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[ { "id": "PMID-10377411__text", "type": "abstract", "text": [ "The intracellular parasite Theileria parva protects infected T cells from apoptosis. \nParasites have evolved a plethora of strategies to ensure their survival. The intracellular parasite Theileria parva secures its propagation and spreads through the infected animal by infecting and transforming T cells, inducing their continuous proliferation and rendering them metastatic. In previous work, we have shown that the parasite induces constitutive activation of the transcription factor NF-kappaB, by inducing the constitutive degradation of its cytoplasmic inhibitors. The biological significance of NF-kappaB activation in T. parva-infected cells, however, has not yet been defined. Cells that have been transformed by viruses or oncogenes can persist only if they manage to avoid destruction by the apoptotic mechanisms that are activated on transformation and that contribute to maintain cellular homeostasis. We now demonstrate that parasite-induced NF-kappaB activation plays a crucial role in the survival of T. parva-transformed T cells by conveying protection against an apoptotic signal that accompanies parasite-mediated transformation. Consequently, inhibition of NF-kappaB nuclear translocation and the expression of dominant negative mutant forms of components of the NF-kappaB activation pathway, such as IkappaBalpha or p65, prompt rapid apoptosis of T. parva-transformed T cells. Our findings offer important insights into parasite survival strategies and demonstrate that parasite-induced constitutive NF-kappaB activation is an essential step in maintaining the transformed phenotype of the infected cells. " ], "offsets": [ [ 0, 1626 ] ] } ]

[ { "id": "PMID-10377411_T1", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1320, 1332 ] ], "normalized": [] }, { "id": "PMID-10377411_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1336, 1339 ] ], "normalized": [] } ]

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[ { "id": "PMID-10378895__text", "type": "abstract", "text": [ "Downregulation of Wilms' tumor gene (WT1) is not a prerequisite for erythroid or megakaryocytic differentiation of the leukemic cell line K562. \nThe Wilms' tumor gene (WT1) encodes a transcription factor of the zinc finger type. A high expression of WT1 has been detected in a range of acute leukemias, and WT1 is downregulated during induced differentiation of some leukemic cell lines. Overexpression of WT1 in some myeloid cell lines confers resistance to differentiation induction. These observations suggest that a high WT1 expression in hematopoietic cells is incompatible with differentiation. In this study, each of the four different isoforms of WT1 was constitutively overexpressed in the leukemic cell line K562. K562 cells express endogenous WT1, which is downregulated as a response to induced differentiation along the erythroid and megakaryocytic pathways. We now demonstrate that a forced exogenous expression of the four different isoforms of WT1 in K562 does not affect the differentiation response, as judged by accumulation of hemoglobin in response to hemin or the expression of megakaryocytic cell surface markers in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). We conclude that downregulation of WT1 during induced differentiation of K562 cells is not a prerequisite for erythroid or megakaryocytic differentiation of these cells. " ], "offsets": [ [ 0, 1365 ] ] } ]

[ { "id": "PMID-10378895_T1", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 37, 40 ] ], "normalized": [] }, { "id": "PMID-10378895_T2", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 168, 171 ] ], "normalized": [] }, { "id": "PMID-10378895_T3", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 250, 253 ] ], "normalized": [] }, { "id": "PMID-10378895_T4", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 307, 310 ] ], "normalized": [] }, { "id": "PMID-10378895_T5", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 406, 409 ] ], "normalized": [] }, { "id": "PMID-10378895_T6", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 525, 528 ] ], "normalized": [] }, { "id": "PMID-10378895_T7", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "PMID-10378895_T8", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 754, 757 ] ], "normalized": [] }, { "id": "PMID-10378895_T9", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 960, 963 ] ], "normalized": [] }, { "id": "PMID-10378895_T10", "type": "Protein", "text": [ "WT1" ], "offsets": [ [ 1230, 1233 ] ], "normalized": [] } ]

[ { "id": "PMID-10378895_E1", "type": "Negative_regulation", "trigger": { "text": [ "Downregulation" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T1" } ] }, { "id": "PMID-10378895_E2", "type": "Positive_regulation", "trigger": { "text": [ "high expression" ], "offsets": [ [ 231, 246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_E3" } ] }, { "id": "PMID-10378895_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 236, 246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T3" } ] }, { "id": "PMID-10378895_E4", "type": "Negative_regulation", "trigger": { "text": [ "downregulated" ], "offsets": [ [ 314, 327 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T4" } ] }, { "id": "PMID-10378895_E5", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 388, 402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T5" } ] }, { "id": "PMID-10378895_E6", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 388, 402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_E5" } ] }, { "id": "PMID-10378895_E7", "type": "Positive_regulation", "trigger": { "text": [ "high" ], "offsets": [ [ 520, 524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_E8" } ] }, { "id": "PMID-10378895_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 529, 539 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T6" } ] }, { "id": "PMID-10378895_E9", "type": "Gene_expression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 678, 691 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T7" } ] }, { "id": "PMID-10378895_E10", "type": "Positive_regulation", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 678, 691 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_E9" } ] }, { "id": "PMID-10378895_E11", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 735, 742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T8" } ] }, { "id": "PMID-10378895_E12", "type": "Negative_regulation", "trigger": { "text": [ "downregulated" ], "offsets": [ [ 768, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_E11" } ] }, { "id": "PMID-10378895_E13", "type": "Positive_regulation", "trigger": { "text": [ "forced" ], "offsets": [ [ 898, 904 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_E14" } ] }, { "id": "PMID-10378895_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 915, 925 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T9" } ] }, { "id": "PMID-10378895_E15", "type": "Negative_regulation", "trigger": { "text": [ "downregulation" ], "offsets": [ [ 1212, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10378895_T10" } ] } ]

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[ { "id": "PMID-10381501__text", "type": "abstract", "text": [ "GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression. \nThe transcription factor GATA-1 is essential for normal erythropoiesis. By examining in vitro-differentiated embryonic stem cells, we showed previously that in the absence of GATA-1, committed erythroid precursors fail to complete maturation and instead undergo apoptosis. The mechanisms by which GATA-1 controls cell survival are unknown. Here we report that in erythroid cells, GATA-1 strongly induces the expression of the anti-apoptotic protein bcl-xL, but not the related proteins bcl-2 and mcl-1. Consistent with a role for bcl-xL in mediating GATA-1-induced erythroid cell survival, in vitro-differentiated bcl-xL-/- embryonic stem cells fail to generate viable mature definitive erythroid cells, a phenotype resembling that of GATA-1 gene disruption. In addition, we show that erythropoietin, which is also required for erythroid cell survival, cooperates with GATA-1 to stimulate bcl-xL gene expression and to maintain erythroid cell viability during terminal maturation. Together, our data show that bcl-xL is essential for normal erythroid development and suggest a regulatory hierarchy in which bcl-xL is a critical downstream effector of GATA-1 and erythropoietin-mediated signals. " ], "offsets": [ [ 0, 1300 ] ] } ]

[ { "id": "PMID-10381501_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "PMID-10381501_T2", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 11, 25 ] ], "normalized": [] }, { "id": "PMID-10381501_T3", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 85, 91 ] ], "normalized": [] }, { "id": "PMID-10381501_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 130, 136 ] ], "normalized": [] }, { "id": "PMID-10381501_T5", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "PMID-10381501_T6", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 402, 408 ] ], "normalized": [] }, { "id": "PMID-10381501_T7", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 485, 491 ] ], "normalized": [] }, { "id": "PMID-10381501_T8", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 554, 560 ] ], "normalized": [] }, { "id": "PMID-10381501_T9", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 591, 596 ] ], "normalized": [] }, { "id": "PMID-10381501_T10", "type": "Protein", "text": [ "mcl-1" ], "offsets": [ [ 601, 606 ] ], "normalized": [] }, { "id": "PMID-10381501_T11", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 635, 641 ] ], "normalized": [] }, { "id": "PMID-10381501_T12", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 655, 661 ] ], "normalized": [] }, { "id": "PMID-10381501_T13", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 719, 725 ] ], "normalized": [] }, { "id": "PMID-10381501_T14", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 840, 846 ] ], "normalized": [] }, { "id": "PMID-10381501_T15", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 890, 904 ] ], "normalized": [] }, { "id": "PMID-10381501_T16", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 974, 980 ] ], "normalized": [] }, { "id": "PMID-10381501_T17", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 994, 1000 ] ], "normalized": [] }, { "id": "PMID-10381501_T18", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 1115, 1121 ] ], "normalized": [] }, { "id": "PMID-10381501_T19", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 1212, 1218 ] ], "normalized": [] }, { "id": "PMID-10381501_T20", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1256, 1262 ] ], "normalized": [] }, { "id": "PMID-10381501_T21", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 1267, 1281 ] ], "normalized": [] } ]

[ { "id": "PMID-10381501_E1", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 74, 84 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E3" }, { "role": "Cause", "ref_id": "PMID-10381501_T1" } ] }, { "id": "PMID-10381501_E2", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 74, 84 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E3" }, { "role": "Cause", "ref_id": "PMID-10381501_T2" } ] }, { "id": "PMID-10381501_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 92, 102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T3" } ] }, { "id": "PMID-10381501_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 501, 508 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E9" }, { "role": "Cause", "ref_id": "PMID-10381501_T7" } ] }, { "id": "PMID-10381501_E5", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 501, 508 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E8" }, { "role": "Cause", "ref_id": "PMID-10381501_T7" } ] }, { "id": "PMID-10381501_E6", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 501, 508 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E7" }, { "role": "Cause", "ref_id": "PMID-10381501_T7" } ] }, { "id": "PMID-10381501_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 513, 523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T9" } ] }, { "id": "PMID-10381501_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 513, 523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T8" } ] }, { "id": "PMID-10381501_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 513, 523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T10" } ] }, { "id": "PMID-10381501_E10", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E12" }, { "role": "Cause", "ref_id": "PMID-10381501_T15" } ] }, { "id": "PMID-10381501_E11", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_E12" }, { "role": "Cause", "ref_id": "PMID-10381501_T16" } ] }, { "id": "PMID-10381501_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1006, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T17" } ] }, { "id": "PMID-10381501_E13", "type": "Regulation", "trigger": { "text": [ "downstream effector" ], "offsets": [ [ 1233, 1252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T19" }, { "role": "Cause", "ref_id": "PMID-10381501_T21" } ] }, { "id": "PMID-10381501_E14", "type": "Regulation", "trigger": { "text": [ "downstream effector" ], "offsets": [ [ 1233, 1252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381501_T19" }, { "role": "Cause", "ref_id": "PMID-10381501_T20" } ] } ]

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[ { "id": "PMID-10381655__text", "type": "abstract", "text": [ "NF-kappaB functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type. \nRecently NF-kappaB has been shown to have both proapoptotic and antiapoptotic functions. In T cell hybridomas, both T cell activators and glucocorticoids induce apoptosis. Here we show that blockade of NF-kappaB activity, using a dominant negative IkappaBalpha, has opposite effects on these two apoptotic signals. Treatment with PMA plus ionomycin (P/I) results in the upregulation of Fas Ligand (FasL) and induction of apoptosis. Inhibition of NF-kappaB activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures, thus establishing NF-kappaB as a proapoptotic factor in this context. Conversely, inhibition of NF-kappaB confers a tenfold increase in glucocorticoid mediated apoptosis, establishing that NF-kappaB also functions as an antiapoptotic factor. We conclude that NF-kappaB is a context-dependent apoptosis regulator. Our data suggests that NF-kappaB may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells. " ], "offsets": [ [ 0, 1150 ] ] } ]

