E6" } ] }, { "id": "7917514_E14", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E5" }, { "role": "Cause", "ref_id": "7917514_T10" } ] }, { "id": "7917514_E15", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E4" } ] }, { "id": "7917514_E16", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E4" }, { "role": "Cause", "ref_id": "7917514_E20" } ] }, { "id": "7917514_E17", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E6" }, { "role": "Cause", "ref_id": "7917514_E20" } ] }, { "id": "7917514_E18", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E5" }, { "role": "Cause", "ref_id": "7917514_E20" } ] }, { "id": "7917514_E19", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_E7" }, { "role": "Cause", "ref_id": "7917514_E20" } ] }, { "id": "7917514_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 533, 543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T11" } ] }, { "id": "7917514_E21", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 719, 734 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T13" }, { "role": "Site", "ref_id": "7917514_T24" } ] }, { "id": "7917514_E22", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 752, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7917514_T13" } ] } ]

[]

[]

[ { "id": "9177217__text", "type": "abstract", "text": [ "Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5. \nTwo of the genes defective in the five complementation groups identified in the class II-negative bare lymphocyte syndrome or corresponding laboratory mutants have been cloned. One gene encodes a protein, RFX5, that is a member of the RFX family of DNA binding proteins. The other, CIITA, encodes a large protein with a defined acidic transcriptional activation domain; this protein does not interact with DNA. Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA binding domain activated transcription from a reporter construct containing GAL4 sites in a cotransfection assay in the Raji human B cell line. However, these plasmids produced transcriptional activity in HeLa cells only in conjunction with interferon gamma stimulation, a condition in which expression of both CIITA and class II major histocompatibility complex surface proteins are induced. Furthermore, these plasmids were not active in RJ2.2.5, an in vitro mutagenized derivative of Raji in which both copies of CIITA are defective. Transcriptional activation by the RFX5 fusion protein could be restored in RJ2.2.5 by cotransfection with a CIITA expression plasmid. Finally, a direct interaction between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western blot assays. Thus, RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA. " ], "offsets": [ [ 0, 1774 ] ] } ]

[ { "id": "9177217_T1", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "9177217_T2", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 109, 113 ] ], "normalized": [] }, { "id": "9177217_T3", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 321, 325 ] ], "normalized": [] }, { "id": "9177217_T4", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 398, 403 ] ], "normalized": [] }, { "id": "9177217_T5", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 567, 571 ] ], "normalized": [] }, { "id": "9177217_T6", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 585, 589 ] ], "normalized": [] }, { "id": "9177217_T7", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "9177217_T8", "type": "Protein", "text": [ "interferon gamma" ], "offsets": [ [ 835, 851 ] ], "normalized": [] }, { "id": "9177217_T9", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 905, 910 ] ], "normalized": [] }, { "id": "9177217_T10", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1110, 1115 ] ], "normalized": [] }, { "id": "9177217_T11", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1165, 1169 ] ], "normalized": [] }, { "id": "9177217_T12", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1239, 1244 ] ], "normalized": [] }, { "id": "9177217_T13", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1303, 1307 ] ], "normalized": [] }, { "id": "9177217_T14", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1312, 1317 ] ], "normalized": [] }, { "id": "9177217_T15", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1392, 1396 ] ], "normalized": [] }, { "id": "9177217_T16", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1449, 1454 ] ], "normalized": [] }, { "id": "9177217_T17", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1456, 1460 ] ], "normalized": [] }, { "id": "9177217_T18", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1465, 1470 ] ], "normalized": [] }, { "id": "9177217_T19", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1674, 1678 ] ], "normalized": [] }, { "id": "9177217_T20", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1767, 1772 ] ], "normalized": [] }, { "id": "9177217_T32", "type": "Entity", "text": [ "DNA binding domain" ], "offsets": [ [ 1652, 1670 ] ], "normalized": [] } ]

[ { "id": "9177217_E1", "type": "Binding", "trigger": { "text": [ "complex formation" ], "offsets": [ [ 9, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T1" }, { "role": "Theme", "ref_id": "9177217_T2" } ] }, { "id": "9177217_E2", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 133, 142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T1" } ] }, { "id": "9177217_E3", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 133, 142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T2" } ] }, { "id": "9177217_E4", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 508, 516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T4" } ] }, { "id": "9177217_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 886, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T9" } ] }, { "id": "9177217_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 978, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_E5" } ] }, { "id": "9177217_E7", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 1120, 1129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T10" } ] }, { "id": "9177217_E8", "type": "Positive_regulation", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1217, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_E9" } ] }, { "id": "9177217_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1245, 1255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T12" } ] }, { "id": "9177217_E10", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1283, 1294 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T13" }, { "role": "Theme", "ref_id": "9177217_T14" } ] }, { "id": "9177217_E11", "type": "Binding", "trigger": { "text": [ "associate to form a complex" ], "offsets": [ [ 1471, 1498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T17" }, { "role": "Theme", "ref_id": "9177217_T18" } ] }, { "id": "9177217_E12", "type": "Binding", "trigger": { "text": [ "specificity" ], "offsets": [ [ 1619, 1630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9177217_T19" }, { "role": "Site", "ref_id": "9177217_T32" } ] } ]

[]

[]

[ { "id": "10383397__text", "type": "abstract", "text": [ "3-deazaadenosine, a S-adenosylhomocysteine hydrolase inhibitor, has dual effects on NF-kappaB regulation. Inhibition of NF-kappaB transcriptional activity and promotion of IkappaBalpha degradation. \nPreviously we reported that 3-deazaadenosine (DZA), a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase inhibits bacterial lipopolysaccharide-induced transcription of tumor necrosis factor-alpha and interleukin-1beta in mouse macrophage RAW 264.7 cells. In this study, we demonstrate the effects of DZA on nuclear factor-kappaB (NF-kappaB) regulation. DZA inhibits the transcriptional activity of NF-kappaB through the hindrance of p65 (Rel-A) phosphorylation without reduction of its nuclear translocation and DNA binding activity. The inhibitory effect of DZA on NF-kappaB transcriptional activity is potentiated by the addition of homocysteine. Taken together, DZA promotes the proteolytic degradation of IkappaBalpha, but not IkappaBbeta, resulting in an increase of DNA binding activity of NF-kappaB in the nucleus in the absence of its transcriptional activity in RAW 264.7 cells. The reduction of IkappaBalpha by DZA is neither involved in IkappaB kinase complex activation nor modulated by the addition of homocysteine. This study strongly suggests that DZA may be a potent drug for the treatment of diseases in which NF-kappaB plays a central pathogenic role, as well as a useful tool for studying the regulation and physiological functions of NF-kappaB. " ], "offsets": [ [ 0, 1481 ] ] } ]

[ { "id": "10383397_T1", "type": "Protein", "text": [ "S-adenosylhomocysteine hydrolase" ], "offsets": [ [ 20, 52 ] ], "normalized": [] }, { "id": "10383397_T2", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 172, 184 ] ], "normalized": [] }, { "id": "10383397_T3", "type": "Protein", "text": [ "S-adenosylhomocysteine hydrolase" ], "offsets": [ [ 288, 320 ] ], "normalized": [] }, { "id": "10383397_T4", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 384, 411 ] ], "normalized": [] }, { "id": "10383397_T5", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 416, 433 ] ], "normalized": [] }, { "id": "10383397_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "10383397_T7", "type": "Protein", "text": [ "Rel-A" ], "offsets": [ [ 654, 659 ] ], "normalized": [] }, { "id": "10383397_T8", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 925, 937 ] ], "normalized": [] }, { "id": "10383397_T9", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 947, 958 ] ], "normalized": [] }, { "id": "10383397_T10", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1121, 1133 ] ], "normalized": [] } ]

[ { "id": "10383397_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 53, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T1" } ] }, { "id": "10383397_E2", "type": "Positive_regulation", "trigger": { "text": [ "promotion" ], "offsets": [ [ 159, 168 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E3" } ] }, { "id": "10383397_E3", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 185, 196 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T2" } ] }, { "id": "10383397_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 321, 329 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E5" } ] }, { "id": "10383397_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 359, 366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E7" } ] }, { "id": "10383397_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 359, 366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E8" } ] }, { "id": "10383397_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 367, 380 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T4" } ] }, { "id": "10383397_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 367, 380 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T5" } ] }, { "id": "10383397_E9", "type": "Negative_regulation", "trigger": { "text": [ "hindrance" ], "offsets": [ [ 636, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E10" } ] }, { "id": "10383397_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 661, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T7" } ] }, { "id": "10383397_E11", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 885, 893 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E14" } ] }, { "id": "10383397_E12", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 885, 893 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E13" } ] }, { "id": "10383397_E13", "type": "Protein_catabolism", "trigger": { "text": [ "proteolytic degradation" ], "offsets": [ [ 898, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T8" } ] }, { "id": "10383397_E14", "type": "Protein_catabolism", "trigger": { "text": [ "proteolytic degradation" ], "offsets": [ [ 898, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T9" } ] }, { "id": "10383397_E15", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1108, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_T10" } ] }, { "id": "10383397_E16", "type": "Regulation", "trigger": { "text": [ "modulated" ], "offsets": [ [ 1202, 1211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10383397_E15" } ] } ]

[ { "id": "10383397_1", "entity_ids": [ "10383397_T6", "10383397_T7" ] } ]

[]

[ { "id": "7594540__text", "type": "abstract", "text": [ "Nuclear factor-IL6 activates the human IL-4 promoter in T cells. \nPositive regulatory element I (PRE-I) is a strong enhancer element essential for expression of the human IL-4 gene. To identify transcription factors binding to PRE-I, we screened a cDNA expression library from Jurkat T cells and isolated a cDNA encoding nuclear factor (NF)-IL6 (also known as C/EBP beta). NF-IL6 mRNA was found in human Jurkat T cells and in the mouse Th2 clone D10, but not in Th1 clone 29. rNF-IL6 expressed in bacteria was shown to specifically bind to PRE-I. PRE-I forms multiple DNA-protein complexes with nuclear extracts from Jurkat cells. Some of these complexes were demonstrated to contain NF-IL6 by using anti-C/EBP beta Abs. Overexpression of NF-IL6 enhanced expression of the chloramphenicol acetyl transferase reporter gene linked to the PRE-I-thymidine kinase or the human IL-4 promoter more than 10-fold in Jurkat cells. Promoter deletion studies revealed two additional NF-IL6 binding sites located at positions -44 to -36 (C/EBP proximal) and -87 to -79 (C/EBP medial), respectively. Our results demonstrate that NF-IL6 is involved in transcriptional activation of the human IL-4 promoter in T cells. " ], "offsets": [ [ 0, 1203 ] ] } ]

[ { "id": "7594540_T1", "type": "Protein", "text": [ "Nuclear factor-IL6" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "7594540_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "7594540_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "7594540_T4", "type": "Protein", "text": [ "(NF)-IL6" ], "offsets": [ [ 336, 344 ] ], "normalized": [] }, { "id": "7594540_T5", "type": "Protein", "text": [ "C/EBP beta" ], "offsets": [ [ 360, 370 ] ], "normalized": [] }, { "id": "7594540_T6", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "7594540_T7", "type": "Protein", "text": [ "rNF-IL6" ], "offsets": [ [ 476, 483 ] ], "normalized": [] }, { "id": "7594540_T8", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 684, 690 ] ], "normalized": [] }, { "id": "7594540_T9", "type": "Protein", "text": [ "C/EBP beta" ], "offsets": [ [ 705, 715 ] ], "normalized": [] }, { "id": "7594540_T10", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 739, 745 ] ], "normalized": [] }, { "id": "7594540_T11", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 773, 807 ] ], "normalized": [] }, { "id": "7594540_T12", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 872, 876 ] ], "normalized": [] }, { "id": "7594540_T13", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 971, 977 ] ], "normalized": [] }, { "id": "7594540_T14", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 1115, 1121 ] ], "normalized": [] }, { "id": "7594540_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1177, 1181 ] ], "normalized": [] }, { "id": "7594540_T17", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 44, 52 ] ], "normalized": [] }, { "id": "7594540_T30", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1182, 1190 ] ], "normalized": [] } ]

[ { "id": "7594540_E1", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 19, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T2" }, { "role": "Cause", "ref_id": "7594540_T1" }, { "role": "Site", "ref_id": "7594540_T17" } ] }, { "id": "7594540_E2", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 133, 142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_E3" } ] }, { "id": "7594540_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 147, 157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T3" } ] }, { "id": "7594540_E4", "type": "Transcription", "trigger": { "text": [ "found" ], "offsets": [ [ 389, 394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T6" } ] }, { "id": "7594540_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 484, 493 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T7" } ] }, { "id": "7594540_E6", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 532, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T7" } ] }, { "id": "7594540_E7", "type": "Binding", "trigger": { "text": [ "complexes" ], "offsets": [ [ 645, 654 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T8" } ] }, { "id": "7594540_E8", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 721, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T10" } ] }, { "id": "7594540_E9", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 721, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_E8" } ] }, { "id": "7594540_E10", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 746, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_E11" }, { "role": "Cause", "ref_id": "7594540_E9" } ] }, { "id": "7594540_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 755, 765 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T11" } ] }, { "id": "7594540_E12", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1125, 1133 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_E13" }, { "role": "Cause", "ref_id": "7594540_T14" } ] }, { "id": "7594540_E13", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1137, 1163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7594540_T15" }, { "role": "Site", "ref_id": "7594540_T30" } ] } ]

[ { "id": "7594540_1", "entity_ids": [ "7594540_T4", "7594540_T5" ] } ]

[]

[ { "id": "7923175__text", "type": "abstract", "text": [ "T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report. \nRecent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in kappa B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins, the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 (p50) subunit. The second abnormality in kappa B-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-kappa B complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli. " ], "offsets": [ [ 0, 1469 ] ] } ]

[ { "id": "7923175_T1", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 960, 971 ] ], "normalized": [] }, { "id": "7923175_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "7923175_T3", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1077, 1081 ] ], "normalized": [] }, { "id": "7923175_T4", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1265, 1269 ] ], "normalized": [] }, { "id": "7923175_T8", "type": "Entity", "text": [ "nuclear extracts" ], "offsets": [ [ 1273, 1289 ] ], "normalized": [] } ]

[ { "id": "7923175_E1", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 863, 879 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7923175_T1" } ] }, { "id": "7923175_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1175, 1182 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7923175_T3" } ] }, { "id": "7923175_E3", "type": "Localization", "trigger": { "text": [ "detect" ], "offsets": [ [ 1254, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7923175_T4" }, { "role": "AtLoc", "ref_id": "7923175_T8" } ] } ]

[ { "id": "7923175_1", "entity_ids": [ "7923175_T1", "7923175_T2" ] } ]

[]

[ { "id": "8691127__text", "type": "abstract", "text": [ "Mechanisms of transactivation by nuclear factor of activated T cells-1. \nNuclear factor of activated T cells-family proteins (NFAT1/NFATp, NFATc, NFAT3, and NFAT4/NFATx/NFATc3) play a key role in the transcription of cytokine genes and other genes during the immune response. We have defined the mechanisms of transactivation by NFAT1. NFAT1 possesses two transactivation domains whose sequences are not conserved in the other NFAT-family proteins, and a conserved DNA-binding domain that mediates the recruitment of cooperating nuclear transcription factors even when it is expressed in the absence of other regions of the protein. The activity of the NH2-terminal transactivation domain is modulated by an adjacent regulatory region that contains several conserved sequence motifs represented only in the NFAT family. Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulated, and predict significant differences in the architecture of cooperative transcription complexes containing different NFAT-family proteins. " ], "offsets": [ [ 0, 1054 ] ] } ]

[ { "id": "8691127_T1", "type": "Protein", "text": [ "nuclear factor of activated T cells-1" ], "offsets": [ [ 33, 70 ] ], "normalized": [] }, { "id": "8691127_T2", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 126, 131 ] ], "normalized": [] }, { "id": "8691127_T3", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 132, 137 ] ], "normalized": [] }, { "id": "8691127_T4", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 139, 144 ] ], "normalized": [] }, { "id": "8691127_T5", "type": "Protein", "text": [ "NFAT3" ], "offsets": [ [ 146, 151 ] ], "normalized": [] }, { "id": "8691127_T6", "type": "Protein", "text": [ "NFAT4" ], "offsets": [ [ 157, 162 ] ], "normalized": [] }, { "id": "8691127_T7", "type": "Protein", "text": [ "NFATx" ], "offsets": [ [ 163, 168 ] ], "normalized": [] }, { "id": "8691127_T8", "type": "Protein", "text": [ "NFATc3" ], "offsets": [ [ 169, 175 ] ], "normalized": [] }, { "id": "8691127_T9", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 329, 334 ] ], "normalized": [] }, { "id": "8691127_T10", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 336, 341 ] ], "normalized": [] } ]

[ { "id": "8691127_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 575, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8691127_T10" } ] } ]

[ { "id": "8691127_1", "entity_ids": [ "8691127_T2", "8691127_T3" ] }, { "id": "8691127_2", "entity_ids": [ "8691127_T6", "8691127_T7", "8691127_T8" ] } ]

[]

[ { "id": "7542286__text", "type": "abstract", "text": [ "Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. \nTo test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall. " ], "offsets": [ [ 0, 1709 ] ] } ]

[ { "id": "7542286_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 402, 435 ] ], "normalized": [] }, { "id": "7542286_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 437, 443 ] ], "normalized": [] }, { "id": "7542286_T3", "type": "Protein", "text": [ "interleukin (IL)-1 alpha" ], "offsets": [ [ 496, 520 ] ], "normalized": [] }, { "id": "7542286_T4", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 532, 538 ] ], "normalized": [] }, { "id": "7542286_T5", "type": "Protein", "text": [ "IL-1 alpha" ], "offsets": [ [ 830, 840 ] ], "normalized": [] }, { "id": "7542286_T6", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 842, 851 ] ], "normalized": [] }, { "id": "7542286_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 853, 857 ] ], "normalized": [] }, { "id": "7542286_T8", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 859, 880 ] ], "normalized": [] }, { "id": "7542286_T9", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 882, 891 ] ], "normalized": [] }, { "id": "7542286_T10", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1011, 1021 ] ], "normalized": [] }, { "id": "7542286_T11", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 1046, 1079 ] ], "normalized": [] }, { "id": "7542286_T12", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1107, 1111 ] ], "normalized": [] }, { "id": "7542286_T13", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1116, 1120 ] ], "normalized": [] }, { "id": "7542286_T14", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1220, 1226 ] ], "normalized": [] }, { "id": "7542286_T15", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1265, 1271 ] ], "normalized": [] }, { "id": "7542286_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1342, 1348 ] ], "normalized": [] }, { "id": "7542286_T17", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1454, 1460 ] ], "normalized": [] } ]

[ { "id": "7542286_E1", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 363, 370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E3" } ] }, { "id": "7542286_E2", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 378, 387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E3" } ] }, { "id": "7542286_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 388, 398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T2" } ] }, { "id": "7542286_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 486, 495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E5" } ] }, { "id": "7542286_E5", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 521, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E6" }, { "role": "Cause", "ref_id": "7542286_T3" } ] }, { "id": "7542286_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 539, 549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T4" } ] }, { "id": "7542286_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E16" } ] }, { "id": "7542286_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E13" } ] }, { "id": "7542286_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E15" } ] }, { "id": "7542286_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E17" } ] }, { "id": "7542286_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E14" } ] }, { "id": "7542286_E12", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 741, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E4" } ] }, { "id": "7542286_E13", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E6" }, { "role": "Cause", "ref_id": "7542286_T9" } ] }, { "id": "7542286_E14", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E6" }, { "role": "Cause", "ref_id": "7542286_T7" } ] }, { "id": "7542286_E15", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E6" }, { "role": "Cause", "ref_id": "7542286_T5" } ] }, { "id": "7542286_E16", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E6" } ] }, { "id": "7542286_E17", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E6" }, { "role": "Cause", "ref_id": "7542286_T6" } ] }, { "id": "7542286_E18", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 935, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E24" } ] }, { "id": "7542286_E19", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 935, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E23" } ] }, { "id": "7542286_E20", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 935, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E22" } ] }, { "id": "7542286_E21", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 935, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E25" } ] }, { "id": "7542286_E22", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 961, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T10" } ] }, { "id": "7542286_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 961, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T12" } ] }, { "id": "7542286_E24", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 961, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T11" } ] }, { "id": "7542286_E25", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 961, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T13" } ] }, { "id": "7542286_E26", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1194, 1201 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E27" } ] }, { "id": "7542286_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1206, 1216 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T14" } ] }, { "id": "7542286_E28", "type": "Positive_regulation", "trigger": { "text": [ "augment" ], "offsets": [ [ 1240, 1247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E29" } ] }, { "id": "7542286_E29", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1257, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E30" } ] }, { "id": "7542286_E30", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1272, 1282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T15" } ] }, { "id": "7542286_E31", "type": "Negative_regulation", "trigger": { "text": [ "represses" ], "offsets": [ [ 1444, 1453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_E32" } ] }, { "id": "7542286_E32", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1466, 1479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7542286_T17" } ] } ]

[ { "id": "7542286_1", "entity_ids": [ "7542286_T8", "7542286_T9" ] }, { "id": "7542286_2", "entity_ids": [ "7542286_T1", "7542286_T2" ] } ]

[]

[ { "id": "8186461__text", "type": "abstract", "text": [ "Calcineurin potentiates activation of the granulocyte-macrophage colony-stimulating factor gene in T cells: involvement of the conserved lymphokine element 0. \nGranulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are produced by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in human T cell leukemia Jurkat cells. The expression of GM-CSF and IL-2 is inhibited by immunosuppressive drugs such as cyclosporin A (CsA) and FK506. Earlier studies on the IL-2 gene expression showed that overexpression of calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, can stimulate transcription from the IL-2 promoter through the NF-AT-binding site. In this study, we obtained evidence that transfection of the cDNAs for CN A (catalytic) and CN B (regulatory) subunits also augments transcription from the GM-CSF promoter and recovers the transcription inhibited by CsA. The constitutively active type of the CN A subunit, which lacks the auto-inhibitory and calmodulin-binding domains, acts in synergy with PMA to activate transcription from the GM-CSF promoter. We also found that the active CN partially replaces calcium ionophore in synergy with PMA to induce expression of endogenous GM-CSF and IL-2. By multimerizing the regulatory elements of the GM-CSF promoter, we found that one of the target sites for the CN action is the conserved lymphokine element 0 (CLE0), located at positions between -54 and -40. Mobility shift assays showed that the CLE0 sequence has an AP1-binding site and is associated with an NF-AT-like factor, termed NF-CLE0 gamma. NF-CLE0 gamma binding is induced by PMA/A23187 and is inhibited by treatment with CsA. These results suggest that CN is involved in the coordinated induction of the GM-CSF and IL-2 genes and that the CLE0 sequence of the GM-CSF gene is a functional analogue of the NF-AT-binding site in the IL-2 promoter, which mediates signals downstream of T cell activation. " ], "offsets": [ [ 0, 1988 ] ] } ]

[ { "id": "8186461_T1", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 42, 90 ] ], "normalized": [] }, { "id": "8186461_T2", "type": "Protein", "text": [ "Granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 160, 208 ] ], "normalized": [] }, { "id": "8186461_T3", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 210, 216 ] ], "normalized": [] }, { "id": "8186461_T4", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 222, 235 ] ], "normalized": [] }, { "id": "8186461_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 237, 241 ] ], "normalized": [] }, { "id": "8186461_T6", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 399, 405 ] ], "normalized": [] }, { "id": "8186461_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 410, 414 ] ], "normalized": [] }, { "id": "8186461_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 517, 521 ] ], "normalized": [] }, { "id": "8186461_T9", "type": "Protein", "text": [ "calmodulin" ], "offsets": [ [ 593, 603 ] ], "normalized": [] }, { "id": "8186461_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 672, 676 ] ], "normalized": [] }, { "id": "8186461_T11", "type": "Protein", "text": [ "CN A" ], "offsets": [ [ 789, 793 ] ], "normalized": [] }, { "id": "8186461_T12", "type": "Protein", "text": [ "CN B" ], "offsets": [ [ 810, 814 ] ], "normalized": [] }, { "id": "8186461_T13", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 874, 880 ] ], "normalized": [] }, { "id": "8186461_T14", "type": "Protein", "text": [ "CN A" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "8186461_T15", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1115, 1121 ] ], "normalized": [] }, { "id": "8186461_T16", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1257, 1263 ] ], "normalized": [] }, { "id": "8186461_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1268, 1272 ] ], "normalized": [] }, { "id": "8186461_T18", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1322, 1328 ] ], "normalized": [] }, { "id": "8186461_T19", "type": "Protein", "text": [ "NF-CLE0 gamma" ], "offsets": [ [ 1611, 1624 ] ], "normalized": [] }, { "id": "8186461_T20", "type": "Protein", "text": [ "NF-CLE0 gamma" ], "offsets": [ [ 1626, 1639 ] ], "normalized": [] }, { "id": "8186461_T21", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1791, 1797 ] ], "normalized": [] }, { "id": "8186461_T22", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "8186461_T23", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1847, 1853 ] ], "normalized": [] }, { "id": "8186461_T24", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1917, 1921 ] ], "normalized": [] } ]

[ { "id": "8186461_E1", "type": "Positive_regulation", "trigger": { "text": [ "potentiates" ], "offsets": [ [ 12, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E2" } ] }, { "id": "8186461_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 24, 34 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T1" } ] }, { "id": "8186461_E3", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 247, 255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T3" } ] }, { "id": "8186461_E4", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 247, 255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T5" } ] }, { "id": "8186461_E5", "type": "Positive_regulation", "trigger": { "text": [ "by stimulation with" ], "offsets": [ [ 256, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E3" } ] }, { "id": "8186461_E6", "type": "Positive_regulation", "trigger": { "text": [ "by stimulation with" ], "offsets": [ [ 256, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E4" } ] }, { "id": "8186461_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T7" } ] }, { "id": "8186461_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T6" } ] }, { "id": "8186461_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 418, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E8" } ] }, { "id": "8186461_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 418, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E7" } ] }, { "id": "8186461_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 527, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T8" } ] }, { "id": "8186461_E12", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 639, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E13" } ] }, { "id": "8186461_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 649, 662 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T10" } ] }, { "id": "8186461_E14", "type": "Positive_regulation", "trigger": { "text": [ "transfection" ], "offsets": [ [ 759, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E15" } ] }, { "id": "8186461_E15", "type": "Gene_expression", "trigger": { "text": [ "transfection" ], "offsets": [ [ 759, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T12" } ] }, { "id": "8186461_E16", "type": "Positive_regulation", "trigger": { "text": [ "transfection" ], "offsets": [ [ 759, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E17" } ] }, { "id": "8186461_E17", "type": "Gene_expression", "trigger": { "text": [ "transfection" ], "offsets": [ [ 759, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T11" } ] }, { "id": "8186461_E18", "type": "Positive_regulation", "trigger": { "text": [ "augments" ], "offsets": [ [ 842, 850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E20" }, { "role": "Cause", "ref_id": "8186461_E16" } ] }, { "id": "8186461_E19", "type": "Positive_regulation", "trigger": { "text": [ "augments" ], "offsets": [ [ 842, 850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E20" }, { "role": "Cause", "ref_id": "8186461_E14" } ] }, { "id": "8186461_E20", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 851, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T13" } ] }, { "id": "8186461_E21", "type": "Negative_regulation", "trigger": { "text": [ "recovers" ], "offsets": [ [ 894, 902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E23" }, { "role": "Cause", "ref_id": "8186461_E16" } ] }, { "id": "8186461_E22", "type": "Negative_regulation", "trigger": { "text": [ "recovers" ], "offsets": [ [ 894, 902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E23" }, { "role": "Cause", "ref_id": "8186461_E14" } ] }, { "id": "8186461_E23", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 921, 930 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E20" } ] }, { "id": "8186461_E24", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1083, 1091 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E25" } ] }, { "id": "8186461_E25", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1092, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T15" } ] }, { "id": "8186461_E26", "type": "Positive_regulation", "trigger": { "text": [ "to induce" ], "offsets": [ [ 1222, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E28" } ] }, { "id": "8186461_E27", "type": "Positive_regulation", "trigger": { "text": [ "to induce" ], "offsets": [ [ 1222, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E29" } ] }, { "id": "8186461_E28", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1232, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T17" } ] }, { "id": "8186461_E29", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1232, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T16" } ] }, { "id": "8186461_E30", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 1566, 1576 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T19" } ] }, { "id": "8186461_E31", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1640, 1647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T20" } ] }, { "id": "8186461_E32", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1651, 1658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E31" } ] }, { "id": "8186461_E33", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1680, 1689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_E31" } ] }, { "id": "8186461_E34", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1774, 1783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T22" } ] }, { "id": "8186461_E35", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1774, 1783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8186461_T21" } ] } ]