[ { "id": "PMID-10381655_T1", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 355, 367 ] ], "normalized": [] }, { "id": "PMID-10381655_T2", "type": "Protein", "text": [ "Fas Ligand" ], "offsets": [ [ 493, 503 ] ], "normalized": [] }, { "id": "PMID-10381655_T3", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 505, 509 ] ], "normalized": [] }, { "id": "PMID-10381655_T4", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 611, 615 ] ], "normalized": [] } ]

[ { "id": "PMID-10381655_E1", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 477, 489 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381655_T3" } ] }, { "id": "PMID-10381655_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 572, 580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381655_E4" } ] }, { "id": "PMID-10381655_E3", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 589, 597 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381655_E4" } ] }, { "id": "PMID-10381655_E4", "type": "Transcription", "trigger": { "text": [ "induction" ], "offsets": [ [ 598, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10381655_T4" } ] } ]

[ { "id": "PMID-10381655_1", "entity_ids": [ "PMID-10381655_T3", "PMID-10381655_T2" ] } ]

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

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

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

[]

[ { "id": "PMID-10383940__text", "type": "abstract", "text": [ "STAT1 activation during monocyte to macrophage maturation: role of adhesion molecules. \nHuman monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation, closely mimicking their in vivo migration and maturation into extravascular tissues. The mediator(s) of this maturation process has not been yet defined. We investigated the involvement of signal transducers and activators of transcription (STAT) factors in this phenomenon and reported the specific, time-dependent, activation of STAT1 protein starting at day 0/1 of cultivation and maximally expressed at day 5. STAT1 activity was evident on the STAT binding sequences (SBE) present in the promoters of genes which are up-regulated during monocyte to macrophage maturation such as FcgammaRI and ICAM-1, and in the promoter of the transcription factor IFN regulatory factor-1. Moreover, the effect of cell adhesion to fibronectin or laminin was studied to investigate mechanisms involved in STAT1 activation. Compared with monocytes adherent on plastic surfaces, freshly isolated cells allowed to adhere either to fibronectin- or laminin-coated flasks exhibited an increased STAT1 binding activity both in control and in IFN-gamma-treated cells. The molecular events leading to enhanced STAT1 activation and cytokine responsiveness concerned both Y701 and S727 STAT1 phosphorylation. Exogenous addition of transforming growth factor-beta, which exerts an inhibitory effect on some monocytic differentiation markers, inhibited macrophage maturation, integrin expression and STAT1 binding activity. Taken together these results indicate that STAT1 plays a pivotal role in the differentiation/maturation process of monocytes as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes, such as ICAM-1 and FcgammaRI. " ], "offsets": [ [ 0, 1916 ] ] } ]

[ { "id": "PMID-10383940_T1", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10383940_T2", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "PMID-10383940_T3", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 649, 654 ] ], "normalized": [] }, { "id": "PMID-10383940_T4", "type": "Protein", "text": [ "FcgammaRI" ], "offsets": [ [ 818, 827 ] ], "normalized": [] }, { "id": "PMID-10383940_T5", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 832, 838 ] ], "normalized": [] }, { "id": "PMID-10383940_T6", "type": "Protein", "text": [ "IFN regulatory factor-1" ], "offsets": [ [ 888, 911 ] ], "normalized": [] }, { "id": "PMID-10383940_T7", "type": "Protein", "text": [ "fibronectin" ], "offsets": [ [ 954, 965 ] ], "normalized": [] }, { "id": "PMID-10383940_T8", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1027, 1032 ] ], "normalized": [] }, { "id": "PMID-10383940_T9", "type": "Protein", "text": [ "fibronectin" ], "offsets": [ [ 1150, 1161 ] ], "normalized": [] }, { "id": "PMID-10383940_T10", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1211, 1216 ] ], "normalized": [] }, { "id": "PMID-10383940_T11", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1257, 1266 ] ], "normalized": [] }, { "id": "PMID-10383940_T12", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1323, 1328 ] ], "normalized": [] }, { "id": "PMID-10383940_T13", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1397, 1402 ] ], "normalized": [] }, { "id": "PMID-10383940_T14", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1609, 1614 ] ], "normalized": [] }, { "id": "PMID-10383940_T15", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1676, 1681 ] ], "normalized": [] }, { "id": "PMID-10383940_T16", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1894, 1900 ] ], "normalized": [] }, { "id": "PMID-10383940_T17", "type": "Protein", "text": [ "FcgammaRI" ], "offsets": [ [ 1905, 1914 ] ], "normalized": [] }, { "id": "PMID-10383940_T29", "type": "Entity", "text": [ "Y701" ], "offsets": [ [ 1383, 1387 ] ], "normalized": [] }, { "id": "PMID-10383940_T30", "type": "Entity", "text": [ "S727" ], "offsets": [ [ 1392, 1396 ] ], "normalized": [] } ]

[ { "id": "PMID-10383940_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 6, 16 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T1" } ] }, { "id": "PMID-10383940_E2", "type": "Positive_regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 59, 63 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E1" } ] }, { "id": "PMID-10383940_E3", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 552, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T2" } ] }, { "id": "PMID-10383940_E4", "type": "Positive_regulation", "trigger": { "text": [ "maximally expressed" ], "offsets": [ [ 619, 638 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E3" } ] }, { "id": "PMID-10383940_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 688, 695 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T3" } ] }, { "id": "PMID-10383940_E6", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 756, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T5" } ] }, { "id": "PMID-10383940_E7", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 756, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T4" } ] }, { "id": "PMID-10383940_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1033, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T8" } ] }, { "id": "PMID-10383940_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1201, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E10" } ] }, { "id": "PMID-10383940_E10", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1217, 1233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T10" } ] }, { "id": "PMID-10383940_E11", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1314, 1322 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E12" } ] }, { "id": "PMID-10383940_E12", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1329, 1339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T12" } ] }, { "id": "PMID-10383940_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1403, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T13" }, { "role": "Site", "ref_id": "PMID-10383940_T30" } ] }, { "id": "PMID-10383940_E14", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1403, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T13" }, { "role": "Site", "ref_id": "PMID-10383940_T29" } ] }, { "id": "PMID-10383940_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1552, 1561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E16" } ] }, { "id": "PMID-10383940_E16", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1615, 1631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T14" } ] }, { "id": "PMID-10383940_E17", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1801, 1810 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T15" } ] }, { "id": "PMID-10383940_E18", "type": "Regulation", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1841, 1849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E21" }, { "role": "Cause", "ref_id": "PMID-10383940_E17" } ] }, { "id": "PMID-10383940_E19", "type": "Regulation", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1841, 1849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_E20" }, { "role": "Cause", "ref_id": "PMID-10383940_E17" } ] }, { "id": "PMID-10383940_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1854, 1864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T17" } ] }, { "id": "PMID-10383940_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1854, 1864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10383940_T16" } ] } ]

[]

[]

[ { "id": "PMID-10423406__text", "type": "abstract", "text": [ "Stimulation of neutrophil interleukin-8 production by eosinophil granule major basic protein. \nWe evaluated the ability of eosinophil granule major basic protein (MBP) to stimulate interleukin (IL)-8 production by neutrophils. MBP over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml IL-8. Incubation with 2 microM MBP showed that, after a 1 h lag, the level of IL-8 release increased with time for approximately 10 h. At the 2 microM concentration, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase did not stimulate significant levels of IL-8 production. MBP stimulated 2-fold increases in IL-8 messenger RNA (mRNA) after 1 and 3 h of incubation, which were blocked by pretreatment with actinomycin D. However, stimulation with MBP did not produce an increase in the binding activity of nuclear factor (NF)-kappaB or activator protein-1. No NF-IL-6 binding activity was detected in the same nuclear extracts. In addition, stimulation with MBP prolonged the stability of IL-8 mRNA. MBP also induced transient increases in mRNA for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, but did not stimulate the release of either chemokine. These findings indicate that MBP is selective among the eosinophil granule proteins as a stimulus for neutrophil IL-8 release and, further, that stimulation of neutrophil IL-8 release by MBP involves both transcriptional and posttranscriptional regulation. We postulate that MBP-induced release of IL-8 by neutrophils may contribute to the pathophysiology of acute asthma and other inflammatory lung diseases. " ], "offsets": [ [ 0, 1643 ] ] } ]

[ { "id": "PMID-10423406_T1", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 26, 39 ] ], "normalized": [] }, { "id": "PMID-10423406_T2", "type": "Protein", "text": [ "eosinophil granule major basic protein" ], "offsets": [ [ 54, 92 ] ], "normalized": [] }, { "id": "PMID-10423406_T3", "type": "Protein", "text": [ "eosinophil granule major basic protein" ], "offsets": [ [ 123, 161 ] ], "normalized": [] }, { "id": "PMID-10423406_T4", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 163, 166 ] ], "normalized": [] }, { "id": "PMID-10423406_T5", "type": "Protein", "text": [ "interleukin (IL)-8" ], "offsets": [ [ 181, 199 ] ], "normalized": [] }, { "id": "PMID-10423406_T6", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 227, 230 ] ], "normalized": [] }, { "id": "PMID-10423406_T7", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 334, 338 ] ], "normalized": [] }, { "id": "PMID-10423406_T8", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 365, 368 ] ], "normalized": [] }, { "id": "PMID-10423406_T9", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 412, 416 ] ], "normalized": [] }, { "id": "PMID-10423406_T10", "type": "Protein", "text": [ "eosinophil cationic protein" ], "offsets": [ [ 500, 527 ] ], "normalized": [] }, { "id": "PMID-10423406_T11", "type": "Protein", "text": [ "eosinophil peroxidase" ], "offsets": [ [ 564, 585 ] ], "normalized": [] }, { "id": "PMID-10423406_T12", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 626, 630 ] ], "normalized": [] }, { "id": "PMID-10423406_T13", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 643, 646 ] ], "normalized": [] }, { "id": "PMID-10423406_T14", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 678, 682 ] ], "normalized": [] }, { "id": "PMID-10423406_T15", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "PMID-10423406_T16", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "PMID-10423406_T17", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1058, 1062 ] ], "normalized": [] }, { "id": "PMID-10423406_T18", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1069, 1072 ] ], "normalized": [] }, { "id": "PMID-10423406_T19", "type": "Protein", "text": [ "macrophage inflammatory protein (MIP)-1alpha" ], "offsets": [ [ 1118, 1162 ] ], "normalized": [] }, { "id": "PMID-10423406_T20", "type": "Protein", "text": [ "MIP-1beta" ], "offsets": [ [ 1167, 1176 ] ], "normalized": [] }, { "id": "PMID-10423406_T21", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1262, 1265 ] ], "normalized": [] }, { "id": "PMID-10423406_T22", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1346, 1350 ] ], "normalized": [] }, { "id": "PMID-10423406_T23", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1404, 1408 ] ], "normalized": [] }, { "id": "PMID-10423406_T24", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1420, 1423 ] ], "normalized": [] }, { "id": "PMID-10423406_T25", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1508, 1511 ] ], "normalized": [] }, { "id": "PMID-10423406_T26", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1531, 1535 ] ], "normalized": [] } ]

[ { "id": "PMID-10423406_E1", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 40, 50 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T1" } ] }, { "id": "PMID-10423406_E2", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 171, 180 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E3" }, { "role": "Cause", "ref_id": "PMID-10423406_T4" } ] }, { "id": "PMID-10423406_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 200, 210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T5" } ] }, { "id": "PMID-10423406_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 280, 290 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E5" }, { "role": "Cause", "ref_id": "PMID-10423406_T6" } ] }, { "id": "PMID-10423406_E5", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 295, 302 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T7" } ] }, { "id": "PMID-10423406_E6", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 417, 424 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T9" } ] }, { "id": "PMID-10423406_E7", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 425, 434 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E6" }, { "role": "Cause", "ref_id": "PMID-10423406_T8" } ] }, { "id": "PMID-10423406_E8", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 631, 641 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T12" } ] }, { "id": "PMID-10423406_E9", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 647, 657 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E10" }, { "role": "Cause", "ref_id": "PMID-10423406_T13" } ] }, { "id": "PMID-10423406_E10", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 665, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T14" } ] }, { "id": "PMID-10423406_E11", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 746, 753 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E9" } ] }, { "id": "PMID-10423406_E12", "type": "Positive_regulation", "trigger": { "text": [ "prolonged the stability" ], "offsets": [ [ 1031, 1054 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T17" } ] }, { "id": "PMID-10423406_E13", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1096, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T20" }, { "role": "Cause", "ref_id": "PMID-10423406_T18" } ] }, { "id": "PMID-10423406_E14", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1096, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T19" }, { "role": "Cause", "ref_id": "PMID-10423406_T18" } ] }, { "id": "PMID-10423406_E15", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 1190, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E17" }, { "role": "Cause", "ref_id": "PMID-10423406_T18" } ] }, { "id": "PMID-10423406_E16", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 1190, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E18" }, { "role": "Cause", "ref_id": "PMID-10423406_T18" } ] }, { "id": "PMID-10423406_E17", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 1204, 1211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T19" } ] }, { "id": "PMID-10423406_E18", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 1204, 1211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T20" } ] }, { "id": "PMID-10423406_E19", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 1351, 1358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T22" } ] }, { "id": "PMID-10423406_E20", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 1409, 1416 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T23" } ] }, { "id": "PMID-10423406_E21", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1512, 1519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_E22" }, { "role": "Cause", "ref_id": "PMID-10423406_T25" } ] }, { "id": "PMID-10423406_E22", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 1520, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10423406_T26" } ] } ]

[ { "id": "PMID-10423406_1", "entity_ids": [ "PMID-10423406_T4", "PMID-10423406_T3" ] } ]

[]

[ { "id": "PMID-10425206__text", "type": "abstract", "text": [ "PPARgamma activation induces the expression of the adipocyte fatty acid binding protein gene in human monocytes. \nThe peroxisome-proliferator activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily of ligand activated transcription factors, plays a key role in the anti-diabetic actions of the thiazolidinediones (TZDs). PPARgamma induces the expression of many genes involved in lipid anabolism, including the adipocyte fatty acid binding protein (aP2), and is a key regulator of adipocyte differentiation. PPARgamma is also expressed in hematopoietic cells and is up-regulated in activated monocytes/macrophages. Activation of PPARgamma may play a role in the induction of differentiation of macrophages to foam cells that are associated with atherosclerotic lesions. We report that both natural and synthetic PPARgamma agonists induce time- and dose-dependent increases in aP2 mRNA in both primary human monocytes and the monocytic cell line, THP-1. These data suggest that PPARgamma activation may play a role in monocyte differentiation and function analogous to its well-characterized role in adipocytes. " ], "offsets": [ [ 0, 1138 ] ] } ]

[ { "id": "PMID-10425206_T1", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "PMID-10425206_T2", "type": "Protein", "text": [ "adipocyte fatty acid binding protein" ], "offsets": [ [ 51, 87 ] ], "normalized": [] }, { "id": "PMID-10425206_T3", "type": "Protein", "text": [ "peroxisome-proliferator activated receptor gamma" ], "offsets": [ [ 118, 166 ] ], "normalized": [] }, { "id": "PMID-10425206_T4", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 168, 177 ] ], "normalized": [] }, { "id": "PMID-10425206_T5", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 348, 357 ] ], "normalized": [] }, { "id": "PMID-10425206_T6", "type": "Protein", "text": [ "adipocyte fatty acid binding protein" ], "offsets": [ [ 438, 474 ] ], "normalized": [] }, { "id": "PMID-10425206_T7", "type": "Protein", "text": [ "aP2" ], "offsets": [ [ 476, 479 ] ], "normalized": [] }, { "id": "PMID-10425206_T8", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 535, 544 ] ], "normalized": [] }, { "id": "PMID-10425206_T9", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 656, 665 ] ], "normalized": [] }, { "id": "PMID-10425206_T10", "type": "Protein", "text": [ "aP2" ], "offsets": [ [ 903, 906 ] ], "normalized": [] }, { "id": "PMID-10425206_T11", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 1004, 1013 ] ], "normalized": [] } ]

[ { "id": "PMID-10425206_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 10, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T1" } ] }, { "id": "PMID-10425206_E2", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 21, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_E3" }, { "role": "Cause", "ref_id": "PMID-10425206_E1" } ] }, { "id": "PMID-10425206_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 33, 43 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T2" } ] }, { "id": "PMID-10425206_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 358, 365 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_E5" }, { "role": "Cause", "ref_id": "PMID-10425206_T5" } ] }, { "id": "PMID-10425206_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 370, 380 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T7" } ] }, { "id": "PMID-10425206_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 553, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T8" } ] }, { "id": "PMID-10425206_E7", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 593, 605 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T8" } ] }, { "id": "PMID-10425206_E8", "type": "Positive_regulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 642, 652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T9" } ] }, { "id": "PMID-10425206_E9", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 858, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_E10" } ] }, { "id": "PMID-10425206_E10", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 890, 899 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T10" } ] }, { "id": "PMID-10425206_E11", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1014, 1024 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10425206_T11" } ] } ]

[ { "id": "PMID-10425206_1", "entity_ids": [ "PMID-10425206_T3", "PMID-10425206_T4" ] }, { "id": "PMID-10425206_2", "entity_ids": [ "PMID-10425206_T7", "PMID-10425206_T6" ] } ]

[]

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

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

[]

[]

[ { "id": "PMID-10426995__text", "type": "abstract", "text": [ "Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. \nThe generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens. " ], "offsets": [ [ 0, 848 ] ] } ]

[ { "id": "PMID-10426995_T1", "type": "Protein", "text": [ "interleukin-12" ], "offsets": [ [ 192, 206 ] ], "normalized": [] }, { "id": "PMID-10426995_T2", "type": "Protein", "text": [ "IL-12" ], "offsets": [ [ 208, 213 ] ], "normalized": [] }, { "id": "PMID-10426995_T3", "type": "Protein", "text": [ "IL-12" ], "offsets": [ [ 309, 314 ] ], "normalized": [] }, { "id": "PMID-10426995_T4", "type": "Protein", "text": [ "IL-12" ], "offsets": [ [ 469, 474 ] ], "normalized": [] }, { "id": "PMID-10426995_T5", "type": "Protein", "text": [ "nitric oxide synthase" ], "offsets": [ [ 643, 664 ] ], "normalized": [] } ]

[ { "id": "PMID-10426995_E1", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 178, 188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_T2" } ] }, { "id": "PMID-10426995_E2", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 302, 308 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_E3" } ] }, { "id": "PMID-10426995_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 315, 325 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_T3" } ] }, { "id": "PMID-10426995_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 475, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_T4" } ] }, { "id": "PMID-10426995_E5", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 591, 601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_E7" } ] }, { "id": "PMID-10426995_E6", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 606, 615 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_E7" } ] }, { "id": "PMID-10426995_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 616, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_T5" } ] }, { "id": "PMID-10426995_E8", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 633, 642 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426995_T5" } ] } ]

[ { "id": "PMID-10426995_1", "entity_ids": [ "PMID-10426995_T2", "PMID-10426995_T1" ] } ]

[]

[ { "id": "PMID-10426996__text", "type": "abstract", "text": [ "Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. \nApoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor-kappaB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms. " ], "offsets": [ [ 0, 740 ] ] } ]

[ { "id": "PMID-10426996_T1", "type": "Protein", "text": [ "toll-like receptor-2" ], "offsets": [ [ 64, 84 ] ], "normalized": [] }, { "id": "PMID-10426996_T2", "type": "Protein", "text": [ "human Toll-like receptor-2" ], "offsets": [ [ 360, 386 ] ], "normalized": [] }, { "id": "PMID-10426996_T3", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 388, 393 ] ], "normalized": [] }, { "id": "PMID-10426996_T4", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 470, 475 ] ], "normalized": [] }, { "id": "PMID-10426996_T5", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 633, 638 ] ], "normalized": [] }, { "id": "PMID-10426996_T6", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 646, 651 ] ], "normalized": [] } ]

[ { "id": "PMID-10426996_E1", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 453, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426996_E2" } ] }, { "id": "PMID-10426996_E2", "type": "Gene_expression", "trigger": { "text": [ "transfected" ], "offsets": [ [ 453, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10426996_T4" } ] } ]

[ { "id": "PMID-10426996_1", "entity_ids": [ "PMID-10426996_T2", "PMID-10426996_T3" ] } ]

[]

[ { "id": "PMID-10428853__text", "type": "abstract", "text": [ "Tissue-specific regulation of the ecto-5'-nucleotidase promoter. Role of the camp response element site in mediating repression by the upstream regulatory region. \nWe have isolated the 5' region of the ecto-5'-nucleotidase (low K(m) 5'-NT) gene and established that a 969-base pair (bp) fragment confers cell-specific expression of a CAT reporter gene that correlates with the expression of endogenous ecto-5'-NT mRNA and enzymatic activity. A 768-bp upstream negative regulatory region has been identified that conferred lymphocyte-specific negative regulation in a heterologous system with a 244-bp deoxycytidine kinase core promoter. DNase I footprinting identified several protected areas including Sp1, Sp1/AP-2, and cAMP response element (CRE) binding sites within the 201-bp core promoter region and Sp1, NRE-2a, TCF-1/LEF-1, and Sp1/NF-AT binding sites in the upstream regulatory region. Whereas the CRE site was essential in mediating the negative activity of the upstream regulatory region in Jurkat but not in HeLa cells, mutation of the Sp1/AP-2 site decreased promoter activity in both cell lines. Electrophoretic mobility shift assay analysis of proteins binding to the CRE site identified both ATF-1 and ATF-2 in Jurkat cells. Finally, phorbol 12-myristate 13-acetate increased the activity of both the core and the 969-bp promoter fragments, and this increase was abrogated by mutations at the CRE site. In summary, we have identified a tissue-specific regulatory region 5' of the ecto-5'-NT core promoter that requires the presence of a functional CRE site within the basal promoter for its suppressive activity. " ], "offsets": [ [ 0, 1630 ] ] } ]