[ { "id": "8186461_1", "entity_ids": [ "8186461_T2", "8186461_T3" ] }, { "id": "8186461_2", "entity_ids": [ "8186461_T4", "8186461_T5" ] } ]

[]

[ { "id": "9741337__text", "type": "abstract", "text": [ "Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells. \nThe capacity of neonatal T cells to secrete interleukin-2 (IL-2) has been reported to be variable. We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester + calcium ionophore (PDBu + iono) or receptor-mediated anti-CD3/anti-CD3+ anti-CD28 stimulation. PDBu + iono induced equally high IL-2 levels in both groups and, when stimulated with plate-bound anti-CD3 monoclonal antibody (mAb), the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 (mean 331 +/- 86 pg/ml). The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types, but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells (respective mean values: 385 +/- 109 pg/ml and 4494 +/- 1199 pg/ml). As NF-kappa B is a critical transcription factor in the control of IL-2 expression, we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and, because induction of reactive oxygen intermediates (ROI) is required for the activation of NF-kappa B, we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry. In neonatal T cells NF-kappa B activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and, although addition of anti-CD28 mAb increased induction of NF-kappa B and ROI formation, levels similar to those of adults were not achieved. After PDBu + iono stimulation, the cells showed similar ROI formation and IL-2 secretion. Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3+ anti-CD28-mediated stimulation and that these activators cannot effectively activate the ROI-NF-kappa B signalling pathway in neonatal T cells. " ], "offsets": [ [ 0, 2016 ] ] } ]

[ { "id": "9741337_T1", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 8, 12 ] ], "normalized": [] }, { "id": "9741337_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 21, 34 ] ], "normalized": [] }, { "id": "9741337_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 177, 190 ] ], "normalized": [] }, { "id": "9741337_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 192, 196 ] ], "normalized": [] }, { "id": "9741337_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 244, 248 ] ], "normalized": [] }, { "id": "9741337_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 419, 423 ] ], "normalized": [] }, { "id": "9741337_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 470, 474 ] ], "normalized": [] }, { "id": "9741337_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 575, 579 ] ], "normalized": [] }, { "id": "9741337_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 665, 669 ] ], "normalized": [] }, { "id": "9741337_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 716, 720 ] ], "normalized": [] }, { "id": "9741337_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 773, 777 ] ], "normalized": [] }, { "id": "9741337_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "9741337_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1035, 1039 ] ], "normalized": [] }, { "id": "9741337_T14", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1559, 1563 ] ], "normalized": [] }, { "id": "9741337_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1748, 1752 ] ], "normalized": [] }, { "id": "9741337_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1797, 1801 ] ], "normalized": [] }, { "id": "9741337_T17", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1877, 1881 ] ], "normalized": [] } ]

[ { "id": "9741337_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 13, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E2" }, { "role": "Cause", "ref_id": "9741337_T1" } ] }, { "id": "9741337_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 35, 45 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T2" } ] }, { "id": "9741337_E3", "type": "Localization", "trigger": { "text": [ "secrete" ], "offsets": [ [ 169, 176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T4" } ] }, { "id": "9741337_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 249, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T5" } ] }, { "id": "9741337_E5", "type": "Regulation", "trigger": { "text": [ "using" ], "offsets": [ [ 299, 304 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E4" } ] }, { "id": "9741337_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 449, 456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T7" } ] }, { "id": "9741337_E7", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 580, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T8" } ] }, { "id": "9741337_E8", "type": "Negative_regulation", "trigger": { "text": [ "was undetectable" ], "offsets": [ [ 608, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E7" } ] }, { "id": "9741337_E9", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 641, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T9" } ] }, { "id": "9741337_E10", "type": "Negative_regulation", "trigger": { "text": [ "low amounts" ], "offsets": [ [ 650, 661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E9" } ] }, { "id": "9741337_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 763, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E12" } ] }, { "id": "9741337_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 778, 788 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T11" } ] }, { "id": "9741337_E13", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 1024, 1031 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E14" } ] }, { "id": "9741337_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1040, 1050 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T13" } ] }, { "id": "9741337_E15", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1753, 1762 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T15" } ] }, { "id": "9741337_E16", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1789, 1796 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E17" } ] }, { "id": "9741337_E17", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1802, 1812 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_T16" } ] }, { "id": "9741337_E18", "type": "Regulation", "trigger": { "text": [ "specific" ], "offsets": [ [ 1836, 1844 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9741337_E16" } ] } ]

[ { "id": "9741337_1", "entity_ids": [ "9741337_T3", "9741337_T4" ] } ]

[]

[ { "id": "7534663__text", "type": "abstract", "text": [ "Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells. \nBACKGROUND: The induction of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by tumor necrosis factor-alpha (TNF) is mediated by mobilization of the transcription factor nuclear factor-kappa B (NF-kappa B). Since salicylates have been reported to inhibit NF-kappa B activation by preventing the degradation of its inhibitor I kappa B, we studied a potential inhibition of this pathway by acetylsalicylate (aspirin) in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: Gel-shift analyses demonstrated dose-dependent inhibition of TNF-induced NF-kappa B mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L. Induction of VCAM-1 and E-selectin surface expression by TNF was dose-dependently reduced by aspirin over the same range, while induction of intercellular adhesion molecule-1 (ICAM-1) was hardly affected. Aspirin appeared to prevent VCAM-1 transcription, since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF. As a functional consequence, adhesion of U937 monocytes to TNF-stimulated HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and E-selectin upregulation. These effects of aspirin were not related to the inhibition of cyclooxygenase activity, since indomethacin was ineffective. CONCLUSIONS: Our data suggest that aspirin inhibits NF-kappa B mobilization, induction of VCAM-1 and E-selectin, and subsequent monocyte adhesion in endothelial cells stimulated by TNF, thereby providing an additional mechanism for therapeutic effects of aspirin. " ], "offsets": [ [ 0, 1651 ] ] } ]

[ { "id": "7534663_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 144, 177 ] ], "normalized": [] }, { "id": "7534663_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 179, 185 ] ], "normalized": [] }, { "id": "7534663_T3", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 191, 201 ] ], "normalized": [] }, { "id": "7534663_T4", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 205, 232 ] ], "normalized": [] }, { "id": "7534663_T5", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 234, 237 ] ], "normalized": [] }, { "id": "7534663_T6", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 674, 677 ] ], "normalized": [] }, { "id": "7534663_T7", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 781, 787 ] ], "normalized": [] }, { "id": "7534663_T8", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 792, 802 ] ], "normalized": [] }, { "id": "7534663_T9", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 825, 828 ] ], "normalized": [] }, { "id": "7534663_T10", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 909, 942 ] ], "normalized": [] }, { "id": "7534663_T11", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 944, 950 ] ], "normalized": [] }, { "id": "7534663_T12", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1001, 1007 ] ], "normalized": [] }, { "id": "7534663_T13", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1072, 1078 ] ], "normalized": [] }, { "id": "7534663_T14", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1087, 1090 ] ], "normalized": [] }, { "id": "7534663_T15", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "7534663_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1227, 1233 ] ], "normalized": [] }, { "id": "7534663_T17", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1238, 1248 ] ], "normalized": [] }, { "id": "7534663_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1477, 1483 ] ], "normalized": [] }, { "id": "7534663_T19", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1488, 1498 ] ], "normalized": [] }, { "id": "7534663_T20", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1568, 1571 ] ], "normalized": [] }, { "id": "7534663_T24", "type": "Entity", "text": [ "surface" ], "offsets": [ [ 803, 810 ] ], "normalized": [] } ]

[ { "id": "7534663_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 131, 140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T3" }, { "role": "Cause", "ref_id": "7534663_T5" } ] }, { "id": "7534663_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 131, 140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T2" }, { "role": "Cause", "ref_id": "7534663_T5" } ] }, { "id": "7534663_E3", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 242, 250 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E2" } ] }, { "id": "7534663_E4", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 242, 250 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E1" } ] }, { "id": "7534663_E5", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E8" }, { "role": "Cause", "ref_id": "7534663_T9" } ] }, { "id": "7534663_E6", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E7" }, { "role": "Cause", "ref_id": "7534663_T9" } ] }, { "id": "7534663_E7", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 811, 821 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T8" }, { "role": "AtLoc", "ref_id": "7534663_T24" } ] }, { "id": "7534663_E8", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 811, 821 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T7" }, { "role": "AtLoc", "ref_id": "7534663_T24" } ] }, { "id": "7534663_E9", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 850, 857 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E6" } ] }, { "id": "7534663_E10", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 850, 857 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E5" } ] }, { "id": "7534663_E11", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 896, 905 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T11" } ] }, { "id": "7534663_E12", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 963, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E11" } ] }, { "id": "7534663_E13", "type": "Negative_regulation", "trigger": { "text": [ "prevent" ], "offsets": [ [ 993, 1000 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E14" } ] }, { "id": "7534663_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1008, 1021 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T12" } ] }, { "id": "7534663_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1049, 1058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E16" } ] }, { "id": "7534663_E16", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1059, 1068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T13" }, { "role": "Cause", "ref_id": "7534663_T14" } ] }, { "id": "7534663_E17", "type": "Negative_regulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 1212, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E19" } ] }, { "id": "7534663_E18", "type": "Negative_regulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 1212, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E20" } ] }, { "id": "7534663_E19", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1249, 1261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T16" } ] }, { "id": "7534663_E20", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1249, 1261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T17" } ] }, { "id": "7534663_E21", "type": "Regulation", "trigger": { "text": [ "ineffective" ], "offsets": [ [ 1374, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E17" } ] }, { "id": "7534663_E22", "type": "Regulation", "trigger": { "text": [ "ineffective" ], "offsets": [ [ 1374, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E18" } ] }, { "id": "7534663_E23", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1430, 1438 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E25" } ] }, { "id": "7534663_E24", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1430, 1438 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_E26" } ] }, { "id": "7534663_E25", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1464, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T18" } ] }, { "id": "7534663_E26", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1464, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7534663_T19" } ] } ]

[ { "id": "7534663_1", "entity_ids": [ "7534663_T1", "7534663_T2" ] }, { "id": "7534663_2", "entity_ids": [ "7534663_T4", "7534663_T5" ] }, { "id": "7534663_3", "entity_ids": [ "7534663_T10", "7534663_T11" ] } ]

[]

[ { "id": "7931077__text", "type": "abstract", "text": [ "A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells. \nTwo groups of U937 promonocytic cells were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 (HIV-1) replication. \"Plus\" clones replicated the virus efficiently, whereas \"minus\" clones did not. We examined these clones for differences in nuclear factor (NF)-kappa B activity which might account for the observed phenomenon. Stimulation of plus clones liberated the classical p50-p65 complex from cytoplasmic pools, whereas minus clones produced an apparently novel, faster-migrating complex, as judged by electrophoretic mobility shift assays. It is surprising that the faster-migrating complex was composed also of p50 and p65. However, the p65 subunit was COOH-terminally truncated, as shown by immunoprecipitation. The truncation resulted from limited proteolysis of p65 during cellular extraction which released particular lysosomal serine proteases, such as elastase, cathepsin G, and proteinase 3. These specific proteases are coordinately expressed and were present exclusively in the minus U937 clones, but not in the plus clones, as demonstrated in the case of cathepsin G. In addition, these proteases were detected in certain subclones of THP-1 and HL-60 cells and in primary monocytes, in each case correlating with the truncated from of p65. We demonstrate in vitro cleavage of p65 by purified elastase and cathepsin G. It is possible that particular serine proteases may have inhibiting effects on the replication of HIV-1 in myelo-monocytic cells. The data also demonstrate that special precautions must be taken when making extracts from myelo-monocytic cells. " ], "offsets": [ [ 0, 1870 ] ] } ]

[ { "id": "7931077_T1", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 134, 137 ] ], "normalized": [] }, { "id": "7931077_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 668, 671 ] ], "normalized": [] }, { "id": "7931077_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 672, 675 ] ], "normalized": [] }, { "id": "7931077_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 909, 912 ] ], "normalized": [] }, { "id": "7931077_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 917, 920 ] ], "normalized": [] }, { "id": "7931077_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 935, 938 ] ], "normalized": [] }, { "id": "7931077_T7", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1063, 1066 ] ], "normalized": [] }, { "id": "7931077_T8", "type": "Protein", "text": [ "cathepsin G" ], "offsets": [ [ 1166, 1177 ] ], "normalized": [] }, { "id": "7931077_T9", "type": "Protein", "text": [ "proteinase 3" ], "offsets": [ [ 1183, 1195 ] ], "normalized": [] }, { "id": "7931077_T10", "type": "Protein", "text": [ "cathepsin G" ], "offsets": [ [ 1363, 1374 ] ], "normalized": [] }, { "id": "7931077_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1543, 1546 ] ], "normalized": [] }, { "id": "7931077_T12", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1584, 1587 ] ], "normalized": [] }, { "id": "7931077_T13", "type": "Protein", "text": [ "cathepsin G" ], "offsets": [ [ 1613, 1624 ] ], "normalized": [] } ]

[ { "id": "7931077_E1", "type": "Localization", "trigger": { "text": [ "liberated" ], "offsets": [ [ 644, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_T3" } ] }, { "id": "7931077_E2", "type": "Positive_regulation", "trigger": { "text": [ "liberated" ], "offsets": [ [ 644, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_E1" } ] }, { "id": "7931077_E3", "type": "Positive_regulation", "trigger": { "text": [ "liberated" ], "offsets": [ [ 644, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_E4" } ] }, { "id": "7931077_E4", "type": "Localization", "trigger": { "text": [ "liberated" ], "offsets": [ [ 644, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_T2" } ] }, { "id": "7931077_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1239, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_T8" } ] }, { "id": "7931077_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1239, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_T9" } ] }, { "id": "7931077_E7", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 1410, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_T8" } ] }, { "id": "7931077_E8", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 1410, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7931077_T9" } ] } ]

[]

[]

[ { "id": "9344365__text", "type": "abstract", "text": [ "Suppression of nuclear factor kappa B and CD18-mediated leukocyte adhesion to the corneal endothelium by dexamethasone. \nPURPOSE: To demonstrate that leukocyte adhesion to cultured corneal endothelial cells is mediated by the CD18 antigen, and to determine whether dexamethasone directly suppresses adhesion by inhibiting activation of nuclear factor kappa B (NFkappaB). METHODS: Cultured bovine corneal endothelium was stimulated for 6 hours by 40 micron/ml tumor necrosis factor alpha (TNFalpha). Dexamethasone was added 1 hour before TNFalpha stimulation in the dexamethasone group. After stimulation, neutrophils separated from a healthy human volunteer were added with or without anti-CD18 antibody. The culture plate was settled for 15 minutes at 37 degrees C, and then neutrophils were activated by N-formyl-methionyl-leucyl-phenylalanine for 5 minutes. Nonadherent neutrophils were removed by sealing and inverting the culture well. The intracellular localization of NFkappaB after TNFalpha simulation was determined by confocal immunocytochemistry using an anti-p65 antibody. RESULTS: Neutrophil adhesion to cultured corneal endothelial cells increased significantly on exposure to TNFalpha (451.4+/-45.4 cells/mm2, n = 16) compared to control (156.7+/-27.3 cells/mm2, n = 16, P < 0.01). This increased adhesion was suppressed by the addition of anti-CD18 antibody (157.6+/-25.1 cells/mm2, n = 8, P < 0.01) and by pretreatment with 10(-7) M dexamethasone (207.9+/-31.5 cells/mm2, n = 10, P < 0.01). Immunocytochemistry 60 minutes after stimulation revealed that NFkappaB was located in the cytoplasm in unstimulated cells; however, the addition of TNFalpha caused NFkappaB to translocate into the nucleus. Pretreatment with dexamethasone tapered NFkappaB translocation into the nucleus. CONCLUSIONS: Leukocyte adhesion to the corneal endothelium was shown to be mediated by CD18 expressed on activated leukocytes. Pretreatment of the endothelium with dexamethasone inhibited leukocyte adhesion; this may be due in part to the suppression of NFkappaB entry into the nucleus. " ], "offsets": [ [ 0, 2083 ] ] } ]

[ { "id": "9344365_T1", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "9344365_T2", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "9344365_T3", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 459, 486 ] ], "normalized": [] }, { "id": "9344365_T4", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 488, 496 ] ], "normalized": [] }, { "id": "9344365_T5", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 537, 545 ] ], "normalized": [] }, { "id": "9344365_T6", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 690, 694 ] ], "normalized": [] }, { "id": "9344365_T7", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 990, 998 ] ], "normalized": [] }, { "id": "9344365_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "9344365_T9", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1191, 1199 ] ], "normalized": [] }, { "id": "9344365_T10", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 1360, 1364 ] ], "normalized": [] }, { "id": "9344365_T11", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1657, 1665 ] ], "normalized": [] }, { "id": "9344365_T12", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 1883, 1887 ] ], "normalized": [] } ]

[ { "id": "9344365_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1888, 1897 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9344365_T12" } ] } ]

[ { "id": "9344365_1", "entity_ids": [ "9344365_T3", "9344365_T4" ] } ]

[]

[ { "id": "9882331__text", "type": "abstract", "text": [ "Human T-cell leukemia virus type 1 tax protein abrogates interleukin-2 dependence in a mouse T-cell line. \nHuman T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia. Tax, the viral protein, is thought to be crucial in the development of the disease, since it transforms healthy T cells in vitro and induces tumors in transgenic animals. We examined the effect of Tax activity on the growth of the interleukin-2 (IL-2)-dependent T-cell line CTLL-2. Stable expression of Tax in CTLL-2 transformed cell growth from being IL-2 dependent to IL-2 independent. Tax stimulated transcription through NF-kappaB and the cyclic AMP-responsive element-like sequence in the HTLV-1 promoter. The finding of Tax mutants segregating these two pathways suggested that the NF-kappaB pathway was essential for IL-2-independent growth of CTLL-2 cells while the CRE pathway was unnecessary. However, both pathways were necessary for another transformation-related activity (colony formation in soft agar) of CTLL-2/Tax. Our results show that Tax has at least two distinct activities on T cells, and suggest that Tax plays a crucial role in IL-2-independent T-cell transformation induced by HTLV-1, in addition to its well-known IL-2-dependent cell transformation. " ], "offsets": [ [ 0, 1276 ] ] } ]

[ { "id": "9882331_T1", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "9882331_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 57, 70 ] ], "normalized": [] }, { "id": "9882331_T3", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 200, 203 ] ], "normalized": [] }, { "id": "9882331_T4", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 397, 400 ] ], "normalized": [] }, { "id": "9882331_T5", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 431, 444 ] ], "normalized": [] }, { "id": "9882331_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 446, 450 ] ], "normalized": [] }, { "id": "9882331_T7", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 503, 506 ] ], "normalized": [] }, { "id": "9882331_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 552, 556 ] ], "normalized": [] }, { "id": "9882331_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "9882331_T10", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "9882331_T11", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 726, 729 ] ], "normalized": [] }, { "id": "9882331_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 824, 828 ] ], "normalized": [] }, { "id": "9882331_T13", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "9882331_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1054, 1057 ] ], "normalized": [] }, { "id": "9882331_T15", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "9882331_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1152, 1156 ] ], "normalized": [] }, { "id": "9882331_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1240, 1244 ] ], "normalized": [] } ]

[ { "id": "9882331_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 489, 499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9882331_T7" } ] } ]

[ { "id": "9882331_1", "entity_ids": [ "9882331_T5", "9882331_T6" ] } ]

[]

[ { "id": "7864072__text", "type": "abstract", "text": [ "Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. \nGlucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action. " ], "offsets": [ [ 0, 1332 ] ] } ]

[ { "id": "7864072_T1", "type": "Protein", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 442, 466 ] ], "normalized": [] }, { "id": "7864072_T2", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 468, 470 ] ], "normalized": [] }, { "id": "7864072_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 559, 568 ] ], "normalized": [] }, { "id": "7864072_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 570, 579 ] ], "normalized": [] }, { "id": "7864072_T5", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1063, 1065 ] ], "normalized": [] }, { "id": "7864072_T6", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1160, 1162 ] ], "normalized": [] }, { "id": "7864072_T8", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] } ]

[ { "id": "7864072_E1", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 271, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7864072_T2" } ] }, { "id": "7864072_E2", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1047, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7864072_T5" }, { "role": "AtLoc", "ref_id": "7864072_T8" } ] }, { "id": "7864072_E3", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1182, 1191 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7864072_T6" } ] } ]

[ { "id": "7864072_1", "entity_ids": [ "7864072_T1", "7864072_T2" ] } ]

[]

[ { "id": "10210321__text", "type": "abstract", "text": [ "Unexpected and coordinated expression of Spi-1, Fli-1, and megakaryocytic genes in four Epo-dependent cell lines established from transgenic mice displaying erythroid-specific expression of a thermosensitive SV40 T antigen. \nMost erythroleukemic cell lines established in vitro coexpress erythrocytic and megakaryocytic markers that often are associated with expression of Spi-1 and/or Fli-1 transcription factors known as transactivators of megakaryocyte-specific promoters. In the present study, we examined the possibility of establishing new cell lines keeping strictly erythroid-specific properties in vitro through the targeted and conditional immortalization of erythrocytic progenitors. For that purpose, we established several lines of transgenic mice displaying erythroid-specific expression of a thermosensitive SV40 T antigen. As expected, these transgenic mice developed splenomegaly due to the massive amplification of Ter 119 positive erythroid nucleated cells expressing T antigen. Despite this drastic effect in vivo, the in vitro immortalization of erythropoietin-dependent erythroid progenitors unexpectedly occurred at low frequency, and all four cell lines established expressed both erythrocytic (globins) and megakaryocytic markers (glycoprotein IIb, platelet factor 4) as well as Spi-1 and Fli-1 transcripts at permissive temperature. Switching the cells to the nonpermissive temperature led to a marked increase in globin gene expression and concomitant decrease in expression of Spi-1, Fli-1, and megakaryocytic genes in an erythropoietin-dependent manner. Interestingly, enhanced expression of Spi-1 and Fli-1 genes already was detected in the Ter 119 positive cell population of transgenic mice spleen in vivo. However, like normal Ter 119 erythroid cells, these Ter 119 positive cells from transgenic mice still expressed high levels of beta-globin and very low or undetectable glycoprotein IIb and platelet factor 4 megakaryocytic transcripts. Taken together, these data indicate that the unexpected expression of megakaryocytic genes is a specific property of immortalized cells that cannot be explained only by enhanced expression of Spi-1 and/or Fli-1 genes. " ], "offsets": [ [ 0, 2192 ] ] } ]

[ { "id": "10210321_T1", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 41, 46 ] ], "normalized": [] }, { "id": "10210321_T2", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 48, 53 ] ], "normalized": [] }, { "id": "10210321_T3", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "10210321_T4", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 373, 378 ] ], "normalized": [] }, { "id": "10210321_T5", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 386, 391 ] ], "normalized": [] }, { "id": "10210321_T6", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 1067, 1081 ] ], "normalized": [] }, { "id": "10210321_T7", "type": "Protein", "text": [ "glycoprotein IIb" ], "offsets": [ [ 1256, 1272 ] ], "normalized": [] }, { "id": "10210321_T8", "type": "Protein", "text": [ "platelet factor 4" ], "offsets": [ [ 1274, 1291 ] ], "normalized": [] }, { "id": "10210321_T9", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1304, 1309 ] ], "normalized": [] }, { "id": "10210321_T10", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "10210321_T11", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1505, 1510 ] ], "normalized": [] }, { "id": "10210321_T12", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 1512, 1517 ] ], "normalized": [] }, { "id": "10210321_T13", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 1550, 1564 ] ], "normalized": [] }, { "id": "10210321_T14", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1621, 1626 ] ], "normalized": [] }, { "id": "10210321_T15", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 1631, 1636 ] ], "normalized": [] }, { "id": "10210321_T16", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1866, 1877 ] ], "normalized": [] }, { "id": "10210321_T17", "type": "Protein", "text": [ "glycoprotein IIb" ], "offsets": [ [ 1907, 1923 ] ], "normalized": [] }, { "id": "10210321_T18", "type": "Protein", "text": [ "platelet factor 4" ], "offsets": [ [ 1928, 1945 ] ], "normalized": [] }, { "id": "10210321_T19", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 2166, 2171 ] ], "normalized": [] }, { "id": "10210321_T20", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 2179, 2184 ] ], "normalized": [] } ]

[ { "id": "10210321_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 27, 37 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T2" } ] }, { "id": "10210321_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 27, 37 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T1" } ] }, { "id": "10210321_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 359, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T4" } ] }, { "id": "10210321_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 359, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T5" } ] }, { "id": "10210321_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1190, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T7" } ] }, { "id": "10210321_E6", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1190, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T9" } ] }, { "id": "10210321_E7", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1190, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T10" } ] }, { "id": "10210321_E8", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1190, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T8" } ] }, { "id": "10210321_E9", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1479, 1487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_E12" } ] }, { "id": "10210321_E10", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1479, 1487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_E11" } ] }, { "id": "10210321_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1491, 1501 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T11" } ] }, { "id": "10210321_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1491, 1501 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T12" } ] }, { "id": "10210321_E13", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1565, 1574 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_E9" }, { "role": "Cause", "ref_id": "10210321_T13" } ] }, { "id": "10210321_E14", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1565, 1574 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_E10" }, { "role": "Cause", "ref_id": "10210321_T13" } ] }, { "id": "10210321_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1607, 1617 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T15" } ] }, { "id": "10210321_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1607, 1617 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T14" } ] }, { "id": "10210321_E17", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1841, 1850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T18" } ] }, { "id": "10210321_E18", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1841, 1850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T17" } ] }, { "id": "10210321_E19", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1841, 1850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T16" } ] }, { "id": "10210321_E20", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 2143, 2151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_E22" } ] }, { "id": "10210321_E21", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 2143, 2151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_E23" } ] }, { "id": "10210321_E22", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2152, 2162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T19" } ] }, { "id": "10210321_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2152, 2162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10210321_T20" } ] } ]