[ { "id": "PMID-10428853_T1", "type": "Protein", "text": [ "ecto-5'-nucleotidase" ], "offsets": [ [ 34, 54 ] ], "normalized": [] }, { "id": "PMID-10428853_T2", "type": "Protein", "text": [ "ecto-5'-nucleotidase" ], "offsets": [ [ 202, 222 ] ], "normalized": [] }, { "id": "PMID-10428853_T3", "type": "Protein", "text": [ "5'-NT" ], "offsets": [ [ 233, 238 ] ], "normalized": [] }, { "id": "PMID-10428853_T4", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 334, 337 ] ], "normalized": [] }, { "id": "PMID-10428853_T5", "type": "Protein", "text": [ "ecto-5'-NT" ], "offsets": [ [ 402, 412 ] ], "normalized": [] }, { "id": "PMID-10428853_T6", "type": "Protein", "text": [ "DNase I" ], "offsets": [ [ 637, 644 ] ], "normalized": [] }, { "id": "PMID-10428853_T7", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 703, 706 ] ], "normalized": [] }, { "id": "PMID-10428853_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 708, 711 ] ], "normalized": [] }, { "id": "PMID-10428853_T9", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 807, 810 ] ], "normalized": [] }, { "id": "PMID-10428853_T10", "type": "Protein", "text": [ "NRE-2a" ], "offsets": [ [ 812, 818 ] ], "normalized": [] }, { "id": "PMID-10428853_T11", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 820, 825 ] ], "normalized": [] }, { "id": "PMID-10428853_T12", "type": "Protein", "text": [ "LEF-1" ], "offsets": [ [ 826, 831 ] ], "normalized": [] }, { "id": "PMID-10428853_T13", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 837, 840 ] ], "normalized": [] }, { "id": "PMID-10428853_T14", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1049, 1052 ] ], "normalized": [] }, { "id": "PMID-10428853_T15", "type": "Protein", "text": [ "ATF-1" ], "offsets": [ [ 1209, 1214 ] ], "normalized": [] }, { "id": "PMID-10428853_T16", "type": "Protein", "text": [ "ATF-2" ], "offsets": [ [ 1219, 1224 ] ], "normalized": [] }, { "id": "PMID-10428853_T17", "type": "Protein", "text": [ "ecto-5'-NT" ], "offsets": [ [ 1497, 1507 ] ], "normalized": [] }, { "id": "PMID-10428853_T19", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 55, 63 ] ], "normalized": [] } ]

[ { "id": "PMID-10428853_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 16, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_T1" }, { "role": "Site", "ref_id": "PMID-10428853_T19" } ] }, { "id": "PMID-10428853_E2", "type": "Regulation", "trigger": { "text": [ "Role" ], "offsets": [ [ 65, 69 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_E3" } ] }, { "id": "PMID-10428853_E3", "type": "Positive_regulation", "trigger": { "text": [ "mediating" ], "offsets": [ [ 107, 116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_E4" } ] }, { "id": "PMID-10428853_E4", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 117, 127 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_T1" }, { "role": "Site", "ref_id": "PMID-10428853_T19" } ] }, { "id": "PMID-10428853_E5", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 377, 387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_T5" } ] }, { "id": "PMID-10428853_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1169, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_T15" } ] }, { "id": "PMID-10428853_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1169, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10428853_T16" } ] } ]

[ { "id": "PMID-10428853_1", "entity_ids": [ "PMID-10428853_T11", "PMID-10428853_T12" ] } ]

[]

[ { "id": "PMID-10430908__text", "type": "abstract", "text": [ "NF-kappaB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. \nActivation of CD40 is essential for thymus-dependent humoral immune responses and rescuing B cells from apoptosis. Many of the effects of CD40 are believed to be achieved through altered gene expression. In addition to Bcl-x, a known CD40-regulated antiapoptotic molecule, we identified a related antiapoptotic molecule, A1/Bfl-1, as a CD40-inducible gene. Inhibition of the NF-kappaB pathway by overexpression of a dominant-active inhibitor of NF-kappaB abolished CD40-induced up-regulation of both the Bfl-1 and Bcl-x genes and also eliminated the ability of CD40 to rescue Fas-induced cell death. Within the upstream promoter region of Bcl-x, a potential NF-kappaB-binding sequence was found to support NF-kappaB-dependent transcriptional activation. Furthermore, expression of physiological levels of Bcl-x protected B cells from Fas-mediated apoptosis in the absence of NF-kappaB signaling. Thus, our results suggest that CD40-mediated cell survival proceeds through NF-kappaB-dependent up-regulation of Bcl-2 family members. " ], "offsets": [ [ 0, 1145 ] ] } ]

[ { "id": "PMID-10430908_T1", "type": "Protein", "text": [ "Bcl-x" ], "offsets": [ [ 36, 41 ] ], "normalized": [] }, { "id": "PMID-10430908_T2", "type": "Protein", "text": [ "Bfl-1/A1" ], "offsets": [ [ 46, 54 ] ], "normalized": [] }, { "id": "PMID-10430908_T3", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 71, 75 ] ], "normalized": [] }, { "id": "PMID-10430908_T4", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 128, 132 ] ], "normalized": [] }, { "id": "PMID-10430908_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 252, 256 ] ], "normalized": [] }, { "id": "PMID-10430908_T6", "type": "Protein", "text": [ "Bcl-x" ], "offsets": [ [ 333, 338 ] ], "normalized": [] }, { "id": "PMID-10430908_T7", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 348, 352 ] ], "normalized": [] }, { "id": "PMID-10430908_T8", "type": "Protein", "text": [ "A1/Bfl-1" ], "offsets": [ [ 435, 443 ] ], "normalized": [] }, { "id": "PMID-10430908_T9", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 450, 454 ] ], "normalized": [] }, { "id": "PMID-10430908_T10", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 579, 583 ] ], "normalized": [] }, { "id": "PMID-10430908_T11", "type": "Protein", "text": [ "Bfl-1" ], "offsets": [ [ 618, 623 ] ], "normalized": [] }, { "id": "PMID-10430908_T12", "type": "Protein", "text": [ "Bcl-x" ], "offsets": [ [ 628, 633 ] ], "normalized": [] }, { "id": "PMID-10430908_T13", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 675, 679 ] ], "normalized": [] }, { "id": "PMID-10430908_T14", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 690, 693 ] ], "normalized": [] }, { "id": "PMID-10430908_T15", "type": "Protein", "text": [ "Bcl-x" ], "offsets": [ [ 753, 758 ] ], "normalized": [] }, { "id": "PMID-10430908_T16", "type": "Protein", "text": [ "Bcl-x" ], "offsets": [ [ 919, 924 ] ], "normalized": [] }, { "id": "PMID-10430908_T17", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 948, 951 ] ], "normalized": [] }, { "id": "PMID-10430908_T18", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1041, 1045 ] ], "normalized": [] } ]

[ { "id": "PMID-10430908_E1", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 19, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T2" } ] }, { "id": "PMID-10430908_E2", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 19, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T1" } ] }, { "id": "PMID-10430908_E3", "type": "Positive_regulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 114, 124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T4" } ] }, { "id": "PMID-10430908_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 353, 362 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T6" }, { "role": "Cause", "ref_id": "PMID-10430908_T7" } ] }, { "id": "PMID-10430908_E5", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 455, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T8" }, { "role": "Cause", "ref_id": "PMID-10430908_T9" } ] }, { "id": "PMID-10430908_E6", "type": "Negative_regulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 569, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_E9" } ] }, { "id": "PMID-10430908_E7", "type": "Negative_regulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 569, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_E8" } ] }, { "id": "PMID-10430908_E8", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 592, 605 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T11" }, { "role": "Cause", "ref_id": "PMID-10430908_T10" } ] }, { "id": "PMID-10430908_E9", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 592, 605 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T12" }, { "role": "Cause", "ref_id": "PMID-10430908_T10" } ] }, { "id": "PMID-10430908_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 881, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10430908_T16" } ] } ]

[]

[]

[ { "id": "PMID-10430922__text", "type": "abstract", "text": [ "Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. \ncDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors. Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples. By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster, the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined. Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples. Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectively. Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis. These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors. " ], "offsets": [ [ 0, 1390 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-10432288__text", "type": "abstract", "text": [ "Bcl-2-mediated drug resistance: inhibition of apoptosis by blocking nuclear factor of activated T lymphocytes (NFAT)-induced Fas ligand transcription. \nBcl-2 inhibits apoptosis induced by a variety of stimuli, including chemotherapy drugs and glucocorticoids. It is generally accepted that Bcl-2 exerts its antiapoptotic effects mainly by dimerizing with proapoptotic members of the Bcl-2 family such as Bax and Bad. However, the mechanism of the antiapoptotic effects is unclear. Paclitaxel and other drugs that disturb microtubule dynamics kill cells in a Fas/Fas ligand (FasL)-dependent manner; antibody to FasL inhibits paclitaxel-induced apoptosis. We have found that Bcl-2 overexpression leads to the prevention of chemotherapy (paclitaxel)-induced expression of FasL and blocks paclitaxel-induced apoptosis. The mechanism of this effect is that Bcl-2 prevents the nuclear translocation of NFAT (nuclear factor of activated T lymphocytes, a transcription factor activated by microtubule damage) by binding and sequestering calcineurin, a calcium-dependent phosphatase that must dephosphorylate NFAT to move to the nucleus. Without NFAT nuclear translocation, the FasL gene is not transcribed. Thus, it appears that paclitaxel and other drugs that disturb microtubule function kill cells at least in part through the induction of FasL. Furthermore, Bcl-2 antagonizes drug-induced apoptosis by inhibiting calcineurin activation, blocking NFAT nuclear translocation, and preventing FasL expression. The effects of Bcl-2 can be overcome, at least partially, through phosphorylation of Bcl-2. Phosphorylated Bcl-2 cannot bind calcineurin, and NFAT activation, FasL expression, and apoptosis can occur after Bcl-2 phosphorylation. " ], "offsets": [ [ 0, 1731 ] ] } ]

[ { "id": "PMID-10432288_T1", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10432288_T2", "type": "Protein", "text": [ "Fas ligand" ], "offsets": [ [ 125, 135 ] ], "normalized": [] }, { "id": "PMID-10432288_T3", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 152, 157 ] ], "normalized": [] }, { "id": "PMID-10432288_T4", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 290, 295 ] ], "normalized": [] }, { "id": "PMID-10432288_T5", "type": "Protein", "text": [ "Bax" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "PMID-10432288_T6", "type": "Protein", "text": [ "Bad" ], "offsets": [ [ 412, 415 ] ], "normalized": [] }, { "id": "PMID-10432288_T7", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 558, 561 ] ], "normalized": [] }, { "id": "PMID-10432288_T8", "type": "Protein", "text": [ "Fas ligand" ], "offsets": [ [ 562, 572 ] ], "normalized": [] }, { "id": "PMID-10432288_T9", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 574, 578 ] ], "normalized": [] }, { "id": "PMID-10432288_T10", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 610, 614 ] ], "normalized": [] }, { "id": "PMID-10432288_T11", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 673, 678 ] ], "normalized": [] }, { "id": "PMID-10432288_T12", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 769, 773 ] ], "normalized": [] }, { "id": "PMID-10432288_T13", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 852, 857 ] ], "normalized": [] }, { "id": "PMID-10432288_T14", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 1169, 1173 ] ], "normalized": [] }, { "id": "PMID-10432288_T15", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 1335, 1339 ] ], "normalized": [] }, { "id": "PMID-10432288_T16", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1354, 1359 ] ], "normalized": [] }, { "id": "PMID-10432288_T17", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 1485, 1489 ] ], "normalized": [] }, { "id": "PMID-10432288_T18", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1517, 1522 ] ], "normalized": [] }, { "id": "PMID-10432288_T19", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1587, 1592 ] ], "normalized": [] }, { "id": "PMID-10432288_T20", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1609, 1614 ] ], "normalized": [] }, { "id": "PMID-10432288_T21", "type": "Protein", "text": [ "calcineurin" ], "offsets": [ [ 1627, 1638 ] ], "normalized": [] }, { "id": "PMID-10432288_T22", "type": "Protein", "text": [ "FasL" ], "offsets": [ [ 1661, 1665 ] ], "normalized": [] }, { "id": "PMID-10432288_T23", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1708, 1713 ] ], "normalized": [] } ]