[]

[]

[ { "id": "10349513__text", "type": "abstract", "text": [ "Targeted remodeling of human beta-globin promoter chromatin structure produces increased expression and decreased silencing. \nThe chromatin structure of the human beta-globin gene locus assumes a transcriptionally-active conformation in erythroid cells. One feature of this chromatin reorganization is the formation of DNase 1 hypersensitive sites in the regions of active globin gene promoters. This reorganization requires the globin locus control region and is associated with normal expression of the beta-like globin genes. To determine whether it is possible to artificially enhance the opening of the chromatin structure of a minimal beta-globin promoter, we placed a 101bp, erythroid-specific DNase 1 hypersensitive site-forming element (HSFE) immediately upstream of the beta-globin promoter and gene. This element includes binding sites for NF-E2, AP-1, GATA-1 and Sp-1. Constructs were stably transfected into murine erythroleukemia cells and promoter chromatin structure and gene expression were analyzed. The HSFE induced an area of enhanced DNase 1 hypersensitivity extending from the transcriptional start site to -300bp of the artificial promoter and significantly increased the proportion of beta-globin promoters in an open chromatin configuration. This remodeling of promoter chromatin structure resulted in 3-fold increases in beta-globin gene transcription and induction, and inhibited long-term beta-globin gene silencing. These results indicate that a relatively small cis-acting element is able to enhance remodeling of promoter chromatin structure resulting in increased beta-globin gene expression. " ], "offsets": [ [ 0, 1625 ] ] } ]

[ { "id": "10349513_T1", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 29, 40 ] ], "normalized": [] }, { "id": "10349513_T2", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 163, 174 ] ], "normalized": [] }, { "id": "10349513_T3", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 641, 652 ] ], "normalized": [] }, { "id": "10349513_T4", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 780, 791 ] ], "normalized": [] }, { "id": "10349513_T5", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 864, 870 ] ], "normalized": [] }, { "id": "10349513_T6", "type": "Protein", "text": [ "Sp-1" ], "offsets": [ [ 875, 879 ] ], "normalized": [] }, { "id": "10349513_T7", "type": "Protein", "text": [ "DNase 1" ], "offsets": [ [ 1055, 1062 ] ], "normalized": [] }, { "id": "10349513_T8", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1209, 1220 ] ], "normalized": [] }, { "id": "10349513_T9", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1347, 1358 ] ], "normalized": [] }, { "id": "10349513_T10", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1417, 1428 ] ], "normalized": [] }, { "id": "10349513_T11", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1596, 1607 ] ], "normalized": [] }, { "id": "10349513_T16", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 1221, 1230 ] ], "normalized": [] } ]

[ { "id": "10349513_E1", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 79, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_E2" } ] }, { "id": "10349513_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 89, 99 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_T1" } ] }, { "id": "10349513_E3", "type": "Transcription", "trigger": { "text": [ "transcriptionally-active" ], "offsets": [ [ 196, 220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_T2" } ] }, { "id": "10349513_E4", "type": "Positive_regulation", "trigger": { "text": [ "increased the proportion" ], "offsets": [ [ 1181, 1205 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_T8" }, { "role": "Site", "ref_id": "10349513_T16" } ] }, { "id": "10349513_E5", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1334, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_E8" } ] }, { "id": "10349513_E6", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1334, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_E7" } ] }, { "id": "10349513_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1364, 1377 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_T9" } ] }, { "id": "10349513_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1382, 1391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_T9" } ] }, { "id": "10349513_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1586, 1595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_E10" } ] }, { "id": "10349513_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1613, 1623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10349513_T11" } ] } ]

[]

[]

[ { "id": "8796372__text", "type": "abstract", "text": [ "Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging. \nTranscription factor NF kappa B (nuclear factor kappa B) is induced in T lymphocytes from young individuals following activation with a variety of stimuli including anti-CD3, phorbol myristate acetate (PMA), and tumor necrosis factor-alpha (TNF-alpha). In contrast, activated T lymphocytes from older individuals show a significant reduction in the induction of NF kappa B in response to the same stimuli. The age-related decline in induction of NF kappa B could not be attributed to alteration in the composition of subunits, p50 and p65 were found to be the predominant subunits of induced NF kappa B in T cells from young as well as elderly donors. Furthermore, similar levels of NF kappa B were found in the cytosols of unactivated T cells from both young and elderly donors suggesting that precursor levels of NF kappa B remain unaltered during aging. These results suggest that an age-associated decline in the induction of NF kappa B in activated T cells from elderly individuals may be attributable to altered regulation of the inhibitor, I kappa B, and may play an important role in immune dysregulation accompanying aging. " ], "offsets": [ [ 0, 1238 ] ] } ]

[ { "id": "8796372_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 317, 344 ] ], "normalized": [] }, { "id": "8796372_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 346, 355 ] ], "normalized": [] }, { "id": "8796372_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 632, 635 ] ], "normalized": [] }, { "id": "8796372_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 640, 643 ] ], "normalized": [] } ]

[ { "id": "8796372_E1", "type": "Positive_regulation", "trigger": { "text": [ "be the predominant subunits" ], "offsets": [ [ 658, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8796372_T4" } ] }, { "id": "8796372_E2", "type": "Gene_expression", "trigger": { "text": [ "be the predominant subunits" ], "offsets": [ [ 658, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8796372_T3" } ] }, { "id": "8796372_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 689, 696 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8796372_T4" } ] }, { "id": "8796372_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 689, 696 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8796372_T3" } ] } ]

[ { "id": "8796372_1", "entity_ids": [ "8796372_T1", "8796372_T2" ] } ]

[]

[ { "id": "7670114__text", "type": "abstract", "text": [ "The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines. \nPU.1 is a hematopoietic transcription factor belonging to the Ets-family. It is identical to the Spi-1 oncogene, which is implicated in spleen focus-forming virus-induced murine erythroleukemias. PU.1 seems to be required for early development of multiple hematopoietic lineages, but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage-differentiation lineage. It binds the so-called Pu box, an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages. We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells. PU.1 mRNA expression and PU.1 DNA binding activity, as measured by Northern blot analysis and electrophoretic mobility shift assay, respectively, were evident in cell lines representing pro-B, pre-B, and mature B cells. We could also show Pu box-dependent transactivation of a reporter gene in transient transfections in these cell lines. In contrast, in a number of multiple myeloma cell lines, representing differentiated, plasma cell-like B cells, PU.1 DNA binding activity, mRNA expression, and Pu box-dependent transactivation were absent or detectable at a very low level. In lymphoblastoid cell lines, which exemplify an intermediate stage of B-cell differentiation, a reduced expression and activity were observed. The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines. At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells. " ], "offsets": [ [ 0, 2108 ] ] } ]

[ { "id": "7670114_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "7670114_T2", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 100, 104 ] ], "normalized": [] }, { "id": "7670114_T3", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 197, 202 ] ], "normalized": [] }, { "id": "7670114_T4", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 296, 300 ] ], "normalized": [] }, { "id": "7670114_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "7670114_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 874, 878 ] ], "normalized": [] }, { "id": "7670114_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 899, 903 ] ], "normalized": [] }, { "id": "7670114_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1325, 1329 ] ], "normalized": [] }, { "id": "7670114_T9", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1710, 1714 ] ], "normalized": [] }, { "id": "7670114_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1795, 1799 ] ], "normalized": [] }, { "id": "7670114_T11", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1898, 1902 ] ], "normalized": [] } ]

[ { "id": "7670114_E1", "type": "Negative_regulation", "trigger": { "text": [ "downregulated" ], "offsets": [ [ 47, 60 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T1" } ] }, { "id": "7670114_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 388, 398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T4" } ] }, { "id": "7670114_E3", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 517, 522 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T4" } ] }, { "id": "7670114_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 681, 691 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T5" } ] }, { "id": "7670114_E5", "type": "Positive_regulation", "trigger": { "text": [ "activity" ], "offsets": [ [ 696, 704 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T5" } ] }, { "id": "7670114_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 884, 894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T6" } ] }, { "id": "7670114_E7", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 908, 924 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T7" } ] }, { "id": "7670114_E8", "type": "Negative_regulation", "trigger": { "text": [ "absent or detectable at a very low level" ], "offsets": [ [ 1411, 1451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E6" } ] }, { "id": "7670114_E9", "type": "Negative_regulation", "trigger": { "text": [ "absent or detectable at a very low level" ], "offsets": [ [ 1411, 1451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E7" } ] }, { "id": "7670114_E10", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1550, 1557 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E12" } ] }, { "id": "7670114_E11", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1550, 1557 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E13" } ] }, { "id": "7670114_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1558, 1568 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T8" } ] }, { "id": "7670114_E13", "type": "Positive_regulation", "trigger": { "text": [ "activity" ], "offsets": [ [ 1573, 1581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T8" } ] }, { "id": "7670114_E14", "type": "Negative_regulation", "trigger": { "text": [ "downregulated" ], "offsets": [ [ 1696, 1709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E15" } ] }, { "id": "7670114_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1715, 1725 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T9" } ] }, { "id": "7670114_E16", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1803, 1812 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T10" } ] }, { "id": "7670114_E17", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 1817, 1823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T10" } ] }, { "id": "7670114_E18", "type": "Negative_regulation", "trigger": { "text": [ "lack" ], "offsets": [ [ 1890, 1894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E21" } ] }, { "id": "7670114_E19", "type": "Negative_regulation", "trigger": { "text": [ "lack" ], "offsets": [ [ 1890, 1894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E20" } ] }, { "id": "7670114_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1903, 1913 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T11" } ] }, { "id": "7670114_E21", "type": "Positive_regulation", "trigger": { "text": [ "activity" ], "offsets": [ [ 1918, 1926 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_T11" } ] }, { "id": "7670114_E22", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 1988, 1998 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E18" } ] }, { "id": "7670114_E23", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 1988, 1998 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E19" } ] }, { "id": "7670114_E24", "type": "Regulation", "trigger": { "text": [ "developmental regulation" ], "offsets": [ [ 2045, 2069 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E19" } ] }, { "id": "7670114_E25", "type": "Regulation", "trigger": { "text": [ "developmental regulation" ], "offsets": [ [ 2045, 2069 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7670114_E18" } ] } ]

[]

[]

[ { "id": "7589085__text", "type": "abstract", "text": [ "CD30 ligation induces nuclear factor-kappa B activation in human T cell lines. \nCD30 is a recently described member of the tumor necrosis factor/nerve growth factor receptor superfamily. In this report, we show that following incubation of L540 cells (Hodgkin's disease-derived, T cell-like, CD30+ cells) with the agonistic anti-CD30 monoclonal antibodies (mAb) M44 and M67, two nuclear factor (NF)-kappa B DNA binding activities were induced in nuclear extracts, as determined in gel retardation assays. The effect of the mAb towards NF-kappa B activation was rapid, as it occurred within 20 min, and was sustained for up to 6 h. By comparison, an isotype-matched antibody had no effect on NF-kappa B activation. Moreover, in human T helper (Th) clones functionally characterized as being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively), the extent of CD30-mediated NF-kappa B activation correlated with the proportion of CD30+ cells. In all cell lines investigated, the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1, p65 RelA, and possibly other transcription factors. Collectively, our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation. " ], "offsets": [ [ 0, 1316 ] ] } ]

[ { "id": "7589085_T1", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "7589085_T2", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 80, 84 ] ], "normalized": [] }, { "id": "7589085_T3", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 292, 296 ] ], "normalized": [] }, { "id": "7589085_T4", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 329, 333 ] ], "normalized": [] }, { "id": "7589085_T5", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 878, 882 ] ], "normalized": [] }, { "id": "7589085_T6", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 948, 952 ] ], "normalized": [] }, { "id": "7589085_T7", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 1036, 1040 ] ], "normalized": [] }, { "id": "7589085_T8", "type": "Protein", "text": [ "p50 NF-kappa B1" ], "offsets": [ [ 1074, 1089 ] ], "normalized": [] }, { "id": "7589085_T9", "type": "Protein", "text": [ "p65 RelA" ], "offsets": [ [ 1091, 1099 ] ], "normalized": [] }, { "id": "7589085_T10", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 1301, 1305 ] ], "normalized": [] } ]

[ { "id": "7589085_E1", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 5, 13 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7589085_T1" } ] }, { "id": "7589085_E2", "type": "Binding", "trigger": { "text": [ "engagement" ], "offsets": [ [ 1041, 1051 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7589085_T7" } ] }, { "id": "7589085_E3", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 1306, 1314 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7589085_T10" } ] } ]

[]

[]

[ { "id": "2237444__text", "type": "abstract", "text": [ "Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. \nAlteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects. " ], "offsets": [ [ 0, 1509 ] ] } ]

[ { "id": "2237444_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1210, 1223 ] ], "normalized": [] }, { "id": "2237444_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1225, 1229 ] ], "normalized": [] }, { "id": "2237444_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "2237444_T6", "type": "Entity", "text": [ "mutated octamer site" ], "offsets": [ [ 1285, 1305 ] ], "normalized": [] } ]

[ { "id": "2237444_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1200, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2237444_E3" }, { "role": "Cause", "ref_id": "2237444_T3" }, { "role": "CSite", "ref_id": "2237444_T6" } ] }, { "id": "2237444_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1200, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2237444_E3" } ] }, { "id": "2237444_E3", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1231, 1240 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2237444_T2" } ] } ]

[ { "id": "2237444_1", "entity_ids": [ "2237444_T1", "2237444_T2" ] } ]

[]

[ { "id": "9722600__text", "type": "abstract", "text": [ "Activation of E2F-mediated transcription by human T-cell leukemia virus type I Tax protein in a p16(INK4A)-negative T-cell line. \nThe human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia. Although the exact mechanism by which HTLV-I contributes to leukemogenesis is still unclear, the Tax protein is thought to play a major role in this process. This 40-kDa polypeptide is able to interact with the tumor suppressor p16(INK4A). Consequently, Tax can activate the signaling pathway that lead to the release of E2F that in turn induces expression of factors required for cell cycle progression. In this paper, we demonstrate that Tax can also activate E2F-mediated transcription independently of p16(INK4A). Indeed, when Tax is coexpressed with the E2F-1 transcription factor in CEM T-cells, which lack expression of p16(INK4A), it strongly potentiates the E2F-dependent activation of a reporter construct driven by a promoter containing E2F binding sites. This stimulation is abrogated by mutations affecting the E2F-binding sites. In addition, Tax also stimulates the transcription of the E2F-1 gene itself. Using Tax mutants that fail to activate either ATF- or NF-kappaB-dependent promoters and different 5' truncation mutants of the E2F-1 promoter, we show that the Tax-dependent transcriptional control of the E2F1 gene involves, at least in part, the ATF binding site located in the E2F-1 promoter. " ], "offsets": [ [ 0, 1441 ] ] } ]

[ { "id": "9722600_T1", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 79, 82 ] ], "normalized": [] }, { "id": "9722600_T2", "type": "Protein", "text": [ "p16" ], "offsets": [ [ 96, 99 ] ], "normalized": [] }, { "id": "9722600_T3", "type": "Protein", "text": [ "INK4A" ], "offsets": [ [ 100, 105 ] ], "normalized": [] }, { "id": "9722600_T4", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 322, 325 ] ], "normalized": [] }, { "id": "9722600_T5", "type": "Protein", "text": [ "p16" ], "offsets": [ [ 453, 456 ] ], "normalized": [] }, { "id": "9722600_T6", "type": "Protein", "text": [ "INK4A" ], "offsets": [ [ 457, 462 ] ], "normalized": [] }, { "id": "9722600_T7", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 479, 482 ] ], "normalized": [] }, { "id": "9722600_T8", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 665, 668 ] ], "normalized": [] }, { "id": "9722600_T9", "type": "Protein", "text": [ "p16" ], "offsets": [ [ 731, 734 ] ], "normalized": [] }, { "id": "9722600_T10", "type": "Protein", "text": [ "INK4A" ], "offsets": [ [ 735, 740 ] ], "normalized": [] }, { "id": "9722600_T11", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 756, 759 ] ], "normalized": [] }, { "id": "9722600_T12", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 784, 789 ] ], "normalized": [] }, { "id": "9722600_T13", "type": "Protein", "text": [ "p16" ], "offsets": [ [ 852, 855 ] ], "normalized": [] }, { "id": "9722600_T14", "type": "Protein", "text": [ "INK4A" ], "offsets": [ [ 856, 861 ] ], "normalized": [] }, { "id": "9722600_T15", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1081, 1084 ] ], "normalized": [] }, { "id": "9722600_T16", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 1126, 1131 ] ], "normalized": [] }, { "id": "9722600_T17", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "9722600_T18", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 1273, 1278 ] ], "normalized": [] }, { "id": "9722600_T19", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1306, 1309 ] ], "normalized": [] }, { "id": "9722600_T20", "type": "Protein", "text": [ "E2F1" ], "offsets": [ [ 1351, 1355 ] ], "normalized": [] }, { "id": "9722600_T21", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 1425, 1430 ] ], "normalized": [] }, { "id": "9722600_T28", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1279, 1287 ] ], "normalized": [] } ]

[ { "id": "9722600_E1", "type": "Gene_expression", "trigger": { "text": [ "negative" ], "offsets": [ [ 107, 115 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_T3" } ] }, { "id": "9722600_E2", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 418, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_T4" }, { "role": "Theme", "ref_id": "9722600_T6" } ] }, { "id": "9722600_E3", "type": "Gene_expression", "trigger": { "text": [ "coexpressed" ], "offsets": [ [ 763, 774 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_T11" } ] }, { "id": "9722600_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 1090, 1100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_E5" }, { "role": "Cause", "ref_id": "9722600_T15" } ] }, { "id": "9722600_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1105, 1118 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_T16" } ] }, { "id": "9722600_E6", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1176, 1184 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_T18" }, { "role": "Cause", "ref_id": "9722600_T17" }, { "role": "Site", "ref_id": "9722600_T28" } ] }, { "id": "9722600_E7", "type": "Regulation", "trigger": { "text": [ "transcriptional control" ], "offsets": [ [ 1320, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9722600_T20" }, { "role": "Cause", "ref_id": "9722600_T19" } ] } ]

[]

[]

[ { "id": "9095577__text", "type": "abstract", "text": [ "Oxidant-regulation of gene expression in the chronically inflamed intestine. \nIt is becoming increasingly apparent that the chronic gut inflammation observed in the idiopathic inflammatory bowel diseases (e.g. ulcerative colitis, Crohn's disease) is associated with enhanced production of leukocyte-derived oxidants. Oxidants such as hydrogen peroxide are known to activate certain transcription factors such as nuclear transcription factor kappa beta. Nuclear transcription factor kB (NF-kappa B) is a ubiquitous transcription factor and pleiotropic regulator of numerous genes involved in the immune and inflammatory responses. This transcription factor is activated via the selective phosphorylation, ubiquination and degradation of its inhibitor protein I-kB thereby allowing translocation of NF-kappa B into the nucleus where it upregulates the transcription of a variety of adhesion molecules (e.g. ICAM-1, VCAM-1), cytokines (TNF, IL-1, IL-6) and enzymes (iNOS). The proteolytic degradation of the post-translationally modified I-kappa B is known to be mediated by the 26S proteasome complex. Based upon work from our laboratory, we propose that inhibition of NF-kappa B activation produces significant anti inflammatory activity which may be mediated by the inhibition of transcription of certain pro-inflammatory mediators and adhesion molecules. " ], "offsets": [ [ 0, 1356 ] ] } ]

[ { "id": "9095577_T1", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 905, 911 ] ], "normalized": [] }, { "id": "9095577_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 913, 919 ] ], "normalized": [] }, { "id": "9095577_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 944, 948 ] ], "normalized": [] }, { "id": "9095577_T4", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 963, 967 ] ], "normalized": [] }, { "id": "9095577_T5", "type": "Protein", "text": [ "26S proteasome" ], "offsets": [ [ 1076, 1090 ] ], "normalized": [] } ]

[ { "id": "9095577_E1", "type": "Regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 834, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_E5" } ] }, { "id": "9095577_E2", "type": "Regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 834, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_E6" } ] }, { "id": "9095577_E3", "type": "Regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 834, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_E7" } ] }, { "id": "9095577_E4", "type": "Regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 834, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_E8" } ] }, { "id": "9095577_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 850, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_T4" } ] }, { "id": "9095577_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 850, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_T3" } ] }, { "id": "9095577_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 850, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_T2" } ] }, { "id": "9095577_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 850, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9095577_T1" } ] } ]

[]

[]

[ { "id": "10194443__text", "type": "abstract", "text": [ "Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets transcription factor Fli-1. \nGlycoprotein (GP) IX is a subunit of the von Willebrand receptor, GPIb-V-IX, which mediates adhesion of platelets to the subendothelium of damaged blood vessels. Previous characterization of the GPIX promoter identified a functional Ets site that, when disrupted, reduced promoter activity. However, the Ets protein(s) that regulated GPIX promoter expression was unknown. In this study, transient cotransfection of several GPIX promoter/reporter constructs into 293T kidney fibroblasts with a Fli-1 expression vector shows that the oncogenic protein Fli-1 can transactivate the GPIX promoter when an intact GPIX Ets site is present. In addition, Fli-1 binding of the GPIX Ets site was identified in antibody supershift experiments in nuclear extracts derived from hematopoietic human erythroleukemia cells. Comparative studies showed that Fli-1 was also able to transactivate the GPIbalpha and, to a lesser extent, the GPIIb promoter. Immunoblot analysis identified Fli-1 protein in lysates derived from platelets. In addition, expression of Fli-1 was identified immunohistochemically in megakaryocytes derived from CD34(+) cells treated with the megakaryocyte differentiation and proliferation factor, thrombopoietin. These results suggest that Fli-1 is likely to regulate lineage-specific genes during megakaryocytopoiesis. " ], "offsets": [ [ 0, 1434 ] ] } ]

[ { "id": "10194443_T1", "type": "Protein", "text": [ "glycoprotein IX" ], "offsets": [ [ 33, 48 ] ], "normalized": [] }, { "id": "10194443_T2", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 100, 105 ] ], "normalized": [] }, { "id": "10194443_T3", "type": "Protein", "text": [ "Glycoprotein (GP) IX" ], "offsets": [ [ 108, 128 ] ], "normalized": [] }, { "id": "10194443_T4", "type": "Protein", "text": [ "GPIX" ], "offsets": [ [ 303, 307 ] ], "normalized": [] }, { "id": "10194443_T5", "type": "Protein", "text": [ "GPIX" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "10194443_T6", "type": "Protein", "text": [ "GPIX" ], "offsets": [ [ 531, 535 ] ], "normalized": [] }, { "id": "10194443_T7", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 601, 606 ] ], "normalized": [] }, { "id": "10194443_T8", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 658, 663 ] ], "normalized": [] }, { "id": "10194443_T9", "type": "Protein", "text": [ "GPIX" ], "offsets": [ [ 686, 690 ] ], "normalized": [] }, { "id": "10194443_T10", "type": "Protein", "text": [ "GPIX" ], "offsets": [ [ 715, 719 ] ], "normalized": [] }, { "id": "10194443_T11", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 754, 759 ] ], "normalized": [] }, { "id": "10194443_T12", "type": "Protein", "text": [ "GPIX" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "10194443_T13", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 947, 952 ] ], "normalized": [] }, { "id": "10194443_T14", "type": "Protein", "text": [ "GPIbalpha" ], "offsets": [ [ 988, 997 ] ], "normalized": [] }, { "id": "10194443_T15", "type": "Protein", "text": [ "GPIIb" ], "offsets": [ [ 1027, 1032 ] ], "normalized": [] }, { "id": "10194443_T16", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 1074, 1079 ] ], "normalized": [] }, { "id": "10194443_T17", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 1150, 1155 ] ], "normalized": [] }, { "id": "10194443_T18", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 1224, 1228 ] ], "normalized": [] }, { "id": "10194443_T19", "type": "Protein", "text": [ "thrombopoietin" ], "offsets": [ [ 1311, 1325 ] ], "normalized": [] }, { "id": "10194443_T20", "type": "Protein", "text": [ "Fli-1" ], "offsets": [ [ 1354, 1359 ] ], "normalized": [] }, { "id": "10194443_T22", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 308, 316 ] ], "normalized": [] }, { "id": "10194443_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 691, 699 ] ], "normalized": [] }, { "id": "10194443_T30", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1033, 1041 ] ], "normalized": [] } ]

[ { "id": "10194443_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T1" }, { "role": "Cause", "ref_id": "10194443_T2" } ] }, { "id": "10194443_E2", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 372, 379 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T4" }, { "role": "Site", "ref_id": "10194443_T22" } ] }, { "id": "10194443_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 432, 441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_E4" } ] }, { "id": "10194443_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 456, 466 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T5" } ] }, { "id": "10194443_E5", "type": "Positive_regulation", "trigger": { "text": [ "transactivate" ], "offsets": [ [ 668, 681 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T9" }, { "role": "Cause", "ref_id": "10194443_T8" }, { "role": "Site", "ref_id": "10194443_T27" } ] }, { "id": "10194443_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 760, 767 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T11" } ] }, { "id": "10194443_E7", "type": "Positive_regulation", "trigger": { "text": [ "transactivate" ], "offsets": [ [ 970, 983 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T14" }, { "role": "Cause", "ref_id": "10194443_T13" }, { "role": "Site", "ref_id": "10194443_T30" } ] }, { "id": "10194443_E8", "type": "Positive_regulation", "trigger": { "text": [ "transactivate" ], "offsets": [ [ 970, 983 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T15" }, { "role": "Cause", "ref_id": "10194443_T13" }, { "role": "Site", "ref_id": "10194443_T30" } ] }, { "id": "10194443_E9", "type": "Gene_expression", "trigger": { "text": [ "identified" ], "offsets": [ [ 1063, 1073 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T16" } ] }, { "id": "10194443_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1136, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10194443_T17" } ] } ]

[]

[]

[ { "id": "8699118__text", "type": "abstract", "text": [ "Constitutive expression of specific interferon isotypes in peripheral blood leukocytes from normal individuals and in promonocytic U937 cells. \nConstitutive expression of IFN-alpha5 and IFN-beta was detected in different lymphoid cells including peripheral blood mononuclear cells from normal individuals following amplification of IFN mRNA by reverse transcriptase-polymerase chain reaction and direct sequencing of the amplified product. The activated form of the interferon-induced transcription factor complex ISGF3 was also detected in nuclear extracts from uninduced cells. Culture supernatants from uninduced U937 cells were also found to activate an ISRE cloned upstream of the luciferase reporter gene, indicating the presence of endogenous IFN activity equivalent to approximately 0.3 to 0.5 IU/mL. This endogenous IFN was also shown to play a role in maintaining the basal level of expression of the major histocompatibility class I genes in lymphoid cells. These results suggest that IFN-alpha5 and IFN-beta are produced at low levels in normal tissues and play an important role in the regulation of cell function and in the maintenance of homeostasis. " ], "offsets": [ [ 0, 1166 ] ] } ]

[ { "id": "8699118_T1", "type": "Protein", "text": [ "IFN-alpha5" ], "offsets": [ [ 171, 181 ] ], "normalized": [] }, { "id": "8699118_T2", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 186, 194 ] ], "normalized": [] }, { "id": "8699118_T3", "type": "Protein", "text": [ "IFN-alpha5" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "8699118_T4", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 1011, 1019 ] ], "normalized": [] } ]

[ { "id": "8699118_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 157, 167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8699118_T1" } ] }, { "id": "8699118_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 157, 167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8699118_T2" } ] }, { "id": "8699118_E3", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 1024, 1032 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8699118_T4" } ] }, { "id": "8699118_E4", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 1024, 1032 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8699118_T3" } ] } ]

[]

[]

[ { "id": "7969146__text", "type": "abstract", "text": [ "Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor promoter and binds PEBP2/CBF (AML1). \nThe receptor for the macrophage colony-stimulating factor (or colony-stimulating factor 1 [CSF-1]) is expressed from different promoters in monocytic cells and placental trophoblasts. We have demonstrated that the monocyte-specific expression of the CSF-1 receptor is regulated at the level of transcription by a tissue-specific promoter whose activity is stimulated by the monocyte/B-cell-specific transcription factor PU.1 (D.-E.Zhang, C.J.Hetherington, H.-M.Chen, and D.G.Tenen, Mol.Cell. Biol.14:373-381, 1994). Here we report that the tissue specificity of this promoter is also mediated by sequences in a region II (bp -88 to - 59), which lies 10 bp upstream from the PU.1-binding site. When analyzed by DNase footprinting, region II was protected preferentially in monocytic cells. Electrophoretic mobility shift assays confirmed that region II interacts specifically with nuclear proteins from monocytic cells. Two gel shift complexes (Mono A and Mono B) were formed with separate sequence elements within this region. Competition and supershift experiments indicate that Mono B contains a member of the polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) family, which includes the AML1 gene product, while Mono A is a distinct complex preferentially expressed in monocytic cells. Promoter constructs with mutations in these sequence elements were no longer expressed specifically in monocytes. Furthermore, multimerized region II sequence elements enhanced the activity of a heterologous thymidine kinase promoter in monocytic cells but not other cell types tested. These results indicate that the monocyte/B-cell-specific transcription factor PU.1 and the Mono A and Mono B protein complexes act in concert to regulate monocyte-specific transcription of the CSF-1 receptor. " ], "offsets": [ [ 0, 1990 ] ] } ]

[ { "id": "7969146_T1", "type": "Protein", "text": [ "colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor" ], "offsets": [ [ 71, 146 ] ], "normalized": [] }, { "id": "7969146_T2", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 177, 181 ] ], "normalized": [] }, { "id": "7969146_T3", "type": "Protein", "text": [ "macrophage colony-stimulating factor" ], "offsets": [ [ 206, 242 ] ], "normalized": [] }, { "id": "7969146_T4", "type": "Protein", "text": [ "colony-stimulating factor 1" ], "offsets": [ [ 247, 274 ] ], "normalized": [] }, { "id": "7969146_T5", "type": "Protein", "text": [ "CSF-1" ], "offsets": [ [ 276, 281 ] ], "normalized": [] }, { "id": "7969146_T6", "type": "Protein", "text": [ "CSF-1 receptor" ], "offsets": [ [ 435, 449 ] ], "normalized": [] }, { "id": "7969146_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 605, 609 ] ], "normalized": [] }, { "id": "7969146_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 859, 863 ] ], "normalized": [] }, { "id": "7969146_T9", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 1396, 1400 ] ], "normalized": [] }, { "id": "7969146_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1859, 1863 ] ], "normalized": [] }, { "id": "7969146_T11", "type": "Protein", "text": [ "CSF-1 receptor" ], "offsets": [ [ 1974, 1988 ] ], "normalized": [] }, { "id": "7969146_T13", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 147, 155 ] ], "normalized": [] } ]

[ { "id": "7969146_E1", "type": "Regulation", "trigger": { "text": [ "directs" ], "offsets": [ [ 33, 40 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_T1" }, { "role": "Site", "ref_id": "7969146_T13" } ] }, { "id": "7969146_E2", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 160, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_T2" } ] }, { "id": "7969146_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 417, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_T6" } ] }, { "id": "7969146_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 453, 462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_E3" } ] }, { "id": "7969146_E5", "type": "Binding", "trigger": { "text": [ "contains" ], "offsets": [ [ 1272, 1280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_T9" } ] }, { "id": "7969146_E6", "type": "Regulation", "trigger": { "text": [ "in concert to regulate" ], "offsets": [ [ 1912, 1934 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_E7" }, { "role": "Cause", "ref_id": "7969146_T10" } ] }, { "id": "7969146_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1953, 1966 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7969146_T11" } ] } ]

[]

[]

[ { "id": "8754855__text", "type": "abstract", "text": [ "Precise alignment of sites required for mu enhancer activation in B cells. \nThe lymphocyte-specific immunoglobulin mu heavy-chain gene intronic enhancer is regulated by multiple nuclear factors. The previously defined minimal enhancer containing the muA, muE3, and muB sites is transactivated by a combination of the ETS-domain proteins PU.1 and Ets-1 in nonlymphoid cells. The core GGAAs of the muA and muB sites are separated by 30 nucleotides, suggesting that ETS proteins bind to these sites from these same side of the DNA helix. We tested the necessity for appropriate spatial alignment of these elements by using mutated enhancers with altered spacings. A 4- or 10-bp insertion between muE3 and muB inactivated the mu enhancer in S194 plasma cells but did not affect in vitro binding of Ets-1, PU.1, or the muE3-binding protein TFE3, alone or in pairwise combinations. Circular permutation and phasing analyses demonstrated that PU.1 binding but not TFE3 or Ets-1 bends mu enhancer DNA toward the major groove. We propose that the requirement for precise spacing of the muA and muB elements is due in part to a directed DNA bend induced by PU.1. " ], "offsets": [ [ 0, 1153 ] ] } ]

[ { "id": "8754855_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 337, 341 ] ], "normalized": [] }, { "id": "8754855_T2", "type": "Protein", "text": [ "Ets-1" ], "offsets": [ [ 346, 351 ] ], "normalized": [] }, { "id": "8754855_T3", "type": "Protein", "text": [ "Ets-1" ], "offsets": [ [ 794, 799 ] ], "normalized": [] }, { "id": "8754855_T4", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 801, 805 ] ], "normalized": [] }, { "id": "8754855_T5", "type": "Protein", "text": [ "TFE3" ], "offsets": [ [ 835, 839 ] ], "normalized": [] }, { "id": "8754855_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 936, 940 ] ], "normalized": [] }, { "id": "8754855_T7", "type": "Protein", "text": [ "TFE3" ], "offsets": [ [ 957, 961 ] ], "normalized": [] }, { "id": "8754855_T8", "type": "Protein", "text": [ "Ets-1" ], "offsets": [ [ 965, 970 ] ], "normalized": [] }, { "id": "8754855_T9", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1147, 1151 ] ], "normalized": [] } ]

[ { "id": "8754855_E1", "type": "Binding", "trigger": { "text": [ "combination" ], "offsets": [ [ 298, 309 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T1" }, { "role": "Theme", "ref_id": "8754855_T2" } ] }, { "id": "8754855_E2", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 767, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_E6" } ] }, { "id": "8754855_E3", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 767, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_E5" } ] }, { "id": "8754855_E4", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 767, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_E7" } ] }, { "id": "8754855_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 783, 790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T5" } ] }, { "id": "8754855_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 783, 790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T3" } ] }, { "id": "8754855_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 783, 790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T4" } ] }, { "id": "8754855_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 941, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T8" } ] }, { "id": "8754855_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 941, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T7" } ] }, { "id": "8754855_E10", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 941, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8754855_T6" } ] } ]

[]

[]

[ { "id": "9199464__text", "type": "abstract", "text": [ "Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB. \nEhrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of human ehrlichiosis in the United States. Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of interleukin-1beta (IL-1beta), IL-8, and IL-10 genes in vitro but not the expression of tumor necrosis factor alpha (TNF-alpha) and IL-6 mRNAs. In this study, the effect of anti-E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory cytokines in human monocytes was examined. Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h, and the levels of cytokine mRNAs were evaluated by competitive reverse transcription-PCR. Anti-E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced mRNA expression of IL-1beta in THP-1 cells. The expression of TNF-alpha and IL-6 mRNAs was also induced. The levels of secreted IL-1beta, TNF-alpha, and IL-6 during 24 h of stimulation were comparable to those induced by Escherichia coli lipopolysaccharide at 1 microg/ml. Fab fragment of anti-E. chaffeensis immunoglobulin G complexed with E. chaffeensis did not induce any of these three cytokines, indicating that ehrlichial binding is required for IL-1beta mRNA expression and that binding of the immune complex to the Fc gamma receptor is required for TNF-alpha and IL-6 mRNA expression and enhanced IL-1beta mRNA expression. Furthermore, prolonged degradation of IkappaB-alpha and activation of NF-kappaB were demonstrated in THP-1 cells exposed to anti-E. chaffeensis serum and E. chaffeensis. This result implies that development of anti-E. chaffeensis antibody in patients can result in the production of major proinflammatory cytokines, which may play an important role in the pathophysiology of ehrlichiosis and immune responses to it. " ], "offsets": [ [ 0, 2172 ] ] } ]

[ { "id": "9199464_T1", "type": "Protein", "text": [ "IkappaB-alpha" ], "offsets": [ [ 172, 185 ] ], "normalized": [] }, { "id": "9199464_T2", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 498, 515 ] ], "normalized": [] }, { "id": "9199464_T3", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 517, 525 ] ], "normalized": [] }, { "id": "9199464_T4", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 528, 532 ] ], "normalized": [] }, { "id": "9199464_T5", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 538, 543 ] ], "normalized": [] }, { "id": "9199464_T6", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 585, 612 ] ], "normalized": [] }, { "id": "9199464_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 614, 623 ] ], "normalized": [] }, { "id": "9199464_T8", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 629, 633 ] ], "normalized": [] }, { "id": "9199464_T9", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1144, 1152 ] ], "normalized": [] }, { "id": "9199464_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1187, 1196 ] ], "normalized": [] }, { "id": "9199464_T11", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1201, 1205 ] ], "normalized": [] }, { "id": "9199464_T12", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1253, 1261 ] ], "normalized": [] }, { "id": "9199464_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1263, 1272 ] ], "normalized": [] }, { "id": "9199464_T14", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1278, 1282 ] ], "normalized": [] }, { "id": "9199464_T15", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1577, 1585 ] ], "normalized": [] }, { "id": "9199464_T16", "type": "Protein", "text": [ "Fc gamma receptor" ], "offsets": [ [ 1648, 1665 ] ], "normalized": [] }, { "id": "9199464_T17", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1682, 1691 ] ], "normalized": [] }, { "id": "9199464_T18", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1696, 1700 ] ], "normalized": [] }, { "id": "9199464_T19", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1730, 1738 ] ], "normalized": [] }, { "id": "9199464_T20", "type": "Protein", "text": [ "IkappaB-alpha" ], "offsets": [ [ 1794, 1807 ] ], "normalized": [] } ]

[ { "id": "9199464_E1", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 159, 168 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T1" } ] }, { "id": "9199464_E2", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E9" } ] }, { "id": "9199464_E3", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E10" } ] }, { "id": "9199464_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E7" } ] }, { "id": "9199464_E5", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E8" } ] }, { "id": "9199464_E6", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E11" } ] }, { "id": "9199464_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T3" } ] }, { "id": "9199464_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T4" } ] }, { "id": "9199464_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T5" } ] }, { "id": "9199464_E10", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 571, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T8" } ] }, { "id": "9199464_E11", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 571, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T7" } ] }, { "id": "9199464_E12", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1116, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E13" } ] }, { "id": "9199464_E13", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1125, 1140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T9" } ] }, { "id": "9199464_E14", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1173, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T10" } ] }, { "id": "9199464_E15", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1173, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T11" } ] }, { "id": "9199464_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1221, 1228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E14" } ] }, { "id": "9199464_E17", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1489, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T12" } ] }, { "id": "9199464_E18", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1489, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T14" } ] }, { "id": "9199464_E19", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1489, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T13" } ] }, { "id": "9199464_E20", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1564, 1572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E21" } ] }, { "id": "9199464_E21", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1591, 1601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T15" } ] }, { "id": "9199464_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1611, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T16" } ] }, { "id": "9199464_E23", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1669, 1677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E26" }, { "role": "Cause", "ref_id": "9199464_E22" } ] }, { "id": "9199464_E24", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1669, 1677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E25" }, { "role": "Cause", "ref_id": "9199464_E22" } ] }, { "id": "9199464_E25", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1706, 1716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T17" } ] }, { "id": "9199464_E26", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1706, 1716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T18" } ] }, { "id": "9199464_E27", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1721, 1729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E28" }, { "role": "Cause", "ref_id": "9199464_E22" } ] }, { "id": "9199464_E28", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1744, 1754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T19" } ] }, { "id": "9199464_E29", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1779, 1790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_T20" } ] }, { "id": "9199464_E30", "type": "Positive_regulation", "trigger": { "text": [ "demonstrated" ], "offsets": [ [ 1841, 1853 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9199464_E29" } ] } ]

[ { "id": "9199464_1", "entity_ids": [ "9199464_T2", "9199464_T3" ] }, { "id": "9199464_2", "entity_ids": [ "9199464_T6", "9199464_T7" ] } ]

[]

[ { "id": "2192264__text", "type": "abstract", "text": [ "Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1. \nExpression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 (IL-1)-responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat. This inhibitor did not affect protein kinase C-mediated gene transcription, suggesting that cyclic AMP-dependent protein kinases are involved in the signal transduction pathway for IL-1 in a number of responsive cell types. " ], "offsets": [ [ 0, 614 ] ] } ]

[ { "id": "2192264_T1", "type": "Protein", "text": [ "interleukin-1" ], "offsets": [ [ 91, 104 ] ], "normalized": [] }, { "id": "2192264_T2", "type": "Protein", "text": [ "interleukin-1" ], "offsets": [ [ 201, 214 ] ], "normalized": [] }, { "id": "2192264_T3", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 216, 220 ] ], "normalized": [] }, { "id": "2192264_T4", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 247, 251 ] ], "normalized": [] }, { "id": "2192264_T5", "type": "Protein", "text": [ "kappa immunoglobulin" ], "offsets": [ [ 302, 322 ] ], "normalized": [] }, { "id": "2192264_T6", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 571, 575 ] ], "normalized": [] } ]

[]

[ { "id": "2192264_1", "entity_ids": [ "2192264_T2", "2192264_T3" ] } ]

[]

[ { "id": "9031085__text", "type": "abstract", "text": [ "Expression of erythroid-specific genes in megakaryoblastic disorders. \nCurrently available data indicate that erythroid and megakaryocytic differentiation pathways are closely related to each other, and there may exist progenitor cells common to those two lineages may exist. Acute megakaryoblastic leukemia (AML-M7) and transient myeloproliferative disorder in Down's syndrome (TMD) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers. These blast cells express lineage-specific transcription factors such as GATA-1 common to these lineages and frequently express erythroid-specific mRNAs such as gamma-globin and erythroid delta-aminolevulinate synthase (ALAS-E), indicating that most of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes. These results suggest that blasts in M7 and TMD may correspond to progenitors of both erythroid and megakaryocytic lineages. " ], "offsets": [ [ 0, 935 ] ] } ]

[ { "id": "9031085_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 553, 559 ] ], "normalized": [] }, { "id": "9031085_T2", "type": "Protein", "text": [ "erythroid delta-aminolevulinate synthase" ], "offsets": [ [ 658, 698 ] ], "normalized": [] }, { "id": "9031085_T3", "type": "Protein", "text": [ "ALAS-E" ], "offsets": [ [ 700, 706 ] ], "normalized": [] } ]

[ { "id": "9031085_E1", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 498, 505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9031085_T1" } ] }, { "id": "9031085_E2", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 600, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9031085_T3" } ] } ]

[ { "id": "9031085_1", "entity_ids": [ "9031085_T2", "9031085_T3" ] } ]

[]

[ { "id": "9764907__text", "type": "abstract", "text": [ "Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells. \nCepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo. As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines. Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound. HIV-1 replication was determined by p24 antigen level. The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined. Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation. These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Since biscoclaurine alkaloids, containing cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients. " ], "offsets": [ [ 0, 1822 ] ] } ]

[ { "id": "9764907_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 488, 515 ] ], "normalized": [] }, { "id": "9764907_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 517, 526 ] ], "normalized": [] }, { "id": "9764907_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 739, 748 ] ], "normalized": [] }, { "id": "9764907_T4", "type": "Protein", "text": [ "p24 antigen" ], "offsets": [ [ 864, 875 ] ], "normalized": [] }, { "id": "9764907_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1113, 1122 ] ], "normalized": [] } ]

[]

[ { "id": "9764907_1", "entity_ids": [ "9764907_T1", "9764907_T2" ] } ]

[]

[ { "id": "9311921__text", "type": "abstract", "text": [ "NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily. \nActivation of the nuclear factor of activated T cells transcription factor (NF-AT) is a key event underlying lymphocyte action. The CAML (calcium-modulator and cyclophilin ligand) protein is a coinducer of NF-AT activation when overexpressed in Jurkat T cells. A member of the tumor necrosis factor receptor superfamily was isolated by virtue of its affinity for CAML. Cross-linking of this lymphocyte-specific protein, designated TACI (transmembrane activator and CAML-interactor), on the surface of transfected Jurkat cells with TACI-specific antibodies led to activation of the transcription factors NF-AT, AP-1, and NFkappaB. TACI-induced activation of NF-AT was specifically blocked by a dominant-negative CAML mutant, thus implicating CAML as a signaling intermediate. " ], "offsets": [ [ 0, 881 ] ] } ]

[ { "id": "9311921_T1", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 30, 34 ] ], "normalized": [] }, { "id": "9311921_T2", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 238, 242 ] ], "normalized": [] }, { "id": "9311921_T3", "type": "Protein", "text": [ "calcium-modulator and cyclophilin ligand" ], "offsets": [ [ 244, 284 ] ], "normalized": [] }, { "id": "9311921_T4", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 469, 473 ] ], "normalized": [] }, { "id": "9311921_T5", "type": "Protein", "text": [ "TACI" ], "offsets": [ [ 537, 541 ] ], "normalized": [] }, { "id": "9311921_T6", "type": "Protein", "text": [ "transmembrane activator and CAML-interactor" ], "offsets": [ [ 543, 586 ] ], "normalized": [] }, { "id": "9311921_T7", "type": "Protein", "text": [ "TACI" ], "offsets": [ [ 637, 641 ] ], "normalized": [] }, { "id": "9311921_T8", "type": "Protein", "text": [ "TACI" ], "offsets": [ [ 736, 740 ] ], "normalized": [] }, { "id": "9311921_T9", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 817, 821 ] ], "normalized": [] }, { "id": "9311921_T10", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 847, 851 ] ], "normalized": [] } ]

[ { "id": "9311921_E1", "type": "Gene_expression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 334, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9311921_T2" } ] }, { "id": "9311921_E2", "type": "Positive_regulation", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 334, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9311921_E1" } ] }, { "id": "9311921_E3", "type": "Binding", "trigger": { "text": [ "affinity" ], "offsets": [ [ 456, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9311921_T4" } ] } ]

[ { "id": "9311921_1", "entity_ids": [ "9311921_T2", "9311921_T3" ] }, { "id": "9311921_2", "entity_ids": [ "9311921_T5", "9311921_T6" ] } ]

[]

[ { "id": "9438495__text", "type": "abstract", "text": [ "Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation. \nTumor necrosis factor (TNF)-alpha controls T-cell activation and is a major inducer of human immunodeficiency virus (HIV)-1 replication in chronically infected cells. Therefore, we have investigated its role in primary cultures of HIV-infected human T lymphocytes by using neutralizing anti-TNF-alpha antibodies or TNF-alpha. Primary resting T lymphocytes produced TNF-alpha and supported HIV replication after T-cell receptor activation. Addition of neutralizing anti-TNF-alpha antibodies drastically reduced p24 antigen release and prevented CD4+ cell depletion associated with infection. Anti-TNF-alpha also prevented nuclear factor-kappa B (NF-kappa B) activation, and a good correlation between this inhibition and inhibition of HIV replication was observed. Moreover, supplementing the cultures with high doses of IL-2 reverted anti-TNF-alpha inhibition of cell proliferation but did not affect the inhibition of HIV p24 antigen release or NF-kappa B activation in the same cultures. Moreover, anti-TNF-alpha inhibited HIV-1 long terminal repeat (LTR)-driven transcription of a reporter gene in primary T cells in response to activation, either in the presence or the absence of HIV-1 Tat. Our results support an important role for autocrine TNF-alpha secretion in controlling HIV replication in primary T cells because of its ability to maintain NF-kappa B elevated in the nucleus of T cells. " ], "offsets": [ [ 0, 1595 ] ] } ]

[ { "id": "9438495_T1", "type": "Protein", "text": [ "Tumor necrosis factor (TNF)-alpha" ], "offsets": [ [ 195, 228 ] ], "normalized": [] }, { "id": "9438495_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 486, 495 ] ], "normalized": [] }, { "id": "9438495_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 510, 519 ] ], "normalized": [] }, { "id": "9438495_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 560, 569 ] ], "normalized": [] }, { "id": "9438495_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 664, 673 ] ], "normalized": [] }, { "id": "9438495_T6", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 705, 708 ] ], "normalized": [] }, { "id": "9438495_T7", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 739, 742 ] ], "normalized": [] }, { "id": "9438495_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 791, 800 ] ], "normalized": [] }, { "id": "9438495_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "9438495_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1034, 1043 ] ], "normalized": [] }, { "id": "9438495_T11", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 1118, 1121 ] ], "normalized": [] }, { "id": "9438495_T12", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1200, 1209 ] ], "normalized": [] }, { "id": "9438495_T13", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1386, 1389 ] ], "normalized": [] }, { "id": "9438495_T14", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1443, 1452 ] ], "normalized": [] } ]

[ { "id": "9438495_E1", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 551, 559 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_T4" } ] }, { "id": "9438495_E2", "type": "Negative_regulation", "trigger": { "text": [ "neutralizing" ], "offsets": [ [ 646, 658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_T5" } ] }, { "id": "9438495_E3", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 697, 704 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_E4" } ] }, { "id": "9438495_E4", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 717, 724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_T6" } ] }, { "id": "9438495_E5", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1089, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_E6" }, { "role": "Cause", "ref_id": "9438495_T9" } ] }, { "id": "9438495_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1100, 1110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_E7" } ] }, { "id": "9438495_E7", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 1130, 1137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_T11" } ] }, { "id": "9438495_E8", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1453, 1462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9438495_T14" } ] } ]

[]

[]

[ { "id": "8139041__text", "type": "abstract", "text": [ "A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1. \nAnalysis of the chromatin organization of the integrated human immunodeficiency virus type 1 (HIV-1) genome has previously revealed a major constitutive DNase I-hypersensitive site associated with the pol gene (E. Verdin, J. Virol. 65:6790-6799, 1991). In the present report, high-resolution mapping of this site with DNase I and micrococcal nuclease identified a nucleosome-free region centered around nucleotides (nt) 4490 to 4766. A 500-bp fragment encompassing this hypersensitive site (nt 4481 to 4982) exhibited transcription-enhancing activity (two- to threefold) when it was cloned in its natural position with respect to the HIV-1 promoter after transient transfection in U937 and CEM cells. Using in vitro footprinting and gel shift assays, we have identified four distinct binding sites for nuclear proteins within this positive regulatory element. Site B (nt 4519 to 4545) specifically bound four distinct nuclear protein complexes: a ubiquitous factor, a T-cell-specific factor, a B-cell-specific factor, and the monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1. In most HIV-1 isolates in which this PU box was not conserved, it was replaced by a binding site for the related factor Ets1. Factors binding to site C (nt 4681 to 4701) had a DNA-binding specificity similar to that of factors binding to site B, except for PU.1/Spi-1. A GC box containing a binding site for Sp1 was identified (nt 4623 to 4631). Site D (nt 4816 to 4851) specifically bound a ubiquitously expressed factor. These results identify a transcriptional regulatory element associated with a nuclease-hypersensitive site in the pol gene of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis-regulatory elements. " ], "offsets": [ [ 0, 1898 ] ] } ]

[ { "id": "8139041_T1", "type": "Protein", "text": [ "pol" ], "offsets": [ [ 94, 97 ] ], "normalized": [] }, { "id": "8139041_T2", "type": "Protein", "text": [ "pol" ], "offsets": [ [ 345, 348 ] ], "normalized": [] }, { "id": "8139041_T3", "type": "Protein", "text": [ "DNase I" ], "offsets": [ [ 462, 469 ] ], "normalized": [] }, { "id": "8139041_T4", "type": "Protein", "text": [ "micrococcal nuclease" ], "offsets": [ [ 474, 494 ] ], "normalized": [] }, { "id": "8139041_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1232, 1236 ] ], "normalized": [] }, { "id": "8139041_T6", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1237, 1242 ] ], "normalized": [] }, { "id": "8139041_T7", "type": "Protein", "text": [ "Ets1" ], "offsets": [ [ 1364, 1368 ] ], "normalized": [] }, { "id": "8139041_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1501, 1505 ] ], "normalized": [] }, { "id": "8139041_T9", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] }, { "id": "8139041_T10", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1552, 1555 ] ], "normalized": [] }, { "id": "8139041_T11", "type": "Protein", "text": [ "pol" ], "offsets": [ [ 1781, 1784 ] ], "normalized": [] } ]

[ { "id": "8139041_E1", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1042, 1047 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8139041_T5" } ] }, { "id": "8139041_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1328, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8139041_T7" } ] }, { "id": "8139041_E3", "type": "Binding", "trigger": { "text": [ "containing a binding site" ], "offsets": [ [ 1522, 1547 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8139041_T10" } ] } ]

[ { "id": "8139041_1", "entity_ids": [ "8139041_T8", "8139041_T9" ] }, { "id": "8139041_2", "entity_ids": [ "8139041_T5", "8139041_T6" ] } ]

[]

[ { "id": "7858491__text", "type": "abstract", "text": [ "Expression and genomic configuration of GM-CSF, IL-3, M-CSF receptor (C-FMS), early growth response gene-1 (EGR-1) and M-CSF genes in primary myelodysplastic syndromes. \nPeripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes (MDS) in advanced stage were enriched for blasts and tested for (1) karyotype, (2) genomic configuration and (3) expression of IL-3, GM-CSF, FMS and EGR-1 genes which are all located on the long arm of chromosome 5. The expression of the M-CSF gene, that has been recently reassigned to the short arm of chromosome 1 (lp), was also investigated. Aims of the study were to (1) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and (2) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells. The latter issue was investigated by comparing, in 8 cases, constitutive DNA from skin fibroblasts with leukemic DNA. Eleven of the 17 patients had abnormal karyotypes. The M-CSF gene was expressed in 6 cases and the FMS and the EGR-1 genes were expressed in 2 of the latter cases. An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the M-CSF and FMS genes. No germline changes or rearrangements were observed in any of the genes studied. Thus, deregulation of genes encoding for certain hemopoietic growth factors or receptors does not seem to represent a major mechanism of MDS progression. " ], "offsets": [ [ 0, 1567 ] ] } ]