[ { "id": "PMID-10432288_E1", "type": "Negative_regulation", "trigger": { "text": [ "blocking" ], "offsets": [ [ 59, 67 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E2" }, { "role": "Cause", "ref_id": "PMID-10432288_T1" } ] }, { "id": "PMID-10432288_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 117, 124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E3" } ] }, { "id": "PMID-10432288_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 136, 149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T2" } ] }, { "id": "PMID-10432288_E4", "type": "Binding", "trigger": { "text": [ "dimerizing" ], "offsets": [ [ 339, 349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T4" }, { "role": "Theme", "ref_id": "PMID-10432288_T5" } ] }, { "id": "PMID-10432288_E5", "type": "Binding", "trigger": { "text": [ "dimerizing" ], "offsets": [ [ 339, 349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T4" }, { "role": "Theme", "ref_id": "PMID-10432288_T6" } ] }, { "id": "PMID-10432288_E6", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 679, 693 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E7" } ] }, { "id": "PMID-10432288_E7", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 679, 693 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T11" } ] }, { "id": "PMID-10432288_E8", "type": "Negative_regulation", "trigger": { "text": [ "leads to the prevention" ], "offsets": [ [ 694, 717 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E9" }, { "role": "Cause", "ref_id": "PMID-10432288_E6" } ] }, { "id": "PMID-10432288_E9", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 747, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E10" } ] }, { "id": "PMID-10432288_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 755, 765 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T12" } ] }, { "id": "PMID-10432288_E11", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1004, 1011 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T13" } ] }, { "id": "PMID-10432288_E12", "type": "Positive_regulation", "trigger": { "text": [ "Without" ], "offsets": [ [ 1129, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E13" } ] }, { "id": "PMID-10432288_E13", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1186, 1197 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T14" } ] }, { "id": "PMID-10432288_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1322, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T15" } ] }, { "id": "PMID-10432288_E15", "type": "Negative_regulation", "trigger": { "text": [ "preventing" ], "offsets": [ [ 1474, 1484 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E16" } ] }, { "id": "PMID-10432288_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1490, 1500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T17" } ] }, { "id": "PMID-10432288_E17", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1568, 1583 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T19" } ] }, { "id": "PMID-10432288_E18", "type": "Phosphorylation", "trigger": { "text": [ "Phosphorylated" ], "offsets": [ [ 1594, 1608 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T20" } ] }, { "id": "PMID-10432288_E19", "type": "Negative_regulation", "trigger": { "text": [ "cannot" ], "offsets": [ [ 1615, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E20" }, { "role": "Cause", "ref_id": "PMID-10432288_E18" } ] }, { "id": "PMID-10432288_E20", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1622, 1626 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T20" }, { "role": "Theme", "ref_id": "PMID-10432288_T21" } ] }, { "id": "PMID-10432288_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1666, 1676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T22" } ] }, { "id": "PMID-10432288_E22", "type": "Positive_regulation", "trigger": { "text": [ "after" ], "offsets": [ [ 1702, 1707 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_E21" }, { "role": "Cause", "ref_id": "PMID-10432288_E23" } ] }, { "id": "PMID-10432288_E23", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1714, 1729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10432288_T23" } ] } ]

[ { "id": "PMID-10432288_1", "entity_ids": [ "PMID-10432288_T8", "PMID-10432288_T9" ] } ]

[]

[ { "id": "PMID-10437913__text", "type": "abstract", "text": [ "Retinoblastoma protein expression leads to reduced Oct-1 DNA binding activity and enhances interleukin-8 expression. \nTumor cell lines with a defective retinoblastoma gene are unable to transcribe the HLA class II genes in response to IFN-gamma treatment, and reconstitution of functional Rb rescues IFN-gamma-induced class II gene expression. However, the molecular mechanism of Rb rescue of the class II genes is unknown. We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA, the prototype class II gene. Oct-1, a POU domain transcription factor, was identified as a repressor of HLA-DRA promoter activity in the Rb-defective cells. Rb expression led to phosphorylation of Oct-1, thus relieving its repressive effect. Oct-1 has also been shown to repress interleukin 8 promoter activity. Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines, interleukin 8 expression is higher in these cell lines. " ], "offsets": [ [ 0, 979 ] ] } ]

[ { "id": "PMID-10437913_T1", "type": "Protein", "text": [ "Retinoblastoma" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "PMID-10437913_T2", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-10437913_T3", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 91, 104 ] ], "normalized": [] }, { "id": "PMID-10437913_T4", "type": "Protein", "text": [ "retinoblastoma" ], "offsets": [ [ 152, 166 ] ], "normalized": [] }, { "id": "PMID-10437913_T5", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 235, 244 ] ], "normalized": [] }, { "id": "PMID-10437913_T6", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 289, 291 ] ], "normalized": [] }, { "id": "PMID-10437913_T7", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 300, 309 ] ], "normalized": [] }, { "id": "PMID-10437913_T8", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 380, 382 ] ], "normalized": [] }, { "id": "PMID-10437913_T9", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 455, 457 ] ], "normalized": [] }, { "id": "PMID-10437913_T10", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 545, 550 ] ], "normalized": [] }, { "id": "PMID-10437913_T11", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 653, 655 ] ], "normalized": [] }, { "id": "PMID-10437913_T12", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 673, 675 ] ], "normalized": [] }, { "id": "PMID-10437913_T13", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 713, 718 ] ], "normalized": [] }, { "id": "PMID-10437913_T14", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 758, 763 ] ], "normalized": [] }, { "id": "PMID-10437913_T15", "type": "Protein", "text": [ "interleukin 8" ], "offsets": [ [ 795, 808 ] ], "normalized": [] }, { "id": "PMID-10437913_T16", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 862, 867 ] ], "normalized": [] }, { "id": "PMID-10437913_T17", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 896, 898 ] ], "normalized": [] }, { "id": "PMID-10437913_T18", "type": "Protein", "text": [ "interleukin 8" ], "offsets": [ [ 923, 936 ] ], "normalized": [] }, { "id": "PMID-10437913_T31", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 809, 817 ] ], "normalized": [] } ]

[ { "id": "PMID-10437913_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 23, 33 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T1" } ] }, { "id": "PMID-10437913_E2", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 43, 50 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_E3" }, { "role": "Cause", "ref_id": "PMID-10437913_E1" } ] }, { "id": "PMID-10437913_E3", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 61, 77 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T2" } ] }, { "id": "PMID-10437913_E4", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 82, 90 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_E5" }, { "role": "Cause", "ref_id": "PMID-10437913_E1" } ] }, { "id": "PMID-10437913_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 105, 115 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T3" } ] }, { "id": "PMID-10437913_E6", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 142, 151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T4" } ] }, { "id": "PMID-10437913_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 458, 468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T9" } ] }, { "id": "PMID-10437913_E8", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 656, 665 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T11" } ] }, { "id": "PMID-10437913_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 676, 686 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T12" } ] }, { "id": "PMID-10437913_E10", "type": "Positive_regulation", "trigger": { "text": [ "led" ], "offsets": [ [ 687, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_E11" }, { "role": "Cause", "ref_id": "PMID-10437913_E9" } ] }, { "id": "PMID-10437913_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 694, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T13" } ] }, { "id": "PMID-10437913_E12", "type": "Negative_regulation", "trigger": { "text": [ "repress" ], "offsets": [ [ 787, 794 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T15" }, { "role": "Cause", "ref_id": "PMID-10437913_T14" }, { "role": "Site", "ref_id": "PMID-10437913_T31" } ] }, { "id": "PMID-10437913_E13", "type": "Negative_regulation", "trigger": { "text": [ "reduced levels" ], "offsets": [ [ 844, 858 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_E14" } ] }, { "id": "PMID-10437913_E14", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 872, 888 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T16" } ] }, { "id": "PMID-10437913_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 937, 947 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_T18" } ] }, { "id": "PMID-10437913_E16", "type": "Positive_regulation", "trigger": { "text": [ "higher" ], "offsets": [ [ 951, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10437913_E15" } ] } ]

[]

[]

[ { "id": "PMID-10438457__text", "type": "abstract", "text": [ "Protein kinase C and calcineurin synergize to activate IkappaB kinase and NF-kappaB in T lymphocytes. \nThe nuclear factor of kappaB (NF-kappaB) is a ubiquitous transcription factor that is key in the regulation of the immune response and inflammation. T cell receptor (TCR) cross-linking is in part required for activation of NF-kappaB, which is dependent on the phosphorylation and degradation of IkappaBalpha. By using Jurkat and primary human T lymphocytes, we demonstrate that the simultaneous activation of two second messengers of the TCR-initiated signal transduction, protein kinase C (PKC) and calcineurin, results in the synergistic activation of the IkappaBalpha kinase (IKK) complex but not of another putative IkappaBalpha kinase, p90(rsk). We also demonstrate that the IKK complex, but not p90(rsk), is responsible for the in vivo phosphorylation of IkappaBalpha mediated by the co-activation of PKC and calcineurin. Each second messenger is necessary, as inhibition of either one reverses the activation of the IKK complex and IkappaBalpha phosphorylation in vivo. Overexpression of dominant negative forms of IKKalpha and -beta demonstrates that only IKKbeta is the target for PKC and calcineurin. These results indicate that within the TCR/CD3 signal transduction pathway both PKC and calcineurin are required for the effective activation of the IKK complex and NF-kappaB in T lymphocytes. " ], "offsets": [ [ 0, 1407 ] ] } ]

[ { "id": "PMID-10438457_T1", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 398, 410 ] ], "normalized": [] }, { "id": "PMID-10438457_T2", "type": "Protein", "text": [ "IkappaBalpha kinase" ], "offsets": [ [ 723, 742 ] ], "normalized": [] }, { "id": "PMID-10438457_T3", "type": "Protein", "text": [ "p90(rsk)" ], "offsets": [ [ 744, 752 ] ], "normalized": [] }, { "id": "PMID-10438457_T4", "type": "Protein", "text": [ "p90(rsk)" ], "offsets": [ [ 804, 812 ] ], "normalized": [] }, { "id": "PMID-10438457_T5", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 864, 876 ] ], "normalized": [] }, { "id": "PMID-10438457_T6", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1042, 1054 ] ], "normalized": [] }, { "id": "PMID-10438457_T7", "type": "Protein", "text": [ "IKKalpha" ], "offsets": [ [ 1125, 1133 ] ], "normalized": [] }, { "id": "PMID-10438457_T8", "type": "Protein", "text": [ "-beta" ], "offsets": [ [ 1138, 1143 ] ], "normalized": [] }, { "id": "PMID-10438457_T9", "type": "Protein", "text": [ "IKKbeta" ], "offsets": [ [ 1167, 1174 ] ], "normalized": [] } ]

[ { "id": "PMID-10438457_E1", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 363, 378 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_T1" } ] }, { "id": "PMID-10438457_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 383, 394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_T1" } ] }, { "id": "PMID-10438457_E3", "type": "Positive_regulation", "trigger": { "text": [ "synergistic activation" ], "offsets": [ [ 631, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_T3" } ] }, { "id": "PMID-10438457_E4", "type": "Regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 817, 828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_E6" }, { "role": "Cause", "ref_id": "PMID-10438457_T4" } ] }, { "id": "PMID-10438457_E5", "type": "Regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 817, 828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_E6" } ] }, { "id": "PMID-10438457_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 845, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_T5" } ] }, { "id": "PMID-10438457_E7", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 877, 885 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_E6" } ] }, { "id": "PMID-10438457_E8", "type": "Negative_regulation", "trigger": { "text": [ "reverses" ], "offsets": [ [ 995, 1003 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_E9" } ] }, { "id": "PMID-10438457_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1055, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_T6" } ] }, { "id": "PMID-10438457_E10", "type": "Regulation", "trigger": { "text": [ "target" ], "offsets": [ [ 1182, 1188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438457_T9" } ] } ]

[]

[]

[ { "id": "PMID-10438731__text", "type": "abstract", "text": [ "C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression. \nEosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPbeta expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site (bp -90 to -82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA- binding sites, we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta. Expression of FOG (riend ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages. " ], "offsets": [ [ 0, 2283 ] ] } ]

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"ref_id": "PMID-10438731_T7" } ] }, { "id": "PMID-10438731_E5", "type": "Negative_regulation", "trigger": { "text": [ "negative regulatory role" ], "offsets": [ [ 390, 414 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_E6" }, { "role": "Cause", "ref_id": "PMID-10438731_T8" } ] }, { "id": "PMID-10438731_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 438, 451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T9" } ] }, { "id": "PMID-10438731_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 802, 812 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T12" } ] }, { "id": "PMID-10438731_E8", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 813, 822 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_E7" } ] }, { "id": "PMID-10438731_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 919, 929 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T13" } ] }, { "id": "PMID-10438731_E10", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 943, 952 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_E9" } ] }, { "id": "PMID-10438731_E11", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1048, 1052 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T14" }, { "role": "Theme", "ref_id": "PMID-10438731_T15" }, { "role": "Site", "ref_id": "PMID-10438731_T46" } ] }, { "id": "PMID-10438731_E12", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1195, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T17" }, { "role": "Theme", "ref_id": "PMID-10438731_T18" }, { "role": "Site", "ref_id": "PMID-10438731_T48" } ] }, { "id": "PMID-10438731_E13", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1195, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T16" }, { "role": "Theme", "ref_id": "PMID-10438731_T18" }, { "role": "Site", "ref_id": "PMID-10438731_T48" } ] }, { "id": "PMID-10438731_E14", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 1393, 1402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T21" }, { "role": "Cause", "ref_id": "PMID-10438731_T20" }, { "role": "Site", "ref_id": "PMID-10438731_T50" } ] }, { "id": "PMID-10438731_E15", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 1393, 1402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T21" }, { "role": "Cause", "ref_id": "PMID-10438731_T19" }, { "role": "Site", "ref_id": "PMID-10438731_T50" } ] }, { "id": "PMID-10438731_E16", "type": "Gene_expression", "trigger": { "text": [ "negative" ], "offsets": [ [ 1448, 1456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T22" } ] }, { "id": "PMID-10438731_E17", "type": 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"PMID-10438731_E22", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1555, 1563 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T21" }, { "role": "Cause", "ref_id": "PMID-10438731_E18" }, { "role": "Site", "ref_id": "PMID-10438731_T50" } ] }, { "id": "PMID-10438731_E23", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1555, 1563 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T21" }, { "role": "Cause", "ref_id": "PMID-10438731_E20" }, { "role": "Site", "ref_id": "PMID-10438731_T50" } ] }, { "id": "PMID-10438731_E24", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1555, 1563 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T21" }, { "role": "Cause", "ref_id": "PMID-10438731_E26" }, { "role": "Site", "ref_id": "PMID-10438731_T50" } ] }, { "id": "PMID-10438731_E25", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], 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"PMID-10438731_E28" } ] }, { "id": "PMID-10438731_E30", "type": "Binding", "trigger": { "text": [ "physical interaction" ], "offsets": [ [ 1709, 1729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T28" }, { "role": "Theme", "ref_id": "PMID-10438731_T29" } ] }, { "id": "PMID-10438731_E31", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1803, 1808 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T30" } ] }, { "id": "PMID-10438731_E32", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1869, 1878 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_E33" } ] }, { "id": "PMID-10438731_E33", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1879, 1894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438731_T32" }, { "role": "Cause", "ref_id": "PMID-10438731_T31" }, { "role": "Site", "ref_id": "PMID-10438731_T61" } ] } ]

[ { "id": "PMID-10438731_1", "entity_ids": [ "PMID-10438731_T6", "PMID-10438731_T5" ] } ]

[]

[ { "id": "PMID-10438843__text", "type": "abstract", "text": [ "Thymocyte-thymic epithelial cell interaction leads to high-level replication of human immunodeficiency virus exclusively in mature CD4(+) CD8(-) CD3(+) thymocytes: a critical role for tumor necrosis factor and interleukin-7. \nThis work aims at identifying the thymocyte subpopulation able to support human immunodeficiency virus (HIV) replication under the biological stimuli of the thymic microenvironment. In this report we demonstrate that interaction with thymic epithelial cells (TEC) induces a high-level replication of the T-tropic primary isolate HIV-1(B-LAIp) exclusively in the mature CD4(+) CD8(-) CD3(+) thymocytes. Tumor necrosis factor (TNF) and interleukin-7 (IL-7), secreted during this interaction, are critical cytokines for HIV long terminal repeat transactivation through NF-kappaB-dependent activation. TNF is the major inducer of NF-kappaB and particularly of the p50-p65 complex, whereas IL-7 acts as a cofactor by sustaining the expression of the p75 TNF receptor. The requirement for TNF is further confirmed by the observation that the inability of the intermediate CD4(+) CD8(-) CD3(-) thymocytes to replicate the virus is associated with a defect in TNF production during their interaction with TEC and correlates with the absence of nuclear NF-kappaB activity in these freshly isolated thymocytes. Addition of exogenous TNF to the intermediate thymocyte cultures induces NF-kappaB activity and is sufficient to promote HIV replication in the cocultures with TEC. The other major subpopulation expressing the CD4 receptor, namely, the double-positive (DP) CD4(+) CD8(+) CD3(+/-) thymocytes, despite the entry of the virus, do not produce a significant level of virus, presumably because they are unresponsive to TNF and IL-7. Together, these data suggest that in vivo, despite an efficient entry of the virus in all the CD4(+) subpopulations, a high viral load may be generated exclusively within the mature CD4(+) CD8(-) CD3(+) subset of thymocytes. However, under conditions of inflammatory response after infection, TNF might also be present in the intermediate thymocyte compartment, leading to efficient HIV replication in these cells. " ], "offsets": [ [ 0, 2169 ] ] } ]

[ { "id": "PMID-10438843_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 131, 134 ] ], "normalized": [] }, { "id": "PMID-10438843_T2", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 184, 205 ] ], "normalized": [] }, { "id": "PMID-10438843_T3", "type": "Protein", "text": [ "interleukin-7" ], "offsets": [ [ 210, 223 ] ], "normalized": [] }, { "id": "PMID-10438843_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 595, 598 ] ], "normalized": [] }, { "id": "PMID-10438843_T5", "type": "Protein", "text": [ "Tumor necrosis factor" ], "offsets": [ [ 628, 649 ] ], "normalized": [] }, { "id": "PMID-10438843_T6", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 651, 654 ] ], "normalized": [] }, { "id": "PMID-10438843_T7", "type": "Protein", "text": [ "interleukin-7" ], "offsets": [ [ 660, 673 ] ], "normalized": [] }, { "id": "PMID-10438843_T8", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 675, 679 ] ], "normalized": [] }, { "id": "PMID-10438843_T9", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 824, 827 ] ], "normalized": [] }, { "id": "PMID-10438843_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 886, 889 ] ], "normalized": [] }, { "id": "PMID-10438843_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 890, 893 ] ], "normalized": [] }, { "id": "PMID-10438843_T12", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 911, 915 ] ], "normalized": [] }, { "id": "PMID-10438843_T13", "type": "Protein", "text": [ "p75 TNF receptor" ], "offsets": [ [ 971, 987 ] ], "normalized": [] }, { "id": "PMID-10438843_T14", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1009, 1012 ] ], "normalized": [] }, { "id": "PMID-10438843_T15", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1092, 1095 ] ], "normalized": [] }, { "id": "PMID-10438843_T16", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1178, 1181 ] ], "normalized": [] }, { "id": "PMID-10438843_T17", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1349, 1352 ] ], "normalized": [] }, { "id": "PMID-10438843_T18", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] }, { "id": "PMID-10438843_T19", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1584, 1587 ] ], "normalized": [] }, { "id": "PMID-10438843_T20", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1740, 1743 ] ], "normalized": [] }, { "id": "PMID-10438843_T21", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1748, 1752 ] ], "normalized": [] }, { "id": "PMID-10438843_T22", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1848, 1851 ] ], "normalized": [] }, { "id": "PMID-10438843_T23", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1936, 1939 ] ], "normalized": [] }, { "id": "PMID-10438843_T24", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 2047, 2050 ] ], "normalized": [] } ]

[ { "id": "PMID-10438843_E1", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 682, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T6" } ] }, { "id": "PMID-10438843_E2", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 682, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T8" } ] }, { "id": "PMID-10438843_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducer" ], "offsets": [ [ 841, 848 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T11" }, { "role": "Cause", "ref_id": "PMID-10438843_T9" } ] }, { "id": "PMID-10438843_E4", "type": "Positive_regulation", "trigger": { "text": [ "inducer" ], "offsets": [ [ 841, 848 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T10" }, { "role": "Cause", "ref_id": "PMID-10438843_T9" } ] }, { "id": "PMID-10438843_E5", "type": "Positive_regulation", "trigger": { "text": [ "acts as a cofactor by sustaining" ], "offsets": [ [ 916, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_E6" }, { "role": "Cause", "ref_id": "PMID-10438843_T12" } ] }, { "id": "PMID-10438843_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 953, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T13" } ] }, { "id": "PMID-10438843_E7", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1182, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T16" } ] }, { "id": "PMID-10438843_E8", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1522, 1532 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T18" } ] }, { "id": "PMID-10438843_E9", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 2065, 2072 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438843_T24" } ] } ]