[ { "id": "7858491_T1", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 40, 46 ] ], "normalized": [] }, { "id": "7858491_T2", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 48, 52 ] ], "normalized": [] }, { "id": "7858491_T3", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 54, 68 ] ], "normalized": [] }, { "id": "7858491_T4", "type": "Protein", "text": [ "C-FMS" ], "offsets": [ [ 70, 75 ] ], "normalized": [] }, { "id": "7858491_T5", "type": "Protein", "text": [ "early growth response gene-1" ], "offsets": [ [ 78, 106 ] ], "normalized": [] }, { "id": "7858491_T6", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 108, 113 ] ], "normalized": [] }, { "id": "7858491_T7", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 119, 124 ] ], "normalized": [] }, { "id": "7858491_T8", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "7858491_T9", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 401, 407 ] ], "normalized": [] }, { "id": "7858491_T10", "type": "Protein", "text": [ "FMS" ], "offsets": [ [ 409, 412 ] ], "normalized": [] }, { "id": "7858491_T11", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 417, 422 ] ], "normalized": [] }, { "id": "7858491_T12", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 506, 511 ] ], "normalized": [] }, { "id": "7858491_T13", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1092, 1097 ] ], "normalized": [] }, { "id": "7858491_T14", "type": "Protein", "text": [ "FMS" ], "offsets": [ [ 1136, 1139 ] ], "normalized": [] }, { "id": "7858491_T15", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1148, 1153 ] ], "normalized": [] }, { "id": "7858491_T16", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1311, 1316 ] ], "normalized": [] }, { "id": "7858491_T17", "type": "Protein", "text": [ "FMS" ], "offsets": [ [ 1321, 1324 ] ], "normalized": [] } ]

[ { "id": "7858491_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T2" } ] }, { "id": "7858491_E2", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T4" } ] }, { "id": "7858491_E3", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T6" } ] }, { "id": "7858491_E4", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T1" } ] }, { "id": "7858491_E5", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T7" } ] }, { "id": "7858491_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 381, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T10" } ] }, { "id": "7858491_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 381, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T11" } ] }, { "id": "7858491_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 381, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T9" } ] }, { "id": "7858491_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 381, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T8" } ] }, { "id": "7858491_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 488, 498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T12" } ] }, { "id": "7858491_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 677, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T11" } ] }, { "id": "7858491_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 677, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T12" } ] }, { "id": "7858491_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 677, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T10" } ] }, { "id": "7858491_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 677, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T8" } ] }, { "id": "7858491_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 677, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T9" } ] }, { "id": "7858491_E16", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1107, 1116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T13" } ] }, { "id": "7858491_E17", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1165, 1174 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T15" } ] }, { "id": "7858491_E18", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1165, 1174 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T14" } ] }, { "id": "7858491_E19", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1292, 1301 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T16" } ] }, { "id": "7858491_E20", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1292, 1301 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T17" } ] }, { "id": "7858491_E21", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 1344, 1351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T9" } ] }, { "id": "7858491_E22", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 1344, 1351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T12" } ] }, { "id": "7858491_E23", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 1344, 1351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T11" } ] }, { "id": "7858491_E24", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 1344, 1351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T10" } ] }, { "id": "7858491_E25", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 1344, 1351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7858491_T8" } ] } ]

[ { "id": "7858491_1", "entity_ids": [ "7858491_T3", "7858491_T4" ] }, { "id": "7858491_2", "entity_ids": [ "7858491_T5", "7858491_T6" ] } ]

[]

[ { "id": "2123468__text", "type": "abstract", "text": [ "Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. \nStimulation of T lymphocytes through their antigen receptor leads to the appearance of several transcription factors, including NF-AT and NF-kappa B, which are involved in regulating genes required for immunologic activation. To investigate the activity of a single transcription factor in individual viable cells, we have applied an assay that uses the fluorescence-activated cell sorter to quantitate beta-galactosidase (beta-gal). We have analyzed the distribution of NF-AT transcriptional activity among T cells undergoing activation by using a construct in which three tandem copies of the NF-AT-binding site directs transcription of the lacZ gene. Unexpectedly, stimulation of cloned stably transfected Jurkat T cells leads to a bimodal pattern of beta-gal expression in which some cells express no beta-gal and others express high levels. This expression pattern cannot be accounted for by cell-cycle position or heritable variation. Further results, in which beta-gal activity is correlated with NF-AT-binding activity, indicate that the concentration of NF-AT must exceed a critical threshold before transcription initiates. This threshold likely reflects the NF-AT concentration-dependent assembly of transcription complexes at the promoter. Similar constructs controlled by NF-kappa B or the entire interleukin-2 enhancer show bimodal expression patterns during induction, suggesting that thresholds set by the concentration of transcription factors may be a common property of inducible genes. " ], "offsets": [ [ 0, 1653 ] ] } ]

[ { "id": "2123468_T1", "type": "Protein", "text": [ "beta-galactosidase" ], "offsets": [ [ 550, 568 ] ], "normalized": [] }, { "id": "2123468_T2", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 570, 578 ] ], "normalized": [] }, { "id": "2123468_T3", "type": "Protein", "text": [ "lacZ" ], "offsets": [ [ 790, 794 ] ], "normalized": [] }, { "id": "2123468_T4", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 901, 909 ] ], "normalized": [] }, { "id": "2123468_T5", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 952, 960 ] ], "normalized": [] }, { "id": "2123468_T6", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 1114, 1122 ] ], "normalized": [] }, { "id": "2123468_T7", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1457, 1470 ] ], "normalized": [] } ]

[ { "id": "2123468_E1", "type": "Regulation", "trigger": { "text": [ "directs" ], "offsets": [ [ 761, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E2" } ] }, { "id": "2123468_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 769, 782 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_T3" } ] }, { "id": "2123468_E3", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 871, 876 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E7" } ] }, { "id": "2123468_E4", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 871, 876 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E6" } ] }, { "id": "2123468_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 910, 920 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_T4" } ] }, { "id": "2123468_E6", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 941, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_T5" } ] }, { "id": "2123468_E7", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 972, 979 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_T5" } ] }, { "id": "2123468_E8", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 980, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E7" } ] }, { "id": "2123468_E9", "type": "Regulation", "trigger": { "text": [ "accounted" ], "offsets": [ [ 1027, 1036 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E5" } ] }, { "id": "2123468_E10", "type": "Regulation", "trigger": { "text": [ "show" ], "offsets": [ [ 1480, 1484 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E11" } ] }, { "id": "2123468_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1493, 1503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_T7" } ] }, { "id": "2123468_E12", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1520, 1529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2123468_E11" } ] } ]

[ { "id": "2123468_1", "entity_ids": [ "2123468_T1", "2123468_T2" ] } ]

[]

[ { "id": "9919536__text", "type": "abstract", "text": [ "Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome. \nIt is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response. Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B. Indeed, the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease. " ], "offsets": [ [ 0, 603 ] ] } ]

[]

[]

[]

[]

[ { "id": "1493333__text", "type": "abstract", "text": [ "I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding. \nThe active nuclear form of the NF-kappa B transcription factor complex is composed of two DNA binding subunits, NF-kappa B p65 and NF-kappa B p50, both of which share extensive N-terminal sequence homology with the v-rel oncogene product. The NF-kappa B p65 subunit provides the transactivation activity in this complex and serves as an intracellular receptor for a cytoplasmic inhibitor of NF-kappa B, termed I kappa B. In contrast, NF-kappa B p50 alone fails to stimulate kappa B-directed transcription, and based on prior in vitro studies, is not directly regulated by I kappa B. To investigate the molecular basis for the critical regulatory interaction between NF-kappa B and I kappa B/MAD-3, a series of human NF-kappa B p65 mutants was identified that functionally segregated DNA binding, I kappa B-mediated inhibition, and I kappa B-induced nuclear exclusion of this transcription factor. Results from in vivo expression studies performed with these NF-kappa B p65 mutants revealed the following: 1) I kappa B/MAD-3 completely inhibits NF-kappa B p65-dependent transcriptional activation mediated through the human immunodeficiency virus type 1 kappa B enhancer in human T lymphocytes, 2) the binding of I kappa B/MAD-3 to NF-kappa B p65 is sufficient to retarget NF-kappa B p65 from the nucleus to the cytoplasm, 3) selective deletion of the functional nuclear localization signal present in the Rel homology domain of NF-kappa B p65 disrupts its ability to engage I kappa B/MAD-3, and 4) the unique C-terminus of NF-kappa B p65 attenuates its own nuclear localization and contains sequences that are required for I kappa B-mediated inhibition of NF-kappa B p65 DNA binding activity. Together, these findings suggest that the nuclear localization signal and transactivation domain of NF-kappa B p65 constitute a bipartite system that is critically involved in the inhibitory function of I kappa B/MAD-3. Unexpectedly, our in vivo studies also demonstrate that I kappa B/MAD-3 binds directly to NF-kappa B p50. This interaction is functional as it leads to retargeting of NF-kappa B p50 from the nucleus to the cytoplasm. However, no loss of DNA binding activity is observed, presumably reflecting the unique C-terminal domain that is distinct from that present in NF-kappa B p65. " ], "offsets": [ [ 0, 2441 ] ] } ]

[ { "id": "1493333_T1", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 10, 15 ] ], "normalized": [] }, { "id": "1493333_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 68, 71 ] ], "normalized": [] }, { "id": "1493333_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 134, 137 ] ], "normalized": [] }, { "id": "1493333_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 275, 278 ] ], "normalized": [] }, { "id": "1493333_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 294, 297 ] ], "normalized": [] }, { "id": "1493333_T6", "type": "Protein", "text": [ "v-rel" ], "offsets": [ [ 367, 372 ] ], "normalized": [] }, { "id": "1493333_T7", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 406, 409 ] ], "normalized": [] }, { "id": "1493333_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 597, 600 ] ], "normalized": [] }, { "id": "1493333_T9", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 843, 848 ] ], "normalized": [] }, { "id": "1493333_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "1493333_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1121, 1124 ] ], "normalized": [] }, { "id": "1493333_T12", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1170, 1175 ] ], "normalized": [] }, { "id": "1493333_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1207, 1210 ] ], "normalized": [] }, { "id": "1493333_T14", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1374, 1379 ] ], "normalized": [] }, { "id": "1493333_T15", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1394, 1397 ] ], "normalized": [] }, { "id": "1493333_T16", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1435, 1438 ] ], "normalized": [] }, { "id": "1493333_T17", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1591, 1594 ] ], "normalized": [] }, { "id": "1493333_T18", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1636, 1641 ] ], "normalized": [] }, { "id": "1493333_T19", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1686, 1689 ] ], "normalized": [] }, { "id": "1493333_T20", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1819, 1822 ] ], "normalized": [] }, { "id": "1493333_T21", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1956, 1959 ] ], "normalized": [] }, { "id": "1493333_T22", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 2058, 2063 ] ], "normalized": [] }, { "id": "1493333_T23", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 2131, 2136 ] ], "normalized": [] }, { "id": "1493333_T24", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 2166, 2169 ] ], "normalized": [] }, { "id": "1493333_T25", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 2243, 2246 ] ], "normalized": [] }, { "id": "1493333_T26", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 2436, 2439 ] ], "normalized": [] }, { "id": "1493333_T28", "type": "Entity", "text": [ "nuclear localization signal" ], "offsets": [ [ 26, 53 ] ], "normalized": [] }, { "id": "1493333_T38", "type": "Entity", "text": [ "cytoplasm" ], "offsets": [ [ 1463, 1472 ] ], "normalized": [] }, { "id": "1493333_T40", "type": "Entity", "text": [ "nuclear localization signal" ], "offsets": [ [ 1514, 1541 ] ], "normalized": [] }, { "id": "1493333_T43", "type": "Entity", "text": [ "C-terminus" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "1493333_T45", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1709, 1716 ] ], "normalized": [] }, { "id": "1493333_T53", "type": "Entity", "text": [ "cytoplasm" ], "offsets": [ [ 2271, 2280 ] ], "normalized": [] } ]

[ { "id": "1493333_E1", "type": "Negative_regulation", "trigger": { "text": [ "masks" ], "offsets": [ [ 16, 21 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T2" }, { "role": "Cause", "ref_id": "1493333_T1" }, { "role": "Site", "ref_id": "1493333_T28" } ] }, { "id": "1493333_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 115, 122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E3" }, { "role": "Cause", "ref_id": "1493333_T1" } ] }, { "id": "1493333_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 142, 149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T3" } ] }, { "id": "1493333_E4", "type": "Binding", "trigger": { "text": [ "complex" ], "offsets": [ [ 215, 222 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T4" }, { "role": "Theme", "ref_id": "1493333_T5" } ] }, { "id": "1493333_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 246, 253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T5" } ] }, { "id": "1493333_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 246, 253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T4" } ] }, { "id": "1493333_E7", "type": "Binding", "trigger": { "text": [ "receptor" ], "offsets": [ [ 503, 511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T7" } ] }, { "id": "1493333_E8", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 711, 720 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T8" } ] }, { "id": "1493333_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1353, 1360 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T14" }, { "role": "Theme", "ref_id": "1493333_T15" } ] }, { "id": "1493333_E10", "type": "Positive_regulation", "trigger": { "text": [ "sufficient" ], "offsets": [ [ 1401, 1411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E11" }, { "role": "Cause", "ref_id": "1493333_E9" } ] }, { "id": "1493333_E11", "type": "Localization", "trigger": { "text": [ "retarget" ], "offsets": [ [ 1415, 1423 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T16" }, { "role": "ToLoc", "ref_id": "1493333_T38" } ] }, { "id": "1493333_E12", "type": "Negative_regulation", "trigger": { "text": [ "deletion" ], "offsets": [ [ 1487, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T17" }, { "role": "Site", "ref_id": "1493333_T40" } ] }, { "id": "1493333_E13", "type": "Negative_regulation", "trigger": { "text": [ "disrupts" ], "offsets": [ [ 1595, 1603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E14" }, { "role": "Cause", "ref_id": "1493333_E12" } ] }, { "id": "1493333_E14", "type": "Binding", "trigger": { "text": [ "engage" ], "offsets": [ [ 1619, 1625 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T17" }, { "role": "Theme", "ref_id": "1493333_T18" } ] }, { "id": "1493333_E15", "type": "Negative_regulation", "trigger": { "text": [ "attenuates" ], "offsets": [ [ 1690, 1700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E16" }, { "role": "Cause", "ref_id": "1493333_T19" }, { "role": "CSite", "ref_id": "1493333_T43" } ] }, { "id": "1493333_E16", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1717, 1729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T19" }, { "role": "ToLoc", "ref_id": "1493333_T45" } ] }, { "id": "1493333_E17", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1762, 1770 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E18" }, { "role": "Cause", "ref_id": "1493333_T19" }, { "role": "CSite", "ref_id": "1493333_T43" } ] }, { "id": "1493333_E18", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1794, 1804 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E19" } ] }, { "id": "1493333_E19", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1827, 1834 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T20" } ] }, { "id": "1493333_E20", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 2137, 2142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T23" }, { "role": "Theme", "ref_id": "1493333_T24" } ] }, { "id": "1493333_E21", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 2208, 2213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_E22" }, { "role": "Cause", "ref_id": "1493333_E20" } ] }, { "id": "1493333_E22", "type": "Localization", "trigger": { "text": [ "retargeting" ], "offsets": [ [ 2217, 2228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1493333_T25" }, { "role": "ToLoc", "ref_id": "1493333_T53" } ] } ]

[]

[]

[ { "id": "7520093__text", "type": "abstract", "text": [ "Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers. \nAn ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the survival of infected B cells through upregulation of the bcl-2 oncogene was first suggested by experiments involving gene transfection and the selection of stable LMP1+ clones (S.Henderson, M. Rowe, C.Gregory, F.Wang, E.Kieff, and A.Rickinson, Cell 65:1107-1115, 1991). However, it was not possible to ascertain whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an artifact of the selection procedure whereby rare Bcl-2+ cells already present in the starting population might best be able to tolerate the potentially toxic effects of LMP1. We therefore reexamined this issue by using two different experimental approaches that allowed LMP1- induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures; activation of the NF-kappa B transcription factor and upregulation of the cell adhesion molecule ICAM-1 were used as early indices of LMP1 function. In the first approach, stable clones of two B-cell lines carrying an LMP1 gene under the control of an inducible metallothionein promoter were induced to express LMP1 in all cells. Activation of NK-kappa B and upregulation of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of Bcl-2. In the second approach, we tested the generality of this phenomenon by transiently expressing LMP1 from a strong constitutively active promoter in a range of different cell types. All six B-cell lines tested showed NF-kappa B activation in response to LMP1 expression, and this was followed in five of six lines by expression of ICAM-1 and Bcl-2. In the same experiments, all three non-B-cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any effect upon Bcl-2. We therefore conclude that Bcl-2 upregulation is part of the panoply of cellular changes induced by LMP1 but that the effect is cell type specific. Our data also suggest that whilst NF-kappa B may be an essential component of LMP1 signal transduction, other cell-specific factors may be required to effect some functions of the viral protein. " ], "offsets": [ [ 0, 2364 ] ] } ]

[ { "id": "7520093_T1", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "7520093_T2", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 72, 76 ] ], "normalized": [] }, { "id": "7520093_T3", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 259, 263 ] ], "normalized": [] }, { "id": "7520093_T4", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 336, 341 ] ], "normalized": [] }, { "id": "7520093_T5", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "7520093_T6", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "7520093_T7", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 648, 652 ] ], "normalized": [] }, { "id": "7520093_T8", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 719, 724 ] ], "normalized": [] }, { "id": "7520093_T9", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 839, 843 ] ], "normalized": [] }, { "id": "7520093_T10", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "7520093_T11", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1172, 1178 ] ], "normalized": [] }, { "id": "7520093_T12", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1209, 1213 ] ], "normalized": [] }, { "id": "7520093_T13", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "7520093_T14", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1386, 1390 ] ], "normalized": [] }, { "id": "7520093_T15", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1450, 1456 ] ], "normalized": [] }, { "id": "7520093_T16", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1529, 1534 ] ], "normalized": [] }, { "id": "7520093_T17", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1630, 1634 ] ], "normalized": [] }, { "id": "7520093_T18", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1788, 1792 ] ], "normalized": [] }, { "id": "7520093_T19", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1865, 1871 ] ], "normalized": [] }, { "id": "7520093_T20", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1876, 1881 ] ], "normalized": [] }, { "id": "7520093_T21", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1968, 1974 ] ], "normalized": [] }, { "id": "7520093_T22", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 2014, 2019 ] ], "normalized": [] }, { "id": "7520093_T23", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 2048, 2053 ] ], "normalized": [] }, { "id": "7520093_T24", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 2121, 2125 ] ], "normalized": [] }, { "id": "7520093_T25", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 2247, 2251 ] ], "normalized": [] } ]

[ { "id": "7520093_E1", "type": "Positive_regulation", "trigger": { "text": [ "Upregulation" ], "offsets": [ [ 0, 12 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T1" }, { "role": "Cause", "ref_id": "7520093_T2" } ] }, { "id": "7520093_E2", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 316, 328 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T4" }, { "role": "Cause", "ref_id": "7520093_T3" } ] }, { "id": "7520093_E3", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 605, 617 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T6" }, { "role": "Cause", "ref_id": "7520093_E4" } ] }, { "id": "7520093_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 653, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T7" } ] }, { "id": "7520093_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 946, 953 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T9" }, { "role": "Cause", "ref_id": "7520093_T10" } ] }, { "id": "7520093_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1000, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T10" } ] }, { "id": "7520093_E7", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1129, 1141 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T11" } ] }, { "id": "7520093_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1367, 1374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_E9" } ] }, { "id": "7520093_E9", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1378, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T14" } ] }, { "id": "7520093_E10", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1434, 1446 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T15" } ] }, { "id": "7520093_E11", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1513, 1525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T16" } ] }, { "id": "7520093_E12", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1619, 1629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T17" } ] }, { "id": "7520093_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1793, 1803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T18" } ] }, { "id": "7520093_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1851, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T20" } ] }, { "id": "7520093_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1851, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T19" } ] }, { "id": "7520093_E16", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1975, 1987 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T21" }, { "role": "Cause", "ref_id": "7520093_E13" } ] }, { "id": "7520093_E17", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 2002, 2008 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T22" }, { "role": "Cause", "ref_id": "7520093_E13" } ] }, { "id": "7520093_E18", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 2054, 2066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7520093_T23" } ] } ]

[]

[]

[ { "id": "7925300__text", "type": "abstract", "text": [ "Activation of NF-kappa B in vivo is regulated by multiple phosphorylations. \nThe activation of nuclear factor kappa B (NF-kappa B) in intact cells is mechanistically not well understood. Therefore we investigated the modifications imposed on NF-kappa B/I kappa B components following stimulation and show that the final step of NF-kappa B induction in vivo involves phosphorylation of several members of the NF-kappa B/I kappa B protein families. In HeLa cells as well as in B cells, TNF-alpha rapidly induced nuclear translocation primarily of p50-p65, but not of c-rel. Both NF-kappa B precursors and I kappa B alpha became strongly phosphorylated with the same kinetics. In addition to the inducible phosphorylation after stimulation, B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha. Phosphorylation was accompanied by induced processing of the precursors p100 and p105 and by degradation of I kappa B alpha. As an in vitro model we show that phosphorylation of p105 impedes its ability to interact with NF-kappa B, as has been shown before for I kappa B alpha. Surprisingly, even p65, but not c-rel, was phosphorylated after induction in vivo, suggesting that TNF-alpha selectively activates only specific NF-kappa B heteromers and that modifications regulate not only I kappa B molecules but also NF-kappa B molecules. In fact, cellular NF-kappa B activity was phosphorylation-dependent and the DNA binding activity of p65-containing NF-kappa B was enhanced by phosphorylation in vitro. Furthermore, we found that the induction by hydrogen peroxide of NF-kappa B translocation to the nucleus, which is assumed to be triggered by reactive oxygen intermediates, also coincided with incorporation of phosphate into the same subunits that were modified after stimulation by TNF-alpha. Thus, phosphorylation appears to be a general mechanism for activation of NF-kappa B in vivo. " ], "offsets": [ [ 0, 1952 ] ] } ]

[ { "id": "7925300_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 484, 493 ] ], "normalized": [] }, { "id": "7925300_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "7925300_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 549, 552 ] ], "normalized": [] }, { "id": "7925300_T4", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 565, 570 ] ], "normalized": [] }, { "id": "7925300_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 603, 618 ] ], "normalized": [] }, { "id": "7925300_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 834, 837 ] ], "normalized": [] }, { "id": "7925300_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 842, 857 ] ], "normalized": [] }, { "id": "7925300_T8", "type": "Protein", "text": [ "p100" ], "offsets": [ [ 931, 935 ] ], "normalized": [] }, { "id": "7925300_T9", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "7925300_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 967, 982 ] ], "normalized": [] }, { "id": "7925300_T11", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "7925300_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1120, 1135 ] ], "normalized": [] }, { "id": "7925300_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1156, 1159 ] ], "normalized": [] }, { "id": "7925300_T14", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "7925300_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1236, 1245 ] ], "normalized": [] }, { "id": "7925300_T16", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1496, 1499 ] ], "normalized": [] }, { "id": "7925300_T17", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1847, 1856 ] ], "normalized": [] }, { "id": "7925300_T19", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 510, 517 ] ], "normalized": [] } ]

[ { "id": "7925300_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 502, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_E4" }, { "role": "Cause", "ref_id": "7925300_T1" } ] }, { "id": "7925300_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 502, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_E6" }, { "role": "Cause", "ref_id": "7925300_T1" } ] }, { "id": "7925300_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 502, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_E5" }, { "role": "Cause", "ref_id": "7925300_T1" } ] }, { "id": "7925300_E4", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 518, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T2" }, { "role": "ToLoc", "ref_id": "7925300_T19" } ] }, { "id": "7925300_E5", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 518, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T4" }, { "role": "ToLoc", "ref_id": "7925300_T19" } ] }, { "id": "7925300_E6", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 518, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T3" }, { "role": "ToLoc", "ref_id": "7925300_T19" } ] }, { "id": "7925300_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 635, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T5" } ] }, { "id": "7925300_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 819, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T7" } ] }, { "id": "7925300_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 819, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T6" } ] }, { "id": "7925300_E10", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 952, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T10" } ] }, { "id": "7925300_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1018, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T12" } ] }, { "id": "7925300_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1018, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T11" } ] }, { "id": "7925300_E13", "type": "Negative_regulation", "trigger": { "text": [ "impedes" ], "offsets": [ [ 1042, 1049 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_E16" }, { "role": "Cause", "ref_id": "7925300_E12" } ] }, { "id": "7925300_E14", "type": "Negative_regulation", "trigger": { "text": [ "impedes" ], "offsets": [ [ 1042, 1049 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_E15" }, { "role": "Cause", "ref_id": "7925300_E11" } ] }, { "id": "7925300_E15", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1065, 1073 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T12" } ] }, { "id": "7925300_E16", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1065, 1073 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T11" } ] }, { "id": "7925300_E17", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1180, 1194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T13" } ] }, { "id": "7925300_E18", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1180, 1194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T14" } ] }, { "id": "7925300_E19", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1201, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T14" } ] }, { "id": "7925300_E20", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1201, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T13" } ] }, { "id": "7925300_E21", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1476, 1492 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_T16" } ] }, { "id": "7925300_E22", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1526, 1534 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7925300_E21" } ] } ]

[]

[]

[ { "id": "10357820__text", "type": "abstract", "text": [ "Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes. \nHere we show that the lymphoid lineage-determining factors Ikaros and Aiolos can function as strong transcriptional repressors. This function is mediated through two repression domains and is dependent upon the promoter context and cell type. Repression by Ikaros proteins correlates with hypo-acetylation of core histones at promoter sites and is relieved by histone deacetylase inhibitors. Consistent with these findings, Ikaros and its repression domains can interact in vivo and in vitro with the mSin3 family of co-repressors which bind to histone deacetylases. Based on these and our recent findings of associations between Ikaros and Mi-2-HDAC, we propose that Ikaros family members modulate gene expression during lymphocyte development by recruiting distinct histone deacetylase complexes to specific promoters. " ], "offsets": [ [ 0, 905 ] ] } ]

[ { "id": "10357820_T1", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "10357820_T2", "type": "Protein", "text": [ "Aiolos" ], "offsets": [ [ 25, 31 ] ], "normalized": [] }, { "id": "10357820_T3", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 143, 149 ] ], "normalized": [] }, { "id": "10357820_T4", "type": "Protein", "text": [ "Aiolos" ], "offsets": [ [ 154, 160 ] ], "normalized": [] }, { "id": "10357820_T5", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 341, 347 ] ], "normalized": [] }, { "id": "10357820_T6", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 508, 514 ] ], "normalized": [] }, { "id": "10357820_T7", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 714, 720 ] ], "normalized": [] }, { "id": "10357820_T8", "type": "Protein", "text": [ "Mi-2-HDAC" ], "offsets": [ [ 725, 734 ] ], "normalized": [] }, { "id": "10357820_T9", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 752, 758 ] ], "normalized": [] } ]

[ { "id": "10357820_E1", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 546, 554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10357820_T6" } ] }, { "id": "10357820_E2", "type": "Binding", "trigger": { "text": [ "associations" ], "offsets": [ [ 693, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10357820_T7" }, { "role": "Theme", "ref_id": "10357820_T8" } ] } ]

[]

[]