[ { "id": "PMID-10438843_1", "entity_ids": [ "PMID-10438843_T8", "PMID-10438843_T7" ] }, { "id": "PMID-10438843_2", "entity_ids": [ "PMID-10438843_T6", "PMID-10438843_T5" ] } ]

[]

[ { "id": "PMID-10438913__text", "type": "abstract", "text": [ "IL-2-independent activation and proliferation in human T cells induced by CD28. \nAlthough the role of CD28 in T cell costimulation is firmly established, the mechanisms by which it exerts its costimulatory actions are less clear. In many circumstances it is difficult to distinguish the effects of CD28 from subsequent actions of cytokines, such as IL-2, on T cell proliferation. Here, we report a model of CD28 costimulation using PMA plus the natural ligand CD80 that resulted in very limited stimulation of IL-2, as evidenced by both cytokine production and IL-2 promoter stimulation. Promoter assays revealed CD28-dependent effects on both NF-kappaB and AP-1, but not on NF-AT or the intact IL-2 promoter. In addition, T cell proliferation was completely resistant to the actions of the immunosuppressant cyclosporin A (CsA). Moreover T cell proliferation was unaffected by the addition of blocking Abs to both IL-2 and the IL-2 receptor, demonstrating that this form of costimulation by CD28 was independent of IL-2. We also investigated the effects of stimulating T cell blasts with CD80 alone and found that there was a limited requirement for IL-2 in this system. We conclude that CD28 costimulation can cause substantial T cell proliferation in the absence of IL-2, which is driven by a soluble factor independent of NF-AT transactivation. " ], "offsets": [ [ 0, 1349 ] ] } ]

[ { "id": "PMID-10438913_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10438913_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 74, 78 ] ], "normalized": [] }, { "id": "PMID-10438913_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 102, 106 ] ], "normalized": [] }, { "id": "PMID-10438913_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 298, 302 ] ], "normalized": [] }, { "id": "PMID-10438913_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 349, 353 ] ], "normalized": [] }, { "id": "PMID-10438913_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 407, 411 ] ], "normalized": [] }, { "id": "PMID-10438913_T7", "type": "Protein", "text": [ "CD80" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "PMID-10438913_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 510, 514 ] ], "normalized": [] }, { "id": "PMID-10438913_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 561, 565 ] ], "normalized": [] }, { "id": "PMID-10438913_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 613, 617 ] ], "normalized": [] }, { "id": "PMID-10438913_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 695, 699 ] ], "normalized": [] }, { "id": "PMID-10438913_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 915, 919 ] ], "normalized": [] }, { "id": "PMID-10438913_T13", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 992, 996 ] ], "normalized": [] }, { "id": "PMID-10438913_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1016, 1020 ] ], "normalized": [] }, { "id": "PMID-10438913_T15", "type": "Protein", "text": [ "CD80" ], "offsets": [ [ 1089, 1093 ] ], "normalized": [] }, { "id": "PMID-10438913_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1151, 1155 ] ], "normalized": [] }, { "id": "PMID-10438913_T17", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1189, 1193 ] ], "normalized": [] }, { "id": "PMID-10438913_T18", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1269, 1273 ] ], "normalized": [] }, { "id": "PMID-10438913_T22", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 566, 574 ] ], "normalized": [] }, { "id": "PMID-10438913_T25", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 700, 708 ] ], "normalized": [] } ]

[ { "id": "PMID-10438913_E1", "type": "Negative_regulation", "trigger": { "text": [ "resulted in very limited" ], "offsets": [ [ 470, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438913_E3" } ] }, { "id": "PMID-10438913_E2", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 470, 478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438913_E4" } ] }, { "id": "PMID-10438913_E3", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 495, 506 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438913_T8" } ] }, { "id": "PMID-10438913_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 575, 586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438913_T9" }, { "role": "Site", "ref_id": "PMID-10438913_T22" } ] }, { "id": "PMID-10438913_E5", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 628, 635 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438913_T11" }, { "role": "Cause", "ref_id": "PMID-10438913_T10" }, { "role": "Site", "ref_id": "PMID-10438913_T25" } ] }, { "id": "PMID-10438913_E6", "type": "Negative_regulation", "trigger": { "text": [ "blocking" ], "offsets": [ [ 894, 902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10438913_T12" } ] } ]

[]

[]

[ { "id": "PMID-10440930__text", "type": "abstract", "text": [ "Suppression of TNFalpha-mediated NFkappaB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells. \nFlavonoids are a group of naturally-occurring phenolic compounds in the plant kingdom, and many flavonoids are found with vascular protective properties. Nevertheless how the protective response is exerted by flavonoids is not well characterized. In view of the nuclear factor-kappaB (NFkappaB) may play a central role in the initiation of atherosclerosis, prevention of the activation of NFkappaB represents an important role in protecting vascular injury. In this study, the effects of flavonoids on NFkappaB/inhibitor-kappaB (IkappaB) system in ECV304 cells activated with tumor necrosis factor-alpha (TNFalpha) were examined. We investigated the inhibitory action of six flavonoids on IkappaB kinase (IKK) activity, an enzyme recently found to phosphorylate critical serine residues of IkappaB for degradation. Of six flavonoids tested, myricetin was found to strongly inhibit IKK kinase activity, and prevent the degradation of IkappaBalpha and IkappaBbeta in activated endothelial cells. Furthermore, myricetin was also found to inhibit NFkappaB activity correlated with suppression of monocyte adhesion to ECV304 cells. Therefore we conclude that flavonoids may be of therapeutic value for vascular disease through down regulation of NFkappaB/IkappaB system. Copyright 1999 Wiley-Liss, Inc. " ], "offsets": [ [ 0, 1444 ] ] } ]

[ { "id": "PMID-10440930_T1", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 15, 23 ] ], "normalized": [] }, { "id": "PMID-10440930_T2", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 722, 749 ] ], "normalized": [] }, { "id": "PMID-10440930_T3", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 751, 759 ] ], "normalized": [] }, { "id": "PMID-10440930_T4", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1079, 1091 ] ], "normalized": [] }, { "id": "PMID-10440930_T5", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1096, 1107 ] ], "normalized": [] } ]

[ { "id": "PMID-10440930_E1", "type": "Negative_regulation", "trigger": { "text": [ "prevent" ], "offsets": [ [ 1052, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10440930_E3" } ] }, { "id": "PMID-10440930_E2", "type": "Negative_regulation", "trigger": { "text": [ "prevent" ], "offsets": [ [ 1052, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10440930_E4" } ] }, { "id": "PMID-10440930_E3", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1064, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10440930_T5" } ] }, { "id": "PMID-10440930_E4", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1064, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10440930_T4" } ] } ]

[ { "id": "PMID-10440930_1", "entity_ids": [ "PMID-10440930_T2", "PMID-10440930_T3" ] } ]

[]

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

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

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

[]

[ { "id": "PMID-10452760__text", "type": "abstract", "text": [ "Signal transduction pathways triggered by the FcepsilonRIIb receptor (CD23) in human monocytes lead to nuclear factor-kappaB activation. \nBACKGROUND: Alveolar macrophages play a key role in the initiation of the inflammatory reaction of allergic asthma. Alveolar macrophages and peripheral blood monocytes are activated when IgE/allergen immune complexes bind to the CD23 receptor, which leads to the production of inflammatory cytokines. OBJECTIVE: We sought to investigate the molecular mechanisms regulating this early inflammatory response. We have focused on the study of the signal transduction pathways triggered by CD23 in human monocytes and the promonocytic cell line U937. METHODS: CD23 was cross-linked in human monocytes and U937 cells with IgE immune complexes. Surface expression of CD23 was determined by FACS analysis. Transcription factor activation and gene transcription were studied by gel-shift assays and Northern blot analysis, respectively. IkappaBalpha phosphorylation and degradation was analyzed by Western blot. RESULTS: Nuclear factor (NF)-kappaB is the main transcription factor involved in the gene activation that follows CD23 cross-linking in monocytes. CD23-induced NF-kappaB is a heterodimer composed of p65/p50 subunits. NF-kappaB nuclear translocation is secondary to the phosphorylation and subsequent degradation of the NF-kappaB inhibitory molecule IkappaBalpha. Tyrosine kinase-dependent, and not protein kinase C-dependent, pathways mediate CD23-triggered NF-kappaB activation but do not participate in the direct phosphorylation of IkappaBalpha. IkappaBalpha degradation and NF-kappaB nuclear translocation correlate with transcriptional activation of the inflammatory cytokines TNF-alpha and IL-1beta. CONCLUSIONS: NF-kappaB is the main transcription factor involved in the signal transduction pathway of CD23 in monocytes. " ], "offsets": [ [ 0, 1869 ] ] } ]

[ { "id": "PMID-10452760_T1", "type": "Protein", "text": [ "FcepsilonRIIb receptor" ], "offsets": [ [ 46, 68 ] ], "normalized": [] }, { "id": "PMID-10452760_T2", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 70, 74 ] ], "normalized": [] }, { "id": "PMID-10452760_T3", "type": "Protein", "text": [ "CD23 receptor" ], "offsets": [ [ 367, 380 ] ], "normalized": [] }, { "id": "PMID-10452760_T4", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 623, 627 ] ], "normalized": [] }, { "id": "PMID-10452760_T5", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 693, 697 ] ], "normalized": [] }, { "id": "PMID-10452760_T6", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 798, 802 ] ], "normalized": [] }, { "id": "PMID-10452760_T7", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 966, 978 ] ], "normalized": [] }, { "id": "PMID-10452760_T8", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1155, 1159 ] ], "normalized": [] }, { "id": "PMID-10452760_T9", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1188, 1192 ] ], "normalized": [] }, { "id": "PMID-10452760_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1240, 1243 ] ], "normalized": [] }, { "id": "PMID-10452760_T11", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1244, 1247 ] ], "normalized": [] }, { "id": "PMID-10452760_T12", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1390, 1402 ] ], "normalized": [] }, { "id": "PMID-10452760_T13", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1484, 1488 ] ], "normalized": [] }, { "id": "PMID-10452760_T14", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1576, 1588 ] ], "normalized": [] }, { "id": "PMID-10452760_T15", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1590, 1602 ] ], "normalized": [] }, { "id": "PMID-10452760_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1723, 1732 ] ], "normalized": [] }, { "id": "PMID-10452760_T17", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1737, 1745 ] ], "normalized": [] }, { "id": "PMID-10452760_T18", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1850, 1854 ] ], "normalized": [] } ]