[ { "id": "10101034__text", "type": "abstract", "text": [ "Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid. \nThe therapeutic potential of drugs that block the induction of cyclooxygenase-2 has been emphasized. When two 4-trifluoromethyl salicylate derivatives [2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB)] were compared with aspirin and sodium salicylate as cyclooxygenase-2 (COX-2) inhibitors, we observed that in bacterial lipopolysaccharide-activated human blood, triflusal, aspirin, and HTB, but not sodium salicylate, inhibited COX-2-mediated prostaglandin E2 (PGE2) production (IC50 = 0.16, 0.18, 0.39, and >10 mM, respectively). However, only triflusal and aspirin inhibited purified COX-2 enzyme. To test this apparent discrepancy, we realized that HTB and triflusal (but neither aspirin nor salicylate) produced a concentration-dependent inhibition of COX-2 protein expression in peripheral human mononuclear cells. This observation was further confirmed in a rat air pouch model in vivo, in which both aspirin and triflusal inhibited PGE2 production (ID50 = 18.9 and 11.4 mg/kg p.o., respectively) but only triflusal-treated animals showed a decrease in COX-2 expression. This different behavior may be, at least in part, due to the ability of HTB and triflusal to block the activation of the transcription factor nuclear factor-kappaB to a higher extent than aspirin and sodium salicylate. Thus, in addition to inhibiting the COX-2 activity at therapeutic concentrations, triflusal is able to block through its metabolite HTB the expression of new enzyme, and hence the resumption of PGE2 synthesis. Triflusal and HTB may exert beneficial effects in processes in which de novo COX-2 expression is involved and, in a broader sense, in pathological situations in which genes under nuclear factor-kappaB control are up-regulated. " ], "offsets": [ [ 0, 1992 ] ] } ]

[ { "id": "10101034_T1", "type": "Protein", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 14, 30 ] ], "normalized": [] }, { "id": "10101034_T2", "type": "Protein", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 239, 255 ] ], "normalized": [] }, { "id": "10101034_T3", "type": "Protein", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 512, 528 ] ], "normalized": [] }, { "id": "10101034_T4", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 530, 535 ] ], "normalized": [] }, { "id": "10101034_T5", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 687, 692 ] ], "normalized": [] }, { "id": "10101034_T6", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 845, 850 ] ], "normalized": [] }, { "id": "10101034_T7", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1015, 1020 ] ], "normalized": [] }, { "id": "10101034_T8", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1318, 1323 ] ], "normalized": [] }, { "id": "10101034_T9", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1591, 1596 ] ], "normalized": [] }, { "id": "10101034_T10", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1842, 1847 ] ], "normalized": [] } ]

[ { "id": "10101034_E1", "type": "Negative_regulation", "trigger": { "text": [ "Inhibition" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_E2" } ] }, { "id": "10101034_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 31, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_T1" } ] }, { "id": "10101034_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 826, 835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_T6" } ] }, { "id": "10101034_E4", "type": "Positive_regulation", "trigger": { "text": [ "produced" ], "offsets": [ [ 966, 974 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_E5" } ] }, { "id": "10101034_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1001, 1011 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_E6" } ] }, { "id": "10101034_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1029, 1039 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_T7" } ] }, { "id": "10101034_E7", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1306, 1314 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_E8" } ] }, { "id": "10101034_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1324, 1334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_T8" } ] }, { "id": "10101034_E9", "type": "Negative_regulation", "trigger": { "text": [ "block" ], "offsets": [ [ 1658, 1663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_E10" } ] }, { "id": "10101034_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1695, 1705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_T8" } ] }, { "id": "10101034_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1848, 1858 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10101034_T10" } ] } ]

[ { "id": "10101034_1", "entity_ids": [ "10101034_T3", "10101034_T4" ] } ]

[]

[ { "id": "10497131__text", "type": "abstract", "text": [ "Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A [see comments] \nThe flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs. " ], "offsets": [ [ 0, 1028 ] ] } ]

[]

[]

[]

[]

[ { "id": "9306134__text", "type": "abstract", "text": [ "Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water. \n1. In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce programmed cell death. 2. Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene-contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3. Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4. When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 +/- 1.8 and 12.1 +/- 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals (P < 0.0001, Mann-Whitney U-Test). MTBE and benzene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumulated at the S-G2/M boundaries. 5. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kappa B). NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death. " ], "offsets": [ [ 0, 2057 ] ] } ]

[]

[]

[]

[]

[ { "id": "10352258__text", "type": "abstract", "text": [ "In vivo inhibition of NF-kappa B in T-lineage cells leads to a dramatic decrease in cell proliferation and cytokine production and to increased cell apoptosis in response to mitogenic stimuli, but not to abnormal thymopoiesis. \nTo understand the role of NF-kappa B complexes in T cell development and activation, we have generated transgenic mice in which RelA and c-Rel complexes were selectively inhibited in the T-lineage cells by specific expression of a trans-dominant form of I kappa B alpha. Transgene expression did not affect the thymic development, but led to lowered numbers of splenic T cells and to a dramatic decrease in the ex vivo proliferative response of splenic T lymphocytes. Analysis of IL-2 and IL-2R alpha expression demonstrated that the perturbation of the proliferation response was not attributable to an abnormal expression of these genes. In contrast, expression of IL-4, IL-10, and IFN-gamma was strongly inhibited in the transgenic T cells. The proliferative deficiency of the transgenic T cells was associated with an increased apoptosis. These results point out the involvement of NF-kappa B/Rel family proteins in growth signaling pathways by either regulating proteins involved in the IL-2 signaling or by functionally interfering with the cell cycle progression. " ], "offsets": [ [ 0, 1299 ] ] } ]

[ { "id": "10352258_T1", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 356, 360 ] ], "normalized": [] }, { "id": "10352258_T2", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 365, 370 ] ], "normalized": [] }, { "id": "10352258_T3", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 482, 497 ] ], "normalized": [] }, { "id": "10352258_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "10352258_T5", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 717, 728 ] ], "normalized": [] }, { "id": "10352258_T6", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 895, 899 ] ], "normalized": [] }, { "id": "10352258_T7", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 901, 906 ] ], "normalized": [] }, { "id": "10352258_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 912, 921 ] ], "normalized": [] }, { "id": "10352258_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1220, 1224 ] ], "normalized": [] } ]

[ { "id": "10352258_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 398, 407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T1" }, { "role": "Cause", "ref_id": "10352258_E3" } ] }, { "id": "10352258_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 398, 407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T2" }, { "role": "Cause", "ref_id": "10352258_E3" } ] }, { "id": "10352258_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 443, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T3" } ] }, { "id": "10352258_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 509, 519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T3" } ] }, { "id": "10352258_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 729, 739 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T5" } ] }, { "id": "10352258_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 729, 739 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T4" } ] }, { "id": "10352258_E7", "type": "Negative_regulation", "trigger": { "text": [ "abnormal" ], "offsets": [ [ 832, 840 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_E9" } ] }, { "id": "10352258_E8", "type": "Negative_regulation", "trigger": { "text": [ "abnormal" ], "offsets": [ [ 832, 840 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_E10" } ] }, { "id": "10352258_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 841, 851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T4" } ] }, { "id": "10352258_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 841, 851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T5" } ] }, { "id": "10352258_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 881, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T7" } ] }, { "id": "10352258_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 881, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T6" } ] }, { "id": "10352258_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 881, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_T8" } ] }, { "id": "10352258_E14", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 935, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_E12" } ] }, { "id": "10352258_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 935, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10352258_E11" } ] } ]

[]

[]

[ { "id": "8383677__text", "type": "abstract", "text": [ "Stimulation of interleukin-1 alpha and interleukin-1 beta production in human monocytes by protein phosphatase 1 and 2A inhibitors. \nProtein phosphatases 1 and 2A are important in regulating cellular functions by controlling the phosphorylation state of their substrates. In human monocytes, the inhibitors of these phosphatases, okadaic acid and calyculin A, were found to increase the mRNA accumulation and cytokine production of interleukin-1 beta and interleukin-1 alpha. The increased mRNA accumulation was found to be primarily because of the increase in the transcription rate of the interleukin-1 genes. Stimulation of interleukin-1 gene transcription may be caused by the stimulation of transcription factor activities, including those of AP-1, by these protein phosphatase inhibitors. Okadaic acid increased the synthesis of the interleukin-1 beta precursor and mature forms and their secretion. This increased processing and secretion correlated with the stimulation of IL-1 beta convertase mRNA accumulation. The stimulation of interleukin-1 alpha production by okadaic acid was more modest than that of interleukin-1 beta. However, the phosphorylation of the precursor interleukin-1 alpha cytokine was increased. These results show that protein phosphatase 1 and 2A inhibitors exert multiple effects on cytokine production in human monocytes and suggest that these two phosphatases play important roles in regulating interleukin-1 production. " ], "offsets": [ [ 0, 1456 ] ] } ]

[ { "id": "8383677_T1", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 15, 34 ] ], "normalized": [] }, { "id": "8383677_T2", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 39, 57 ] ], "normalized": [] }, { "id": "8383677_T3", "type": "Protein", "text": [ "protein phosphatase 1" ], "offsets": [ [ 91, 112 ] ], "normalized": [] }, { "id": "8383677_T4", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 117, 119 ] ], "normalized": [] }, { "id": "8383677_T5", "type": "Protein", "text": [ "Protein phosphatases 1" ], "offsets": [ [ 133, 155 ] ], "normalized": [] }, { "id": "8383677_T6", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 160, 162 ] ], "normalized": [] }, { "id": "8383677_T7", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 432, 450 ] ], "normalized": [] }, { "id": "8383677_T8", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 455, 474 ] ], "normalized": [] }, { "id": "8383677_T9", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 748, 752 ] ], "normalized": [] }, { "id": "8383677_T10", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 839, 857 ] ], "normalized": [] }, { "id": "8383677_T11", "type": "Protein", "text": [ "IL-1 beta convertase" ], "offsets": [ [ 981, 1001 ] ], "normalized": [] }, { "id": "8383677_T12", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 1040, 1059 ] ], "normalized": [] }, { "id": "8383677_T13", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 1116, 1134 ] ], "normalized": [] }, { "id": "8383677_T14", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 1182, 1201 ] ], "normalized": [] }, { "id": "8383677_T15", "type": "Protein", "text": [ "protein phosphatase 1" ], "offsets": [ [ 1250, 1271 ] ], "normalized": [] }, { "id": "8383677_T16", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 1276, 1278 ] ], "normalized": [] } ]

[ { "id": "8383677_E1", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E5" }, { "role": "Cause", "ref_id": "8383677_T4" } ] }, { "id": "8383677_E2", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E6" }, { "role": "Cause", "ref_id": "8383677_T3" } ] }, { "id": "8383677_E3", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E5" }, { "role": "Cause", "ref_id": "8383677_T3" } ] }, { "id": "8383677_E4", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E6" }, { "role": "Cause", "ref_id": "8383677_T4" } ] }, { "id": "8383677_E5", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 58, 68 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T2" } ] }, { "id": "8383677_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 58, 68 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T1" } ] }, { "id": "8383677_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 120, 130 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T4" } ] }, { "id": "8383677_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 120, 130 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T3" } ] }, { "id": "8383677_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 296, 306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T6" } ] }, { "id": "8383677_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 296, 306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T5" } ] }, { "id": "8383677_E11", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E15" } ] }, { "id": "8383677_E12", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E16" } ] }, { "id": "8383677_E13", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E18" } ] }, { "id": "8383677_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E17" } ] }, { "id": "8383677_E15", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 387, 404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T8" } ] }, { "id": "8383677_E16", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 387, 404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T7" } ] }, { "id": "8383677_E17", "type": "Gene_expression", "trigger": { "text": [ "cytokine production" ], "offsets": [ [ 409, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T7" } ] }, { "id": "8383677_E18", "type": "Gene_expression", "trigger": { "text": [ "cytokine production" ], "offsets": [ [ 409, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T8" } ] }, { "id": "8383677_E19", "type": "Positive_regulation", "trigger": { "text": [ "because of" ], "offsets": [ [ 534, 544 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E12" } ] }, { "id": "8383677_E20", "type": "Positive_regulation", "trigger": { "text": [ "because of" ], "offsets": [ [ 534, 544 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E11" } ] }, { "id": "8383677_E21", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 681, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T9" } ] }, { "id": "8383677_E22", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 808, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E23" } ] }, { "id": "8383677_E23", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 895, 904 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T10" } ] }, { "id": "8383677_E24", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 966, 977 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E25" } ] }, { "id": "8383677_E25", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1007, 1019 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T11" } ] }, { "id": "8383677_E26", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1025, 1036 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E27" } ] }, { "id": "8383677_E27", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1060, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T12" } ] }, { "id": "8383677_E28", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1060, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T13" } ] }, { "id": "8383677_E29", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1149, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_T14" } ] }, { "id": "8383677_E30", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1215, 1224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8383677_E29" } ] } ]

[]

[]

[ { "id": "10446999__text", "type": "abstract", "text": [ "Induction of a functional vitamin D receptor in all-trans-retinoic acid-induced monocytic differentiation of M2-type leukemic blast cells. \nDifferent types of acute myeloid leukemia blast cells were induced to differentiate in vitro with all-trans-retinoic acid (ATRA) and vitamin D3 (VD). M0/M1 leukemic cells are not sensitive to differentiating agents, whereas M3 leukemic cells are induced to undergo granulocytic differentiation after ATRA treatment but are not sensitive to VD. M2 leukemic blast cells behave differently because they undergo monocytic differentiation with both the differentiation inducers. To gain some insight into the maturation of M2-type leukemic cells, we studied the molecular mechanisms underlying monocytic differentiation induced by ATRA and VD in spontaneous M2 blast cells as well as in Kasumi-1 cells (an acute myeloid leukemia M2-type cell line). Our results indicate that ATRA as well as VD efficiently increases the nuclear abundance of VD receptor (VDR) and promotes monocytic differentiation. VDR is functionally active in ATRA-treated Kasumi-1 cells because it efficiently heterodimerizes with retinoid X receptor, binds to a DR3-type vitamin D-responsive element, and activates the transcription of a vitamin D-responsive element-regulated reporter gene. Consistent with these findings, VD-responsive genes are induced by ATRA treatment of Kasumi-1 cells, suggesting that the genetic program underlying monocytic differentiation is activated. The molecular mechanism by which ATRA increases the nuclear abundance of a functional VDR is still unknown, but our data clearly indicate that the M2 leukemic cell context is only permissive of monocytic differentiation. " ], "offsets": [ [ 0, 1707 ] ] } ]

[ { "id": "10446999_T1", "type": "Protein", "text": [ "vitamin D receptor" ], "offsets": [ [ 26, 44 ] ], "normalized": [] }, { "id": "10446999_T2", "type": "Protein", "text": [ "VD receptor" ], "offsets": [ [ 976, 987 ] ], "normalized": [] }, { "id": "10446999_T3", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 989, 992 ] ], "normalized": [] }, { "id": "10446999_T4", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1034, 1037 ] ], "normalized": [] }, { "id": "10446999_T5", "type": "Protein", "text": [ "retinoid X receptor" ], "offsets": [ [ 1136, 1155 ] ], "normalized": [] }, { "id": "10446999_T6", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1572, 1575 ] ], "normalized": [] }, { "id": "10446999_T9", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 955, 962 ] ], "normalized": [] }, { "id": "10446999_T15", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1538, 1545 ] ], "normalized": [] } ]

[ { "id": "10446999_E1", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 0, 9 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_T1" } ] }, { "id": "10446999_E2", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 941, 950 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_E3" } ] }, { "id": "10446999_E3", "type": "Localization", "trigger": { "text": [ "abundance" ], "offsets": [ [ 963, 972 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_T3" }, { "role": "AtLoc", "ref_id": "10446999_T9" } ] }, { "id": "10446999_E4", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 1054, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_T4" } ] }, { "id": "10446999_E5", "type": "Binding", "trigger": { "text": [ "heterodimerizes" ], "offsets": [ [ 1115, 1130 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_T4" }, { "role": "Theme", "ref_id": "10446999_T5" } ] }, { "id": "10446999_E6", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1157, 1162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_T4" } ] }, { "id": "10446999_E7", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1524, 1533 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_E8" } ] }, { "id": "10446999_E8", "type": "Localization", "trigger": { "text": [ "abundance" ], "offsets": [ [ 1546, 1555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10446999_T6" }, { "role": "AtLoc", "ref_id": "10446999_T15" } ] } ]

[ { "id": "10446999_1", "entity_ids": [ "10446999_T2", "10446999_T3" ] } ]

[]

[ { "id": "8015552__text", "type": "abstract", "text": [ "Multiple prolactin-responsive elements mediate G1 and S phase expression of the interferon regulatory factor-1 gene. \nThe interferon regulatory factor-1 (IRF-1) gene is both an immediate-early G1 phase gene and an S phase gene inducible by PRL in rat Nb2 T lymphocytes. To understand the mechanism by which PRL regulates the biphasic expression of IRF-1, we cloned the rat IRF-1 gene and functionally characterized the IRF-1 promoter. Upon transfection into Nb2 T cells, 1.7 kilobases (kb) of IRF-1 5'-flanking DNA linked to a chloramphenicol acetyl transferase (CAT) reporter gene mediated a 30-fold induction of CAT enzyme activity in response to 24 h of PRL stimulation. Deletion mutants containing 1.3, 0.6, and 0.2 kb 5'-flanking DNA were incrementally less transcriptionally active, although 0.2 kb still mediated a 12-fold induction by PRL. The sequence between -1.7 and -0.2 kb linked to a heterologous thymidine kinase promoter failed to respond to PRL stimulation, suggesting that the activity of upstream PRL response elements may require an interaction with promoter-proximal elements. By assaying CAT enzyme activity across a 24-h PRL induction time course, we were able to assign G1 vs. S phase PRL responses of the IRF-1 gene to different regions of the IRF-1 5'-flanking and promoter DNA. The 0.2-kb IRF-CAT construct was induced by PRL stimulation during the G1 phase of the cell cycle. In contrast, the 1.7-kb IRF-CAT construct was inducible by PRL during both G1 and S phase of the cell cycle. Hence, the PRL-induced biphasic expression of the IRF-1 gene appears to be controlled by separate PRL-responsive elements: elements in the first 0.2 kb of the IRF-1 promoter region act during early activation, and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression. " ], "offsets": [ [ 0, 1834 ] ] } ]

[ { "id": "8015552_T1", "type": "Protein", "text": [ "prolactin" ], "offsets": [ [ 9, 18 ] ], "normalized": [] }, { "id": "8015552_T2", "type": "Protein", "text": [ "interferon regulatory factor-1" ], "offsets": [ [ 80, 110 ] ], "normalized": [] }, { "id": "8015552_T3", "type": "Protein", "text": [ "interferon regulatory factor-1" ], "offsets": [ [ 122, 152 ] ], "normalized": [] }, { "id": "8015552_T4", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 154, 159 ] ], "normalized": [] }, { "id": "8015552_T5", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 240, 243 ] ], "normalized": [] }, { "id": "8015552_T6", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 307, 310 ] ], "normalized": [] }, { "id": "8015552_T7", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "8015552_T8", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 373, 378 ] ], "normalized": [] }, { "id": "8015552_T9", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 419, 424 ] ], "normalized": [] }, { "id": "8015552_T10", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 493, 498 ] ], "normalized": [] }, { "id": "8015552_T11", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 527, 561 ] ], "normalized": [] }, { "id": "8015552_T12", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 563, 566 ] ], "normalized": [] }, { "id": "8015552_T13", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 614, 617 ] ], "normalized": [] }, { "id": "8015552_T14", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 657, 660 ] ], "normalized": [] }, { "id": "8015552_T15", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 843, 846 ] ], "normalized": [] }, { "id": "8015552_T16", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 958, 961 ] ], "normalized": [] }, { "id": "8015552_T17", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1016, 1019 ] ], "normalized": [] }, { "id": "8015552_T18", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1110, 1113 ] ], "normalized": [] }, { "id": "8015552_T19", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1144, 1147 ] ], "normalized": [] }, { "id": "8015552_T20", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1209, 1212 ] ], "normalized": [] }, { "id": "8015552_T21", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [] }, { "id": "8015552_T22", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1269, 1274 ] ], "normalized": [] }, { "id": "8015552_T23", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1349, 1352 ] ], "normalized": [] }, { "id": "8015552_T24", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] }, { "id": "8015552_T25", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1524, 1527 ] ], "normalized": [] }, { "id": "8015552_T26", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1563, 1568 ] ], "normalized": [] }, { "id": "8015552_T27", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1611, 1614 ] ], "normalized": [] }, { "id": "8015552_T28", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1672, 1677 ] ], "normalized": [] }, { "id": "8015552_T40", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 1678, 1693 ] ], "normalized": [] } ]

[ { "id": "8015552_E1", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 39, 46 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_E2" } ] }, { "id": "8015552_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 62, 72 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T2" } ] }, { "id": "8015552_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 227, 236 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T4" }, { "role": "Cause", "ref_id": "8015552_T5" } ] }, { "id": "8015552_E4", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 311, 320 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_E5" }, { "role": "Cause", "ref_id": "8015552_T6" } ] }, { "id": "8015552_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 334, 344 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T8" } ] }, { "id": "8015552_E6", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 582, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_E7" } ] }, { "id": "8015552_E7", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 601, 610 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T13" }, { "role": "Cause", "ref_id": "8015552_T14" } ] }, { "id": "8015552_E8", "type": "Regulation", "trigger": { "text": [ "responses" ], "offsets": [ [ 1213, 1222 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T21" }, { "role": "Cause", "ref_id": "8015552_T20" } ] }, { "id": "8015552_E9", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1528, 1535 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_E10" }, { "role": "Cause", "ref_id": "8015552_T25" } ] }, { "id": "8015552_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1545, 1555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T26" } ] }, { "id": "8015552_E11", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1588, 1598 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_E9" }, { "role": "Cause", "ref_id": "8015552_T28" }, { "role": "CSite", "ref_id": "8015552_T40" } ] }, { "id": "8015552_E12", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1588, 1598 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_E9" } ] }, { "id": "8015552_E13", "type": "Positive_regulation", "trigger": { "text": [ "act" ], "offsets": [ [ 1694, 1697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8015552_T28" }, { "role": "Site", "ref_id": "8015552_T40" } ] } ]

[ { "id": "8015552_1", "entity_ids": [ "8015552_T11", "8015552_T12" ] }, { "id": "8015552_2", "entity_ids": [ "8015552_T3", "8015552_T4" ] } ]

[]

[ { "id": "9032264__text", "type": "abstract", "text": [ "Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription factor. \nChicken NF-M transcription factor, in cooperation with either c-Myb or v-Myb, is active in the combinatorial activation of myeloid-cell-specific genes in heterologous cell types, such as embryonic fibroblasts. In humans, similar effects were observed with homologous members of the CCAAT/enhancer-binding protein (C/EBP) family of transcriptional regulators, especially the human homolog of chicken NF-M, C/EBP-beta (NF-IL6). However, the NF-IL6 gene is expressed in a variety of nonmyeloid cell types and is strongly inducible in response to inflammatory stimuli, making it an unlikely candidate to have an exclusive role as a combinatorial differentiation switch during myelopoiesis in human cells. By using a reverse transcription-PCR-based approach and a set of primers specific for the DNA-binding domains of highly homologous members of the C/EBP family of transcriptional regulators, we have cloned a novel human gene encoding a member of the C/EBP gene family, identified as the human homolog of CRP1, C/EBP-epsilon. A 1.2-kb cDNA encoding full-length human C/EBP-epsilon was cloned from a promyelocyte-late myeloblast-derived lambda gt11 library. Molecular analysis of the cDNA and genomic clones indicated the presence of two exons encoding a protein with an apparent molecular mass of 32 kDa and a pI of 9.5. Primer extension analysis of C/EBP-epsilon mRNA detected a single major transcription start site approximately 200 bp upstream of the start codon. The putative promoter area is similar to those of several other myeloid-cell-specific genes in that it contains no TATAAA box but has a number of purine-rich stretches with multiple sites for the factors of the Ets family of transcriptional regulators. Northern blot analyses indicated a highly restricted mRNA expression pattern, with the strongest expression occurring in promyelocyte and late-myeloblast-like cell lines. Western blot and immunoprecipitation studies using rabbit anti-C/EBP-epsilon antibodies raised against the N-terminal portion of C/EBP-epsilon (amino acids 1 to 115) showed that C/EBP-epsilon is a 32-kDa nuclear phosphoprotein. The human C/EBP-epsilon protein exhibited strong and specific binding to double-stranded DNA containing consensus C/EBP sites. Cotransfection of the C/EBP-epsilon sense and antisense expression constructs together with chloramphenicol acetyltransferase reporter vectors containing myeloid-cell-specific c-mim and human myeloperoxidase promoters suggested a role for C/EBP-epsilon transcription factor in the regulation of a subset of myeloid-cell-specific genes. Transient tranfection of a promyelocyte cell line (NB4) with a C/EBP-epsilon expression plasmid increased cell growth by sevenfold, while antisense C/EBP-epsilon caused a fivefold decrease in clonal growth of these cells. " ], "offsets": [ [ 0, 2890 ] ] } ]

[ { "id": "9032264_T1", "type": "Protein", "text": [ "NF-M" ], "offsets": [ [ 94, 98 ] ], "normalized": [] }, { "id": "9032264_T2", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 148, 153 ] ], "normalized": [] }, { "id": "9032264_T3", "type": "Protein", "text": [ "NF-M" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "9032264_T4", "type": "Protein", "text": [ "C/EBP-beta" ], "offsets": [ [ 491, 501 ] ], "normalized": [] }, { "id": "9032264_T5", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 503, 509 ] ], "normalized": [] }, { "id": "9032264_T6", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 525, 531 ] ], "normalized": [] }, { "id": "9032264_T7", "type": "Protein", "text": [ "CRP1" ], "offsets": [ [ 1090, 1094 ] ], "normalized": [] }, { "id": "9032264_T8", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 1096, 1109 ] ], "normalized": [] }, { "id": "9032264_T9", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 1152, 1165 ] ], "normalized": [] }, { "id": "9032264_T10", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 1435, 1448 ] ], "normalized": [] }, { "id": "9032264_T11", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2040, 2053 ] ], "normalized": [] }, { "id": "9032264_T12", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2106, 2119 ] ], "normalized": [] }, { "id": "9032264_T13", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2155, 2168 ] ], "normalized": [] }, { "id": "9032264_T14", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2215, 2228 ] ], "normalized": [] }, { "id": "9032264_T15", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2354, 2367 ] ], "normalized": [] }, { "id": "9032264_T16", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2571, 2584 ] ], "normalized": [] }, { "id": "9032264_T17", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2731, 2744 ] ], "normalized": [] }, { "id": "9032264_T18", "type": "Protein", "text": [ "C/EBP-epsilon" ], "offsets": [ [ 2816, 2829 ] ], "normalized": [] } ]

[ { "id": "9032264_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 540, 549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_T6" } ] }, { "id": "9032264_E2", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 604, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_E1" } ] }, { "id": "9032264_E3", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1864, 1874 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_T6" } ] }, { "id": "9032264_E4", "type": "Positive_regulation", "trigger": { "text": [ "strongest" ], "offsets": [ [ 1893, 1902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_E3" } ] }, { "id": "9032264_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 2267, 2274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_T14" } ] }, { "id": "9032264_E6", "type": "Gene_expression", "trigger": { "text": [ "tranfection" ], "offsets": [ [ 2678, 2689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_T17" } ] }, { "id": "9032264_E7", "type": "Positive_regulation", "trigger": { "text": [ "tranfection" ], "offsets": [ [ 2678, 2689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_E6" } ] }, { "id": "9032264_E8", "type": "Negative_regulation", "trigger": { "text": [ "antisense" ], "offsets": [ [ 2806, 2815 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_T18" } ] }, { "id": "9032264_E9", "type": "Gene_expression", "trigger": { "text": [ "antisense" ], "offsets": [ [ 2806, 2815 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9032264_T18" } ] } ]

[ { "id": "9032264_1", "entity_ids": [ "9032264_T3", "9032264_T4", "9032264_T5" ] }, { "id": "9032264_2", "entity_ids": [ "9032264_T7", "9032264_T8" ] } ]

[]

[ { "id": "1628621__text", "type": "abstract", "text": [ "Transcription factor AP-2 activates gene expression of HTLV-I. \nThe HTLV-I LTR contains three conserved regulatory elements known as 21 base pair repeats which are required for stimulation of gene expression by the transactivator protein tax. Mutagenesis indicates that the 21 bp repeats can be subdivided into three motifs, A, B and C, each of which influences the level of tax activation. The A site in the 21 bp repeat has strong homology with previously described binding sites for the transcription factor AP-2. We demonstrated that AP-2 mRNA was present in T-lymphocytes and that cellular factors from both non-transformed and transformed T-lymphocytes specifically bound to the consensus motif for AP-2 in each 21 bp. To determine the role of AP-2 in the regulation of the HTLV-I LTR gene expression, we used an AP-2 cDNA in DNA binding and transient expression assays. Gel retardation and methylation interference studies revealed that bacterially produced AP-2 bound specifically and with high affinity to all three 21 bp repeats, and that it required the core sequence AGGC for specific binding. Binding of AP-2 prevented the subsequent binding of members of the CREB/ATF family to an adjacent regulatory motif in the 21 bp repeat. Transfection of an AP-2 expression construct into T-lymphocytes activated gene expression from the HTLV-I LTR. At least two 21 bp repeats were required for high levels of AP-2 activation and mutagenesis of the AP-2 consensus binding sequences in the 21 bp repeats eliminate this activation. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1567 ] ] } ]

[ { "id": "1628621_T1", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 238, 241 ] ], "normalized": [] }, { "id": "1628621_T2", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 375, 378 ] ], "normalized": [] } ]

[ { "id": "1628621_E1", "type": "Regulation", "trigger": { "text": [ "influences the level" ], "offsets": [ [ 351, 371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1628621_E2" } ] }, { "id": "1628621_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 379, 389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1628621_T2" } ] } ]

[]

[]

[ { "id": "9122255__text", "type": "abstract", "text": [ "Neuronal (type I) nitric oxide synthase regulates nuclear factor kappaB activity and immunologic (type II) nitric oxide synthase expression. \nNitric oxide subserves diverse physiologic roles in the nervous system. NO is produced from at least three different NO synthase (NOS) isoforms: neuronal NOS (nNOS), endothelial NOS, and immunologic NOS (iNOS). We show that nNOS is the predominant isoform constitutively expressed in glia. NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB (NF kappaB) as NOS inhibitors enhance basal NF kappaB activation. Pyrrolidine dithiocarbamate (PDTC) is an inhibitor of NF kappaB in most cells; however, we show that PDTC is also a potent scavenger of NO through formation of mononitrosyl iron complexes with PDTC. In Jurkat cells, a human T-cell lymphoma cell line, tumor necrosis factor-alpha (TNF-alpha) induces NF kappaB activation that is inhibited by PDTC. Contrary to the results in Jurkat cells, PDTC did not inhibit tumor necrosis factor-alpha-induced NF kappaB activation in astrocytes; instead PDTC itself induces NF kappaB activation in astrocytes, and this may be related to scavenging of endogenously produced NO by the PDTC iron complex. In astrocytes PDTC also dramatically induces the NF kappaB-dependent enzyme, iNOS, supporting the physiologic relevance of endogenous NO regulation of NF kappaB. NF kappaB activation in glia from mice lacking nNOS responds more rapidly to PDTC compared with astrocytes from wild-type mice. Our data suggest that nNOS in astrocytes regulates NF kappaB activity and iNOS expression, and indicate a novel regulatory role for nNOS in tonically suppressing central nervous system, NF kappaB-regulated genes. " ], "offsets": [ [ 0, 1723 ] ] } ]

[ { "id": "9122255_T1", "type": "Protein", "text": [ "Neuronal (type I) nitric oxide synthase" ], "offsets": [ [ 0, 39 ] ], "normalized": [] }, { "id": "9122255_T2", "type": "Protein", "text": [ "immunologic (type II) nitric oxide synthase" ], "offsets": [ [ 85, 128 ] ], "normalized": [] }, { "id": "9122255_T3", "type": "Protein", "text": [ "neuronal NOS" ], "offsets": [ [ 287, 299 ] ], "normalized": [] }, { "id": "9122255_T4", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 301, 305 ] ], "normalized": [] }, { "id": "9122255_T5", "type": "Protein", "text": [ "endothelial NOS" ], "offsets": [ [ 308, 323 ] ], "normalized": [] }, { "id": "9122255_T6", "type": "Protein", "text": [ "immunologic NOS" ], "offsets": [ [ 329, 344 ] ], "normalized": [] }, { "id": "9122255_T7", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 346, 350 ] ], "normalized": [] }, { "id": "9122255_T8", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 366, 370 ] ], "normalized": [] }, { "id": "9122255_T9", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 448, 452 ] ], "normalized": [] }, { "id": "9122255_T10", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 834, 861 ] ], "normalized": [] }, { "id": "9122255_T11", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 863, 872 ] ], "normalized": [] }, { "id": "9122255_T12", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 992, 1019 ] ], "normalized": [] }, { "id": "9122255_T13", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 1297, 1301 ] ], "normalized": [] }, { "id": "9122255_T14", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 1429, 1433 ] ], "normalized": [] }, { "id": "9122255_T15", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 1532, 1536 ] ], "normalized": [] }, { "id": "9122255_T16", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 1584, 1588 ] ], "normalized": [] }, { "id": "9122255_T17", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 1642, 1646 ] ], "normalized": [] } ]

[ { "id": "9122255_E1", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 40, 49 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_E2" }, { "role": "Cause", "ref_id": "9122255_T1" } ] }, { "id": "9122255_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 129, 139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_T2" } ] }, { "id": "9122255_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 413, 422 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_T8" } ] }, { "id": "9122255_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1257, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_T13" } ] }, { "id": "9122255_E5", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1279, 1288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_T13" } ] }, { "id": "9122255_E6", "type": "Negative_regulation", "trigger": { "text": [ "lacking" ], "offsets": [ [ 1421, 1428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_T14" } ] }, { "id": "9122255_E7", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 1551, 1560 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_E8" }, { "role": "Cause", "ref_id": "9122255_T15" } ] }, { "id": "9122255_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1589, 1599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9122255_T16" } ] } ]

[ { "id": "9122255_1", "entity_ids": [ "9122255_T3", "9122255_T4" ] }, { "id": "9122255_2", "entity_ids": [ "9122255_T10", "9122255_T11" ] }, { "id": "9122255_3", "entity_ids": [ "9122255_T6", "9122255_T7" ] } ]

[]

[ { "id": "9428793__text", "type": "abstract", "text": [ "Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 (G0S2) in cultured human blood mononuclear cells. \nCyclosporin A (CsA) may achieve its immunosuppressive effects by inhibiting the calcium- and calmodulin-dependent phosphatase calcineurin which is required for activation of target genes by members of the NFAT (nuclear factor of activated T cells) transcription factor family. Among these target genes is the gene encoding interleukin-2 (IL2), a cytokine facilitating progression through the G1 phase of the cell cycle. However, IL2 does not reverse CsA inhibition, suggesting that at least one other NFAT-sensitive gene may be involved. The human G0/G1 switch gene, G0S2, has potential NFAT-binding sites in the 5' flank and encodes a small basic potential phosphoprotein of unknown function. Using a sensitive, reverse transcription-polymerase chain reaction (RT-PCR) assay, G0S2 mRNA levels were assayed in cultured blood mononuclear cells. Freshly isolated cells contain high levels of G0S2 mRNA which rapidly decline. This \"spontaneous stimulation\" is also noted with some other G0S genes and has been attributed to some aspect of the isolation procedure. In cells that have been preincubated to lower mRNA levels, there is a transient increase in G0S2 mRNA, peaking between 1-2 h, in response to Concanavalin-A (ConA), or to the combination of phorbol ester (TPA), and the calcium ionophore, ionomycin. Both these responses are inhibited by CsA. Our results suggest that G0S2 expression is required to commit cells to enter the G1 phase of the cell cycle, and that, while not excluding other possible targets, early inhibition of G0S2 expression by CsA may be important in achieving immunosuppression. G0S2 may be of value as a reporter gene for analyzing the mechanism of action of CsA and its influence on the positive and negative selection of lymphocytes in response to self and not-self antigens. " ], "offsets": [ [ 0, 1927 ] ] } ]

[ { "id": "9428793_T1", "type": "Protein", "text": [ "G0/G1 switch gene 2" ], "offsets": [ [ 48, 67 ] ], "normalized": [] }, { "id": "9428793_T2", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 69, 73 ] ], "normalized": [] }, { "id": "9428793_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 442, 455 ] ], "normalized": [] }, { "id": "9428793_T4", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "9428793_T5", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 548, 551 ] ], "normalized": [] }, { "id": "9428793_T6", "type": "Protein", "text": [ "G0/G1 switch gene" ], "offsets": [ [ 667, 684 ] ], "normalized": [] }, { "id": "9428793_T7", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 686, 690 ] ], "normalized": [] }, { "id": "9428793_T8", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 896, 900 ] ], "normalized": [] }, { "id": "9428793_T9", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 1009, 1013 ] ], "normalized": [] }, { "id": "9428793_T10", "type": "Protein", "text": [ "G0S" ], "offsets": [ [ 1103, 1106 ] ], "normalized": [] }, { "id": "9428793_T11", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 1272, 1276 ] ], "normalized": [] }, { "id": "9428793_T12", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 1496, 1500 ] ], "normalized": [] }, { "id": "9428793_T13", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 1655, 1659 ] ], "normalized": [] }, { "id": "9428793_T14", "type": "Protein", "text": [ "G0S2" ], "offsets": [ [ 1727, 1731 ] ], "normalized": [] } ]

[ { "id": "9428793_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 14, 22 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_E2" } ] }, { "id": "9428793_E2", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 29, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T2" } ] }, { "id": "9428793_E3", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 906, 912 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T8" } ] }, { "id": "9428793_E4", "type": "Positive_regulation", "trigger": { "text": [ "high" ], "offsets": [ [ 994, 998 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_E5" } ] }, { "id": "9428793_E5", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 999, 1005 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T9" } ] }, { "id": "9428793_E6", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1060, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T10" } ] }, { "id": "9428793_E7", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1260, 1268 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T11" } ] }, { "id": "9428793_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1453, 1462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_E7" } ] }, { "id": "9428793_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1501, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T12" } ] }, { "id": "9428793_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1641, 1651 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_E11" } ] }, { "id": "9428793_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1660, 1670 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9428793_T13" } ] } ]

[ { "id": "9428793_1", "entity_ids": [ "9428793_T1", "9428793_T2" ] }, { "id": "9428793_2", "entity_ids": [ "9428793_T3", "9428793_T4" ] }, { "id": "9428793_3", "entity_ids": [ "9428793_T6", "9428793_T7" ] } ]

[]

[ { "id": "1653056__text", "type": "abstract", "text": [ "NF-kappa B activation by tumor necrosis factor alpha in the Jurkat T cell line is independent of protein kinase A, protein kinase C, and Ca(2+)-regulated kinases. \nNF-kappa B is a DNA-binding regulatory factor able to control transcription of a number of genes, including human immunodeficiency virus (HIV) genes. In T cells, NF-kappa B is activated upon cellular treatment by phorbol esters and the cytokine tumor necrosis factor alpha (TNF alpha). In the present work, we investigated the molecular events leading to NF-kappa B activation by TNF alpha in a human T cell line (Jurkat) and its subclone JCT6, which presents a deficiency in the PKA transduction pathway. We found that in both cell lines, both phorbol ester and TNF alpha were able to activate NF-kappa B. Phorbol activation was positively modulated by Ca2+ influx while TNF alpha activation was not. Furthermore, while PMA activation was inhibited by the PKC inhibitor staurosporin, the TNF alpha effect was unchanged. TNF alpha did not activate cAMP production and its signal was not modulated by cAMP activators. Moreover, cAMP activators did not activate NF-kappa B in Jurkat cells. Thus, TNF alpha-induced NF-kappa B activation was found to be mediated by none of the major signal-mediating kinases such as protein kinase C (PKC), protein kinase A, or Ca(2+)-regulated kinases. Furthermore, we found that cytoplasmic acidification facilitated NF-kappa B activation by both TNF alpha and PKC, by a mechanism that increases NF-kappa B/I kappa B dissociation without affecting the NF-kappa B translocation step. " ], "offsets": [ [ 0, 1579 ] ] } ]

[ { "id": "1653056_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 25, 52 ] ], "normalized": [] }, { "id": "1653056_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 409, 436 ] ], "normalized": [] }, { "id": "1653056_T3", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 438, 447 ] ], "normalized": [] }, { "id": "1653056_T4", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 544, 553 ] ], "normalized": [] }, { "id": "1653056_T5", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 727, 736 ] ], "normalized": [] }, { "id": "1653056_T6", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 836, 845 ] ], "normalized": [] }, { "id": "1653056_T7", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 953, 962 ] ], "normalized": [] }, { "id": "1653056_T8", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 985, 994 ] ], "normalized": [] }, { "id": "1653056_T9", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1158, 1167 ] ], "normalized": [] }, { "id": "1653056_T10", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1443, 1452 ] ], "normalized": [] } ]

[]

[ { "id": "1653056_1", "entity_ids": [ "1653056_T2", "1653056_T3" ] } ]

[]

[ { "id": "2148290__text", "type": "abstract", "text": [ "Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs. \nA primary site of infection by human adenoviruses is lymphoid cells. However, analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported. The adenovirus early region 3 (ES) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens, thus preventing their cell surface expression with a resultant decrease in host immunologic destruction. To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells, both DNA binding and transfection analysis with the E3 promoter in both cell types were performed. These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts. Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B. Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif (L2) had minimal effects on promoter expression in HeLa cells, but resulted in dramatic decreases in expression by lymphoid cells. In contrast, mutagenesis of proximal NF-kappa B motif (L1) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small, but reproducible, increase in gene expression in lymphoid cells when coupled to the L2 mutation. Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1827 ] ] } ]

[ { "id": "2148290_T1", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1090, 1123 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "9731697__text", "type": "abstract", "text": [ "Retinoid X receptor and c-cerbA/thyroid hormone receptor regulate erythroid cell growth and differentiation. \nNuclear receptors are important regulators of erythroid cell development. Here we investigated the impact of retinoid X receptor (RXR), retinoic acid receptor (RAR), and of the c-erbA/thyroid hormone (T3) receptor (c-erbA/TR) on growth and differentiation of erythroid cells using an in vitro culture system of stem cell factor-dependent erythroid progenitors. RXR, RAR, and c-erbA/TR-specific ligands were found to induce erythroid-specific gene expression and to accelerate erythroid differentiation in culture, with T3 being most effective. Furthermore, while ligand-activated c-erbA/TR accelerated differentiation, unliganded c-erbA/TR effectively blocked differentiation and supported sustained progenitor growth in culture. Thus, c-erbA/TR appears to act as a binary switch affecting erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation. Additionally, to determine the impact of RXR for erythroid cell development, dominant interfering mutant RXRs, lacking the transcriptional activator functions AF-1 and AF-2, or AF-2 only, or the entire DNA-binding domain, were introduced into erythroid progenitor cells via recombinant retrovirus vectors and analyzed for RXR-specific effects. It was found that expression of wild-type RXR and of the RXR mutants devoid of AF-1 and/or AF-2 supported a transient outgrowth of erythroid cells. In marked contrast, expression of the dominant interfering deltaDNA-binding domain RXR, containing a deletion of the entire DNA-binding domain, was incompatible with erythroid cell growth in vitro, suggesting a pivotal role of RXR for erythroid cell development. " ], "offsets": [ [ 0, 1771 ] ] } ]

[ { "id": "9731697_T1", "type": "Protein", "text": [ "stem cell factor" ], "offsets": [ [ 421, 437 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "10425262__text", "type": "abstract", "text": [ "Reactive oxygen intermediate-release of fibre-exposed monocytes increases inflammatory cytokine-mRNA level, protein tyrosine kinase and NF-kappaB activity in co-cultured bronchial epithelial cells (BEAS-2B). \nSome pulmonary diseases like bronchitis or asthma bronchiale are mediated by inflammatory mechanisms in bronchial epithelial cells. Alveolar macrophages are located directly in the surrounding of these cells, so that we suppose an interaction between epithelial cells and macrophages regarding to the release of inflammatory mediators. For measuring the contribution of macrophages to the release of inflammatory mediators by bronchial epithelial cells, we established an in vitro model of co-cultured blood monocytes (BM) and BEAS-2B cells in a transwell system (Costar). BM were exposed to Chrysotile B and soot particle FR 101 in a concentration of 100 microg/10(6) cells. After up to 90 min exposure time ELISA, EMSA (electromobility shift assay) and RT-PCR were used to measure protein tyrosine kinase activity, protein activity of NF-kappaB and cytokine (IL-1beta, IL-6, TNF-alpha) specific mRNA levels in BEAS-2B cells. We observed an increase in protein tyrosine kinase activity (up to 1.8 +/- 0.5-fold) and NF-kappaB protein activity in BEAS-2B cells after particle or fibre exposure of co-cultured BM. Consecutive IL-1beta-, IL-6- and TNF-alpha-mRNA were elevated (up to 1.9 +/- 0.58-fold). Protein tyrosine kinase activity, NF-kappaB activity, and the synthesis of cytokine-specific mRNA were inhibited by antioxidants. These data suggest a ROI-dependent NF-kappaB mediated transcription of inflammatory cytokines in bronchial epithelial cells. " ], "offsets": [ [ 0, 1665 ] ] } ]

[ { "id": "10425262_T1", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1070, 1078 ] ], "normalized": [] }, { "id": "10425262_T2", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1080, 1084 ] ], "normalized": [] }, { "id": "10425262_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1086, 1095 ] ], "normalized": [] }, { "id": "10425262_T4", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1333, 1341 ] ], "normalized": [] }, { "id": "10425262_T5", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1344, 1348 ] ], "normalized": [] }, { "id": "10425262_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1354, 1363 ] ], "normalized": [] } ]

[ { "id": "10425262_E1", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 1374, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10425262_T5" } ] }, { "id": "10425262_E2", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 1374, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10425262_T6" } ] }, { "id": "10425262_E3", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 1374, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10425262_T4" } ] } ]

[]

[]

[ { "id": "7964516__text", "type": "abstract", "text": [ "Functional Myc-Max heterodimer is required for activation-induced apoptosis in T cell hybridomas. \nT cell hybridomas respond to activation signals by undergoing apoptotic cell death, and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo. Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis. This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner, Max, which we show here inhibits activation-induced apoptosis. Further, coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis. These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max, and therefore, by regulating gene transcription. " ], "offsets": [ [ 0, 1000 ] ] } ]

[ { "id": "7964516_T1", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 11, 14 ] ], "normalized": [] }, { "id": "7964516_T2", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 15, 18 ] ], "normalized": [] }, { "id": "7964516_T3", "type": "Protein", "text": [ "c-Myc" ], "offsets": [ [ 369, 374 ] ], "normalized": [] }, { "id": "7964516_T4", "type": "Protein", "text": [ "c-Myc" ], "offsets": [ [ 448, 453 ] ], "normalized": [] }, { "id": "7964516_T5", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "7964516_T6", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 674, 677 ] ], "normalized": [] }, { "id": "7964516_T7", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 745, 748 ] ], "normalized": [] }, { "id": "7964516_T8", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 866, 869 ] ], "normalized": [] }, { "id": "7964516_T9", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 946, 949 ] ], "normalized": [] } ]

[ { "id": "7964516_E1", "type": "Binding", "trigger": { "text": [ "binding partner" ], "offsets": [ [ 547, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7964516_T4" }, { "role": "Theme", "ref_id": "7964516_T5" } ] }, { "id": "7964516_E2", "type": "Gene_expression", "trigger": { "text": [ "coexpression" ], "offsets": [ [ 636, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7964516_T7" } ] }, { "id": "7964516_E3", "type": "Gene_expression", "trigger": { "text": [ "coexpression" ], "offsets": [ [ 636, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7964516_T6" } ] }, { "id": "7964516_E4", "type": "Binding", "trigger": { "text": [ "capable of forming functional heterodimers" ], "offsets": [ [ 686, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7964516_T6" }, { "role": "Theme", "ref_id": "7964516_T7" } ] }, { "id": "7964516_E5", "type": "Binding", "trigger": { "text": [ "heterodimerization" ], "offsets": [ [ 922, 940 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7964516_T8" }, { "role": "Theme", "ref_id": "7964516_T9" } ] } ]

[]

[]

[ { "id": "1899335__text", "type": "abstract", "text": [ "Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes. \nWe have found that purified human peripheral-blood granulocytes express constitutively significant levels of proto-oncogenes c-jun, jun B and jun D mRNA. Upon functional activation of granulocytes by 4 beta-phorbol 12-myristate 13-acetate (PMA), the levels of c-jun, jun B and jun D transcripts were increased. The three jun genes showed a similar time course in their induction by PMA, maximal mRNA levels being reached after 60 min of induction. These results suggest that expression of c-jun, jun B and jun D genes might be involved in terminal granulocyte differentiation or in regulating granulocyte functionality. " ], "offsets": [ [ 0, 714 ] ] } ]

[ { "id": "1899335_T1", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "1899335_T2", "type": "Protein", "text": [ "jun B" ], "offsets": [ [ 21, 26 ] ], "normalized": [] }, { "id": "1899335_T3", "type": "Protein", "text": [ "jun D" ], "offsets": [ [ 31, 36 ] ], "normalized": [] }, { "id": "1899335_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 219, 224 ] ], "normalized": [] }, { "id": "1899335_T5", "type": "Protein", "text": [ "jun B" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "1899335_T6", "type": "Protein", "text": [ "jun D" ], "offsets": [ [ 236, 241 ] ], "normalized": [] }, { "id": "1899335_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 354, 359 ] ], "normalized": [] }, { "id": "1899335_T8", "type": "Protein", "text": [ "jun B" ], "offsets": [ [ 361, 366 ] ], "normalized": [] }, { "id": "1899335_T9", "type": "Protein", "text": [ "jun D" ], "offsets": [ [ 371, 376 ] ], "normalized": [] }, { "id": "1899335_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 583, 588 ] ], "normalized": [] }, { "id": "1899335_T11", "type": "Protein", "text": [ "jun B" ], "offsets": [ [ 590, 595 ] ], "normalized": [] }, { "id": "1899335_T12", "type": "Protein", "text": [ "jun D" ], "offsets": [ [ 600, 605 ] ], "normalized": [] } ]

[ { "id": "1899335_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T2" } ] }, { "id": "1899335_E2", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T3" } ] }, { "id": "1899335_E3", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T1" } ] }, { "id": "1899335_E4", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 158, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T6" } ] }, { "id": "1899335_E5", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 158, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T4" } ] }, { "id": "1899335_E6", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 158, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T5" } ] }, { "id": "1899335_E7", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 344, 350 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T9" } ] }, { "id": "1899335_E8", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 344, 350 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T7" } ] }, { "id": "1899335_E9", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 344, 350 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T8" } ] }, { "id": "1899335_E10", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 394, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_E9" } ] }, { "id": "1899335_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 394, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_E8" } ] }, { "id": "1899335_E12", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 394, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_E7" } ] }, { "id": "1899335_E13", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 463, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T9" } ] }, { "id": "1899335_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 463, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T7" } ] }, { "id": "1899335_E15", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 463, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T8" } ] }, { "id": "1899335_E16", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 489, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T7" } ] }, { "id": "1899335_E17", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 489, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T9" } ] }, { "id": "1899335_E18", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 489, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T8" } ] }, { "id": "1899335_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 569, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T10" } ] }, { "id": "1899335_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 569, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T11" } ] }, { "id": "1899335_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 569, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1899335_T12" } ] } ]

[]

[]

[ { "id": "10364260__text", "type": "abstract", "text": [ "Human alveolar macrophages are markedly deficient in REF-1 and AP-1 DNA binding activity. \nAlthough many functions of human alveolar macrophages are altered compared with their precursor cell, the blood monocyte (monocyte), the reason(s) for these functional changes have not been determined. We recently reported that human alveolar macrophages do not express AP-1 DNA binding activity (Monick, M. M., Carter, A. B., Gudmundsson, G., Geist, L. J., and Hunninghake, G. W. (1998) Am. J. Physiol. 275, L389-L397). To determine why alveolar macrophages do not express AP-1 DNA binding activity, we first showed that there was not a decrease in expression of the FOS and JUN proteins that make up the AP-1 complex. There was, however, a significant difference in the amounts of the nuclear protein, REF-1 (which regulates AP-1 DNA binding by altering the redox status of FOS and JUN proteins), in alveolar macrophages compared with monocytes. In addition, in vitro differentiation of monocytes to a macrophage-like cell resulted in decreased amounts of REF-1. Finally, addition of REF-1 from activated monocytes to alveolar macrophage nuclear proteins resulted in a marked increase in AP-1 DNA binding. These studies strongly suggest that the process of differentiation of monocytes into alveolar macrophages is associated with a loss of REF-1 and AP-1 activity. This observation may explain, in part, some of the functional differences observed for alveolar macrophages compared with monocytes. " ], "offsets": [ [ 0, 1492 ] ] } ]

[ { "id": "10364260_T1", "type": "Protein", "text": [ "REF-1" ], "offsets": [ [ 53, 58 ] ], "normalized": [] }, { "id": "10364260_T2", "type": "Protein", "text": [ "REF-1" ], "offsets": [ [ 795, 800 ] ], "normalized": [] }, { "id": "10364260_T3", "type": "Protein", "text": [ "REF-1" ], "offsets": [ [ 1049, 1054 ] ], "normalized": [] }, { "id": "10364260_T4", "type": "Protein", "text": [ "REF-1" ], "offsets": [ [ 1077, 1082 ] ], "normalized": [] }, { "id": "10364260_T5", "type": "Protein", "text": [ "REF-1" ], "offsets": [ [ 1334, 1339 ] ], "normalized": [] } ]

[ { "id": "10364260_E1", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 40, 49 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10364260_E2" } ] }, { "id": "10364260_E2", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 72, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10364260_T1" } ] }, { "id": "10364260_E3", "type": "Gene_expression", "trigger": { "text": [ "in the amounts" ], "offsets": [ [ 756, 770 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10364260_T2" } ] }, { "id": "10364260_E4", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1028, 1037 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10364260_T3" } ] }, { "id": "10364260_E5", "type": "Negative_regulation", "trigger": { "text": [ "loss" ], "offsets": [ [ 1326, 1330 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "10364260_T5" } ] } ]

[]

[]

[ { "id": "1953785__text", "type": "abstract", "text": [ "Regulation of interleukin-1 beta production by glucocorticoids in human monocytes: the mechanism of action depends on the activation signal. \nGlucocorticoids are known to downregulate interleukin-1 beta production in monocytic cells by two different mechanims: direct inhibition of the gene transcription and destabilization of the preformed interleukin-1 beta mRNA. Now we have examined the effect of the nature of the monocyte activating signal on these two inhibitory mechanims. When human monocytes were preincubated with dexamethasone for 1 hour and then stimulated either with bacterial lipopolysaccharide or phorbol myristate, it was found that dexamethasone inhibited the lipopolysaccharide-induced interleukin-1 beta protein production, but the phorbol myristate-induced production was increased 3-10 fold. This difference was also seen at the mRNA level. When dexamethasone was added to the cultures 3 hours after the stimulators, it clearly decreased the interleukin-1 beta mRNA levels regardless of the stimulator used (although the effect was clearly weaker on the PMA-induced mRNA). Thus these data suggest that the phorbol myristate-induced signal (prolonged protein kinase C activation?) cannot be inhibited by prior incubation with dexamethasone and it also protects the induced mRNA for the degradative action of dexamethasone. " ], "offsets": [ [ 0, 1346 ] ] } ]

[ { "id": "1953785_T1", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 14, 32 ] ], "normalized": [] }, { "id": "1953785_T2", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 184, 202 ] ], "normalized": [] }, { "id": "1953785_T3", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 342, 360 ] ], "normalized": [] }, { "id": "1953785_T4", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 707, 725 ] ], "normalized": [] }, { "id": "1953785_T5", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 966, 984 ] ], "normalized": [] } ]

[ { "id": "1953785_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E2" } ] }, { "id": "1953785_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 33, 43 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T1" } ] }, { "id": "1953785_E3", "type": "Regulation", "trigger": { "text": [ "depends" ], "offsets": [ [ 107, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E1" } ] }, { "id": "1953785_E4", "type": "Negative_regulation", "trigger": { "text": [ "downregulate" ], "offsets": [ [ 171, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E6" } ] }, { "id": "1953785_E5", "type": "Negative_regulation", "trigger": { "text": [ "downregulate" ], "offsets": [ [ 171, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E6" }, { "role": "Cause", "ref_id": "1953785_E7" } ] }, { "id": "1953785_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 203, 213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T2" } ] }, { "id": "1953785_E7", "type": "Negative_regulation", "trigger": { "text": [ "destabilization" ], "offsets": [ [ 309, 324 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T3" } ] }, { "id": "1953785_E8", "type": "Transcription", "trigger": { "text": [ "preformed" ], "offsets": [ [ 332, 341 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T3" } ] }, { "id": "1953785_E9", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 392, 398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E7" } ] }, { "id": "1953785_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 666, 675 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E11" } ] }, { "id": "1953785_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 699, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E12" } ] }, { "id": "1953785_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 734, 744 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T4" } ] }, { "id": "1953785_E13", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 772, 779 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E12" } ] }, { "id": "1953785_E14", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 795, 804 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E13" } ] }, { "id": "1953785_E15", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 952, 961 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E16" } ] }, { "id": "1953785_E16", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 990, 996 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T5" } ] }, { "id": "1953785_E17", "type": "Regulation", "trigger": { "text": [ "regardless of" ], "offsets": [ [ 997, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E15" } ] }, { "id": "1953785_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1082, 1089 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T5" } ] }, { "id": "1953785_E19", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1148, 1155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_T5" } ] }, { "id": "1953785_E20", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1214, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1953785_E19" } ] } ]

[]

[]

[ { "id": "9144479__text", "type": "abstract", "text": [ "CD40 is a functional activation antigen and B7-independent T cell costimulatory molecule on normal human lung fibroblasts. \nCD40 is an important signaling and activation Ag found on certain bone marrow-derived cells. Recently, CD40 also has been shown to be expressed by mesenchymal cells, including human fibroblasts. Little is known about the role of CD40 in fibroblasts. The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activation structure and mechanism for interaction with hemopoietic cells. Communication between resident tissue fibroblasts and T cells is necessary for normal wound healing, and can be pathologic, resulting in tissue fibrosis. Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation, as evidenced by mobilization of nuclear factor-kappaB and by induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8. IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40, but not the well-studied costimulatory molecules B7-1 and B7-2. Data reported herein support the hypothesis that cognate interactions between tissue fibroblasts and infiltrating T lymphocytes, via the CD40/CD40L pathway, augment inflammation and may promote fibrogenesis by activating both cell types. " ], "offsets": [ [ 0, 1307 ] ] } ]

[ { "id": "9144479_T1", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "9144479_T2", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 44, 46 ] ], "normalized": [] }, { "id": "9144479_T3", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 124, 128 ] ], "normalized": [] }, { "id": "9144479_T4", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 227, 231 ] ], "normalized": [] }, { "id": "9144479_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 353, 357 ] ], "normalized": [] }, { "id": "9144479_T6", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 425, 429 ] ], "normalized": [] }, { "id": "9144479_T7", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 713, 717 ] ], "normalized": [] }, { "id": "9144479_T8", "type": "Protein", "text": [ "CD40 ligand" ], "offsets": [ [ 731, 742 ] ], "normalized": [] }, { "id": "9144479_T9", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 901, 905 ] ], "normalized": [] }, { "id": "9144479_T10", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 910, 914 ] ], "normalized": [] }, { "id": "9144479_T11", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 916, 925 ] ], "normalized": [] }, { "id": "9144479_T12", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 999, 1003 ] ], "normalized": [] }, { "id": "9144479_T13", "type": "Protein", "text": [ "B7-1" ], "offsets": [ [ 1054, 1058 ] ], "normalized": [] }, { "id": "9144479_T14", "type": "Protein", "text": [ "B7-2" ], "offsets": [ [ 1063, 1067 ] ], "normalized": [] }, { "id": "9144479_T15", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1206, 1210 ] ], "normalized": [] }, { "id": "9144479_T16", "type": "Protein", "text": [ "CD40L" ], "offsets": [ [ 1211, 1216 ] ], "normalized": [] } ]

[ { "id": "9144479_E1", "type": "Gene_expression", "trigger": { "text": [ "found" ], "offsets": [ [ 173, 178 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9144479_T3" } ] }, { "id": "9144479_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 258, 267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9144479_T4" } ] }, { "id": "9144479_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 430, 439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9144479_T6" } ] }, { "id": "9144479_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 838, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9144479_T9" } ] }, { "id": "9144479_E5", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 838, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9144479_T10" } ] } ]

[]

[]

[ { "id": "8468462__text", "type": "abstract", "text": [ "Costimulation of peripheral blood T cell activation by human endothelial cells. Enhanced IL-2 transcription correlates with increased c-fos synthesis and increased Fos content of AP-1. \nEndothelial cells (EC) act as APC for resting PBL in vitro, and may have important roles in vivo in the pathogenesis of allograft rejection and delayed hypersensitivity. We previously reported that human umbilical vein EC provide costimulatory signals to PHA-stimulated PBL via CD2:lymphocyte function-associated Ag-3 and an unidentified ligand pair, resulting in a three- to eight-fold enhancement of IL-2 production. The physiologic relevance of this increase was demonstrated by the proliferative advantage provided by EC to PBL suboptimally stimulated with mAb OKT3. We now report that EC costimulation causes increased levels of IL-2 mRNA as a result of increased IL-2 transcription in PBL. We therefore examined the effects of EC on T cell nuclear factors known to regulate IL-2 transcription, including c-jun and c-fos-two components of the transcription factor AP-1, NFAT, and others. PBL constitutively express c-jun transcripts, and the level of c-jun mRNA is not altered by PHA activation in the absence or presence of EC. In contrast, c-fos mRNA is absent from resting T cells and is induced on PHA activation. EC alone do not induce c-fos mRNA but augment the level of c-fos mRNA in PHA-activated T cells by 3- to 10-fold. This effect is largely independent of the CD2:lymphocyte function-associated Ag-3 pathway. Gel-shift analysis reveals the constitutive presence of nuclear factors in resting PBL that bind to the proximal AP-1 site of the IL-2 promoter and that contain immunoreactive c-Jun but not c-Fos protein. In contrast, AP-1 from PHA-activated cells contains c-Jun and low levels of c-Fos. Strikingly, costimulation with EC results in a dramatic increase (up to 15-fold) in the c-Fos content of AP-1. Levels of other nuclear factors involved in IL-2 regulation were not altered by EC, although NFAT-DNA complexes migrated at a slightly different mobility. In summary, our data suggest that changes in the composition of transcription factor AP-1 is a key molecular mechanism for increasing IL-2 transcription and may underlie the phenomenon of costimulation by EC. " ], "offsets": [ [ 0, 2276 ] ] } ]

[ { "id": "8468462_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "8468462_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 134, 139 ] ], "normalized": [] }, { "id": "8468462_T3", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 441, 444 ] ], "normalized": [] }, { "id": "8468462_T4", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "8468462_T5", "type": "Protein", "text": [ "lymphocyte function-associated Ag-3" ], "offsets": [ [ 468, 503 ] ], "normalized": [] }, { "id": "8468462_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 588, 592 ] ], "normalized": [] }, { "id": "8468462_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 820, 824 ] ], "normalized": [] }, { "id": "8468462_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 855, 859 ] ], "normalized": [] }, { "id": "8468462_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 966, 970 ] ], "normalized": [] }, { "id": "8468462_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 996, 1001 ] ], "normalized": [] }, { "id": "8468462_T11", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1006, 1011 ] ], "normalized": [] }, { "id": "8468462_T12", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1106, 1111 ] ], "normalized": [] }, { "id": "8468462_T13", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1142, 1147 ] ], "normalized": [] }, { "id": "8468462_T14", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1171, 1174 ] ], "normalized": [] }, { "id": "8468462_T15", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "8468462_T16", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1293, 1296 ] ], "normalized": [] }, { "id": "8468462_T17", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1332, 1337 ] ], "normalized": [] }, { "id": "8468462_T18", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1368, 1373 ] ], "normalized": [] }, { "id": "8468462_T19", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1382, 1385 ] ], "normalized": [] }, { "id": "8468462_T20", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1464, 1467 ] ], "normalized": [] }, { "id": "8468462_T21", "type": "Protein", "text": [ "lymphocyte function-associated Ag-3" ], "offsets": [ [ 1468, 1503 ] ], "normalized": [] }, { "id": "8468462_T22", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1643, 1647 ] ], "normalized": [] }, { "id": "8468462_T23", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1689, 1694 ] ], "normalized": [] }, { "id": "8468462_T24", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1703, 1708 ] ], "normalized": [] }, { "id": "8468462_T25", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1741, 1744 ] ], "normalized": [] }, { "id": "8468462_T26", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1770, 1775 ] ], "normalized": [] }, { "id": "8468462_T27", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1794, 1799 ] ], "normalized": [] }, { "id": "8468462_T28", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1889, 1894 ] ], "normalized": [] }, { "id": "8468462_T29", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1956, 1960 ] ], "normalized": [] }, { "id": "8468462_T30", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 2201, 2205 ] ], "normalized": [] }, { "id": "8468462_T53", "type": "Entity", "text": [ "proximal AP-1 site" ], "offsets": [ [ 1617, 1635 ] ], "normalized": [] } ]

[ { "id": "8468462_E1", "type": "Positive_regulation", "trigger": { "text": [ "Enhanced" ], "offsets": [ [ 80, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E2" } ] }, { "id": "8468462_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 94, 107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T1" } ] }, { "id": "8468462_E3", "type": "Binding", "trigger": { "text": [ "content of AP-1" ], "offsets": [ [ 168, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T5" } ] }, { "id": "8468462_E4", "type": "Positive_regulation", "trigger": { "text": [ "provide costimulatory signals" ], "offsets": [ [ 408, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E7" } ] }, { "id": "8468462_E5", "type": "Positive_regulation", "trigger": { "text": [ "provide costimulatory signals" ], "offsets": [ [ 408, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E6" } ] }, { "id": "8468462_E6", "type": "Binding", "trigger": { "text": [ ":" ], "offsets": [ [ 467, 468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T4" }, { "role": "Theme", "ref_id": "8468462_T5" } ] }, { "id": "8468462_E7", "type": "Binding", "trigger": { "text": [ "pair" ], "offsets": [ [ 531, 535 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T4" } ] }, { "id": "8468462_E8", "type": "Positive_regulation", "trigger": { "text": [ "enhancement" ], "offsets": [ [ 573, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E9" } ] }, { "id": "8468462_E9", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 593, 603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T6" } ] }, { "id": "8468462_E10", "type": "Positive_regulation", "trigger": { "text": [ "causes" ], "offsets": [ [ 793, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E11" }, { "role": "Cause", "ref_id": "8468462_E12" } ] }, { "id": "8468462_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 800, 809 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T7" } ] }, { "id": "8468462_E12", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 845, 854 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E13" } ] }, { "id": "8468462_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 860, 873 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T8" } ] }, { "id": "8468462_E14", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 908, 915 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T10" } ] }, { "id": "8468462_E15", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 908, 915 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T11" } ] }, { "id": "8468462_E16", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E18" }, { "role": "Cause", "ref_id": "8468462_T11" } ] }, { "id": "8468462_E17", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E18" }, { "role": "Cause", "ref_id": "8468462_T10" } ] }, { "id": "8468462_E18", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 971, 984 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T9" } ] }, { "id": "8468462_E19", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1098, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T12" } ] }, { "id": "8468462_E20", "type": "Regulation", "trigger": { "text": [ "altered" ], "offsets": [ [ 1160, 1167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T13" } ] }, { "id": "8468462_E21", "type": "Transcription", "trigger": { "text": [ "absent" ], "offsets": [ [ 1247, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T15" } ] }, { "id": "8468462_E22", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1282, 1289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T15" } ] }, { "id": "8468462_E23", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1325, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T17" } ] }, { "id": "8468462_E24", "type": "Positive_regulation", "trigger": { "text": [ "augment" ], "offsets": [ [ 1347, 1354 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T18" } ] }, { "id": "8468462_E25", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1605, 1609 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T22" }, { "role": "Site", "ref_id": "8468462_T53" } ] }, { "id": "8468462_E26", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1944, 1952 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E27" } ] }, { "id": "8468462_E27", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1961, 1971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T29" } ] }, { "id": "8468462_E28", "type": "Regulation", "trigger": { "text": [ "is a key molecular mechanism" ], "offsets": [ [ 2157, 2185 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E29" }, { "role": "Cause", "ref_id": "8468462_E30" } ] }, { "id": "8468462_E29", "type": "Positive_regulation", "trigger": { "text": [ "increasing" ], "offsets": [ [ 2190, 2200 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_E30" } ] }, { "id": "8468462_E30", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 2206, 2219 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "8468462_T30" } ] } ]

[]

[]

[ { "id": "9343210__text", "type": "abstract", "text": [ "Transcriptional activation of the vascular cell adhesion molecule-1 gene in T lymphocytes expressing human T-cell leukemia virus type 1 Tax protein. \nRecruitment and extravasation of T cells through the blood-brain barrier are favored by adhesion molecule-mediated interactions of circulating T cells with endothelial cells. Since a common pathological finding in human T-cell leukemia virus type 1 (HTLV-1)-associated diseases is the infiltration of HTLV-1-infected T lymphocytes into various organs, we have looked for the profile of adhesion molecules expressed by HTLV-1-transformed T cells. Flow cytometry analysis indicated that these cells were expressing high levels of vascular cell adhesion molecule 1 (VCAM-1 [CD106]), a 110-kDa member of the immunoglobulin gene superfamily, first identified on endothelial cells stimulated with inflammatory cytokines. This adhesion molecule was also expressed by T cells obtained from one patient with HTLV-1-associated myelopathy/tropical spastic paraparesis but not by activated T cells isolated from one normal blood donor. The role of the viral trans-activator Tax protein in the induction of VCAM-1 was first indicated by the detection of this adhesion molecule on Jurkat T-cell clones stably expressing the tax gene. The effect of Tax on VCAM-1 gene transcription was next confirmed in JPX-9 cells, a subclone of Jurkat cells, carrying the tax sequences under the control of an inducible promoter. Furthermore, deletion and mutation analyses of the VCAM-1 promoter performed with chloramphenicol acetyltransferase constructs revealed that Tax was trans activating the VCAM-1 promoter via two NF-kappaB sites present at bp -72 and -57 in the VCAM-1 gene promoter, with both of them being required for the Tax-induced expression of this adhesion molecule. Finally, gel mobility shift assays demonstrated the nuclear translocation of proteins specifically bound to these two NF-kappaB motifs, confirming that VCAM-1 was induced on Tax-expressing cells in a kappaB-dependent manner. Collectively, these results therefore suggest that the exclusive Tax-induced expression of VCAM-1 on T cells may represent a pivotal event in the progression of HTLV-1-associated diseases. " ], "offsets": [ [ 0, 2221 ] ] } ]

[ { "id": "9343210_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 34, 67 ] ], "normalized": [] }, { "id": "9343210_T2", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 136, 139 ] ], "normalized": [] }, { "id": "9343210_T3", "type": "Protein", "text": [ "vascular cell adhesion molecule 1" ], "offsets": [ [ 678, 711 ] ], "normalized": [] }, { "id": "9343210_T4", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 713, 719 ] ], "normalized": [] }, { "id": "9343210_T5", "type": "Protein", "text": [ "CD106" ], "offsets": [ [ 721, 726 ] ], "normalized": [] }, { "id": "9343210_T6", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1112, 1115 ] ], "normalized": [] }, { "id": "9343210_T7", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "9343210_T8", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] }, { "id": "9343210_T9", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1284, 1287 ] ], "normalized": [] }, { "id": "9343210_T10", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1291, 1297 ] ], "normalized": [] }, { "id": "9343210_T11", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 1393, 1396 ] ], "normalized": [] }, { "id": "9343210_T12", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1502, 1508 ] ], "normalized": [] }, { "id": "9343210_T13", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1533, 1566 ] ], "normalized": [] }, { "id": "9343210_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1592, 1595 ] ], "normalized": [] }, { "id": "9343210_T15", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1621, 1627 ] ], "normalized": [] }, { "id": "9343210_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1694, 1700 ] ], "normalized": [] }, { "id": "9343210_T17", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1757, 1760 ] ], "normalized": [] }, { "id": "9343210_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1959, 1965 ] ], "normalized": [] }, { "id": "9343210_T19", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1981, 1984 ] ], "normalized": [] }, { "id": "9343210_T20", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 2097, 2100 ] ], "normalized": [] }, { "id": "9343210_T21", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 2123, 2129 ] ], "normalized": [] }, { "id": "9343210_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1628, 1636 ] ], "normalized": [] }, { "id": "9343210_T37", "type": "Entity", "text": [ "NF-kappaB sites" ], "offsets": [ [ 1645, 1660 ] ], "normalized": [] } ]

[ { "id": "9343210_E1", "type": "Positive_regulation", "trigger": { "text": [ "Transcriptional activation" ], "offsets": [ [ 0, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T1" } ] }, { "id": "9343210_E2", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 90, 100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T2" } ] }, { "id": "9343210_E3", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 652, 662 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T4" } ] }, { "id": "9343210_E4", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 663, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E3" } ] }, { "id": "9343210_E5", "type": "Gene_expression", "trigger": { "text": [ "identified" ], "offsets": [ [ 793, 803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T4" } ] }, { "id": "9343210_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 897, 906 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T4" } ] }, { "id": "9343210_E7", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1078, 1082 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E8" }, { "role": "Cause", "ref_id": "9343210_T6" } ] }, { "id": "9343210_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1131, 1140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T7" } ] }, { "id": "9343210_E9", "type": "Gene_expression", "trigger": { "text": [ "detection" ], "offsets": [ [ 1178, 1187 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T7" } ] }, { "id": "9343210_E10", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1245, 1255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T8" } ] }, { "id": "9343210_E11", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1274, 1280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E12" }, { "role": "Cause", "ref_id": "9343210_T9" } ] }, { "id": "9343210_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1303, 1316 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T10" } ] }, { "id": "9343210_E13", "type": "Positive_regulation", "trigger": { "text": [ "trans activating" ], "offsets": [ [ 1600, 1616 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T15" }, { "role": "Cause", "ref_id": "9343210_E14" }, { "role": "Site", "ref_id": "9343210_T35" } ] }, { "id": "9343210_E14", "type": "Binding", "trigger": { "text": [ "via" ], "offsets": [ [ 1637, 1640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T14" }, { "role": "Theme", "ref_id": "9343210_T16" }, { "role": "Site", "ref_id": "9343210_T37" } ] }, { "id": "9343210_E15", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1740, 1748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E16" }, { "role": "Cause", "ref_id": "9343210_T16" }, { "role": "CSite", "ref_id": "9343210_T37" } ] }, { "id": "9343210_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1761, 1768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E17" }, { "role": "Cause", "ref_id": "9343210_T17" } ] }, { "id": "9343210_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1769, 1779 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T16" } ] }, { "id": "9343210_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1970, 1977 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T18" } ] }, { "id": "9343210_E19", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1985, 1995 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T19" } ] }, { "id": "9343210_E20", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 2014, 2023 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E18" } ] }, { "id": "9343210_E21", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2101, 2108 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_E22" }, { "role": "Cause", "ref_id": "9343210_T20" } ] }, { "id": "9343210_E22", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2109, 2119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "9343210_T21" } ] } ]

[]

[]

[ { "id": "8723387__text", "type": "abstract", "text": [ "Gene transcription through activation of G-protein-coupled chemoattractant receptors. \nReceptors for leukocyte chemoattractants, including chemokines, are traditionally considered to be responsible for the activation of special leukocyte functions such as chemotaxis, degranulation, and the release of superoxide anions. Recently, these G-protein-coupled serpentine receptors have been found to transduce signals leading to gene transcription and translation in leukocytes. Transcription factors, such as NF kappa B and AP-1, are activated upon stimulation of the cells with several chemoattractants at physiologically relevant concentrations. Activation of transcription factors through these receptors involves G-protein coupling and the activation of protein kinases. The underlying signaling pathways appear to be different from those utilized by TNF-alpha, a better characterized cytokine that induces the transcription of immediate-early genes. Chemoattractants stimulate the expression of several inflammatory cytokines and chemokines, which in turn may activate their respective receptors and initiate an autocrine regulatory mechanism for persistent cytokine and chemokine gene expression. " ], "offsets": [ [ 0, 1199 ] ] } ]

[ { "id": "8723387_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 851, 860 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "8428943__text", "type": "abstract", "text": [ "ras protein activity is essential for T-cell antigen receptor signal transduction. \nIn a Jurkat cell model of T-cell activation an interleukin-2 promoter/reporter gene construct was activated by antigen receptor agonism in combination with the lymphokine interleukin-1. Antigen receptor signals could be mimicked by suboptimal activation of protein kinase C (PKC) with phorbol esters in combination with calcium mobilization by an ionophore. In cotransfection experiments, oncogenic rats obviated the need for PKC stimulation but did not replace either the calcium signal or interleukin-1. Activated ras expression also replaced the requirement for PKC stimulation in activation of the T-cell transcription factor NF-AT. A dominant inhibitory ras mutant specifically blocked antigen receptor agonism, indicating that ras activity is required for antigen receptor signaling. In addition, an inhibitor of PKC blocked both activated ras and phorbol ester stimulation, suggesting a role for ras upstream of PKC. " ], "offsets": [ [ 0, 1008 ] ] } ]

[ { "id": "8428943_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 131, 144 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "7545467__text", "type": "abstract", "text": [ "Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT. \nNuclear factor of activated T cells (NFAT) was originally described as a T-cell-specific transcription factor athat supported the activation of cytokine gene expression and mediated the immunoregulatory effects of cyclosporin A (CsA). As we observed that activated endothelial cells also expressed NFAT, we tested the antiinflammatory properties of CsA in endothelial cells. Significantly, CsA completely suppressed the induction of NFAT in endothelial cells and inhibited the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene regulatory elements that use NFAT by 60%. CsA similarly mediated a reduction of up to 65% in GM-CSF mRNA and protein expression in activated endothelial cells. CsA also suppressed E-selectin, but not vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells, even though the E-selectin promoter is activated by NF-kappa B rather than NFAT. Hence, induction of cell surface expression of this leukocyte adhesion molecule by tumor necrosis factor (TNF)-alpha was reduced by 40% in the presence of CsA, and this was reflected by a 29% decrease in neutrophil adhesion. The effects of CsA on endothelial cells were also detected at the chromatin structure level, as DNasel hypersensitive sites within both the GM-CSF enhancer and the E-selectin promoter were suppressed by CsA. This represents the first report of NFAT in endothelial cells and suggests mechanisms by which CsA could function as an antiinflammatory agent. " ], "offsets": [ [ 0, 1656 ] ] } ]

[ { "id": "7545467_T1", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 14, 62 ] ], "normalized": [] }, { "id": "7545467_T2", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 67, 77 ] ], "normalized": [] }, { "id": "7545467_T3", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 659, 707 ] ], "normalized": [] }, { "id": "7545467_T4", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 709, 715 ] ], "normalized": [] }, { "id": "7545467_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 815, 821 ] ], "normalized": [] }, { "id": "7545467_T6", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 902, 912 ] ], "normalized": [] }, { "id": "7545467_T7", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 922, 955 ] ], "normalized": [] }, { "id": "7545467_T8", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 957, 963 ] ], "normalized": [] }, { "id": "7545467_T9", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1014, 1024 ] ], "normalized": [] }, { "id": "7545467_T10", "type": "Protein", "text": [ "tumor necrosis factor (TNF)-alpha" ], "offsets": [ [ 1162, 1195 ] ], "normalized": [] }, { "id": "7545467_T11", "type": "Protein", "text": [ "DNasel" ], "offsets": [ [ 1400, 1406 ] ], "normalized": [] }, { "id": "7545467_T12", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1444, 1450 ] ], "normalized": [] }, { "id": "7545467_T13", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1468, 1478 ] ], "normalized": [] }, { "id": "7545467_T21", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1025, 1033 ] ], "normalized": [] } ]

[ { "id": "7545467_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E4" } ] }, { "id": "7545467_E2", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E3" } ] }, { "id": "7545467_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 78, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T2" } ] }, { "id": "7545467_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 78, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T1" } ] }, { "id": "7545467_E5", "type": "Negative_regulation", "trigger": { "text": [ "mediated a reduction" ], "offsets": [ [ 778, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E8" } ] }, { "id": "7545467_E6", "type": "Negative_regulation", "trigger": { "text": [ "mediated a reduction" ], "offsets": [ [ 778, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E7" } ] }, { "id": "7545467_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T5" } ] }, { "id": "7545467_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T5" } ] }, { "id": "7545467_E9", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 891, 901 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E12" } ] }, { "id": "7545467_E10", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 891, 901 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E11" } ] }, { "id": "7545467_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 965, 975 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T6" } ] }, { "id": "7545467_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 965, 975 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T8" } ] }, { "id": "7545467_E13", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1037, 1046 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T9" }, { "role": "Site", "ref_id": "7545467_T21" } ] }, { "id": "7545467_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1086, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E15" }, { "role": "Cause", "ref_id": "7545467_T10" } ] }, { "id": "7545467_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1112, 1122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_T9" } ] }, { "id": "7545467_E16", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1200, 1207 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7545467_E14" } ] } ]

[ { "id": "7545467_1", "entity_ids": [ "7545467_T3", "7545467_T4" ] }, { "id": "7545467_2", "entity_ids": [ "7545467_T7", "7545467_T8" ] } ]

[]