[ { "id": "PMID-10452760_E1", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 355, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T3" } ] }, { "id": "PMID-10452760_E2", "type": "Binding", "trigger": { "text": [ "cross-linked" ], "offsets": [ [ 702, 714 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T5" } ] }, { "id": "PMID-10452760_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 784, 794 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T6" } ] }, { "id": "PMID-10452760_E4", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 979, 994 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T7" } ] }, { "id": "PMID-10452760_E5", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 999, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T7" } ] }, { "id": "PMID-10452760_E6", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 1160, 1173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T8" } ] }, { "id": "PMID-10452760_E7", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1193, 1200 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T10" }, { "role": "Cause", "ref_id": "PMID-10452760_T9" } ] }, { "id": "PMID-10452760_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1193, 1200 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T11" }, { "role": "Cause", "ref_id": "PMID-10452760_T9" } ] }, { "id": "PMID-10452760_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1310, 1325 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T12" } ] }, { "id": "PMID-10452760_E10", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1341, 1352 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T12" } ] }, { "id": "PMID-10452760_E11", "type": "Regulation", "trigger": { "text": [ "participate" ], "offsets": [ [ 1531, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_E12" } ] }, { "id": "PMID-10452760_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1557, 1572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T14" } ] }, { "id": "PMID-10452760_E13", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1603, 1614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T15" } ] }, { "id": "PMID-10452760_E14", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1666, 1692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T16" } ] }, { "id": "PMID-10452760_E15", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1666, 1692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10452760_T17" } ] } ]

[ { "id": "PMID-10452760_1", "entity_ids": [ "PMID-10452760_T1", "PMID-10452760_T2" ] } ]

[]

[ { "id": "PMID-10454636__text", "type": "abstract", "text": [ "Dopamine stimulates expression of the human immunodeficiency virus type 1 via NF-kappaB in cells of the immune system. \nRecent studies have reported that lymphocytes produce, transport and bind dopamine present in plasma. However, the action of dopamine on HIV-1 gene expression in cells of the immune system has not yet been examined. Here, we have investigated the regulation of HIV-1 expression by dopamine in Jurkat T cells and in primary blood mononuclear cells (PBMC). HIV-1 replication was increased by dopamine, which correlated with the increased levels of HIV-1 transactivation. Our transient expression data revealed that dopamine stimulated transcription through the NF-kappaB element present in the long terminal repeat. The importance of NF-kappaB sites was confirmed by using vectors containing wild-type or mutant kappaB sites in a heterologous promoter. Consistent with the role of NF-kappaB in mediating dopamine responsiveness, the proteasome inhibitor MG132 abolished dopamine-induced transcriptional activation. We further explored the effect of dopamine in the presence of phorbol esters or tumor necrosis factor-alpha (TNF-alpha) known to activate NF-kappaB. The combination of dopamine and TNF-alpha led to a stimulation of HIV-1 transcription and replication. However, in contrast with TNF-alpha, dopamine treatment did not affect NF-kappaB DNA binding activity nor the concentrations of p50, p65 and IkappaB-alpha proteins, which suggests a distinct NF-kappaB activation mechanism. These results reveal a new link between the dopamine system, cytokine signaling pathway and regulation of gene expression via the involvement of NF-kappaB in T cells and PBMC. " ], "offsets": [ [ 0, 1684 ] ] } ]

[ { "id": "PMID-10454636_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 1113, 1140 ] ], "normalized": [] }, { "id": "PMID-10454636_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1142, 1151 ] ], "normalized": [] }, { "id": "PMID-10454636_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1214, 1223 ] ], "normalized": [] }, { "id": "PMID-10454636_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1311, 1320 ] ], "normalized": [] }, { "id": "PMID-10454636_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1413, 1416 ] ], "normalized": [] }, { "id": "PMID-10454636_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1418, 1421 ] ], "normalized": [] }, { "id": "PMID-10454636_T7", "type": "Protein", "text": [ "IkappaB-alpha" ], "offsets": [ [ 1426, 1439 ] ], "normalized": [] } ]

[ { "id": "PMID-10454636_E1", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1349, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_E7" }, { "role": "Cause", "ref_id": "PMID-10454636_T4" } ] }, { "id": "PMID-10454636_E2", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1349, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_E9" } ] }, { "id": "PMID-10454636_E3", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1349, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_E9" }, { "role": "Cause", "ref_id": "PMID-10454636_T4" } ] }, { "id": "PMID-10454636_E4", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1349, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_E7" } ] }, { "id": "PMID-10454636_E5", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1349, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_E8" }, { "role": "Cause", "ref_id": "PMID-10454636_T4" } ] }, { "id": "PMID-10454636_E6", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1349, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_E8" } ] }, { "id": "PMID-10454636_E7", "type": "Regulation", "trigger": { "text": [ "concentrations" ], "offsets": [ [ 1395, 1409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_T6" } ] }, { "id": "PMID-10454636_E8", "type": "Regulation", "trigger": { "text": [ "concentrations" ], "offsets": [ [ 1395, 1409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_T7" } ] }, { "id": "PMID-10454636_E9", "type": "Regulation", "trigger": { "text": [ "concentrations" ], "offsets": [ [ 1395, 1409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10454636_T5" } ] } ]

[ { "id": "PMID-10454636_1", "entity_ids": [ "PMID-10454636_T1", "PMID-10454636_T2" ] } ]

[]

[ { "id": "PMID-10455134__text", "type": "abstract", "text": [ "AML1 (CBFalpha2) cooperates with B cell-specific activating protein (BSAP/PAX5) in activation of the B cell-specific BLK gene promoter. \nAML1 plays a critical role during hematopoiesis and chromosomal translocations involving AML1 are commonly associated with different forms of leukemia, including pre-B acute lymphoblastic leukemia. To understand the function of AML1 during B cell differentiation, we analyzed regulatory regions of B cell-specific genes for potential AML1-binding sites and have identified a putative AML1-binding site in the promoter of the B cell-specific tyrosine kinase gene, blk. Gel mobility shift assays and transient transfection assays demonstrate that AML1 binds specifically to this site in the blk promoter and this binding site is important for blk promoter activity. Furthermore, in vitro binding analysis revealed that the AML1 runt DNA-binding domain physically interacts with the paired DNA-binding domain of BSAP, a B cell-specific transcription factor. BSAP has been shown previously to be important for B cell-specific regulation of the blk gene. Physical interaction of AML1 with BSAP correlates with functional cooperativity in transfection studies where AML1 and BSAP synergistically activate blk promoter transcription by more than 50-fold. These results demonstrate physical and functional interactions between AML1 and BSAP and suggest that AML1 is an important factor for regulating a critical B cell-specific gene, blk. " ], "offsets": [ [ 0, 1468 ] ] } ]

[ { "id": "PMID-10455134_T1", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10455134_T2", "type": "Protein", "text": [ "CBFalpha2" ], "offsets": [ [ 6, 15 ] ], "normalized": [] }, { "id": "PMID-10455134_T3", "type": "Protein", "text": [ "B cell-specific activating protein" ], "offsets": [ [ 33, 67 ] ], "normalized": [] }, { "id": "PMID-10455134_T4", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 69, 73 ] ], "normalized": [] }, { "id": "PMID-10455134_T5", "type": "Protein", "text": [ "PAX5" ], "offsets": [ [ 74, 78 ] ], "normalized": [] }, { "id": "PMID-10455134_T6", "type": "Protein", "text": [ "BLK" ], "offsets": [ [ 117, 120 ] ], "normalized": [] }, { "id": "PMID-10455134_T7", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 137, 141 ] ], "normalized": [] }, { "id": "PMID-10455134_T8", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "PMID-10455134_T9", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 365, 369 ] ], "normalized": [] }, { "id": "PMID-10455134_T10", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 471, 475 ] ], "normalized": [] }, { "id": "PMID-10455134_T11", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-10455134_T12", "type": "Protein", "text": [ "B cell-specific tyrosine kinase" ], "offsets": [ [ 562, 593 ] ], "normalized": [] }, { "id": "PMID-10455134_T13", "type": "Protein", "text": [ "blk" ], "offsets": [ [ 600, 603 ] ], "normalized": [] }, { "id": "PMID-10455134_T14", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 682, 686 ] ], "normalized": [] }, { "id": "PMID-10455134_T15", "type": "Protein", "text": [ "blk" ], "offsets": [ [ 726, 729 ] ], "normalized": [] }, { "id": "PMID-10455134_T16", "type": "Protein", "text": [ "blk" ], "offsets": [ [ 778, 781 ] ], "normalized": [] }, { "id": "PMID-10455134_T17", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 858, 862 ] ], "normalized": [] }, { "id": "PMID-10455134_T18", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 946, 950 ] ], "normalized": [] }, { "id": "PMID-10455134_T19", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 992, 996 ] ], "normalized": [] }, { "id": "PMID-10455134_T20", "type": "Protein", "text": [ "blk" ], "offsets": [ [ 1077, 1080 ] ], "normalized": [] }, { "id": "PMID-10455134_T21", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 1111, 1115 ] ], "normalized": [] }, { "id": "PMID-10455134_T22", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 1121, 1125 ] ], "normalized": [] }, { "id": "PMID-10455134_T23", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 1197, 1201 ] ], "normalized": [] }, { "id": "PMID-10455134_T24", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 1206, 1210 ] ], "normalized": [] }, { "id": "PMID-10455134_T25", "type": "Protein", "text": [ "blk" ], "offsets": [ [ 1236, 1239 ] ], "normalized": [] }, { "id": "PMID-10455134_T26", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] }, { "id": "PMID-10455134_T27", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 1365, 1369 ] ], "normalized": [] }, { "id": "PMID-10455134_T28", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 1387, 1391 ] ], "normalized": [] }, { "id": "PMID-10455134_T29", "type": "Protein", "text": [ "blk" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] }, { "id": "PMID-10455134_T31", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 126, 134 ] ], "normalized": [] }, { "id": "PMID-10455134_T34", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 730, 738 ] ], "normalized": [] }, { "id": "PMID-10455134_T36", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 782, 790 ] ], "normalized": [] }, { "id": "PMID-10455134_T38", "type": "Entity", "text": [ "paired DNA-binding domain" ], "offsets": [ [ 917, 942 ] ], "normalized": [] } ]

[ { "id": "PMID-10455134_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 83, 93 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T6" }, { "role": "Cause", "ref_id": "PMID-10455134_T4" }, { "role": "Site", "ref_id": "PMID-10455134_T31" } ] }, { "id": "PMID-10455134_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 83, 93 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T6" }, { "role": "Cause", "ref_id": "PMID-10455134_T1" }, { "role": "Site", "ref_id": "PMID-10455134_T31" } ] }, { "id": "PMID-10455134_E3", "type": "Binding", "trigger": { "text": [ "binding sites" ], "offsets": [ [ 476, 489 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T10" } ] }, { "id": "PMID-10455134_E4", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 687, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T14" }, { "role": "Theme", "ref_id": "PMID-10455134_T15" }, { "role": "Site", "ref_id": "PMID-10455134_T34" } ] }, { "id": "PMID-10455134_E5", "type": "Positive_regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 764, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T16" }, { "role": "Site", "ref_id": "PMID-10455134_T36" } ] }, { "id": "PMID-10455134_E6", "type": "Binding", "trigger": { "text": [ "physically interacts" ], "offsets": [ [ 887, 907 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T18" }, { "role": "Site", "ref_id": "PMID-10455134_T38" } ] }, { "id": "PMID-10455134_E7", "type": "Positive_regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 1029, 1038 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_E8" }, { "role": "Cause", "ref_id": "PMID-10455134_T19" } ] }, { "id": "PMID-10455134_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1059, 1069 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T20" } ] }, { "id": "PMID-10455134_E9", "type": "Binding", "trigger": { "text": [ "Physical interaction" ], "offsets": [ [ 1087, 1107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T21" }, { "role": "Theme", "ref_id": "PMID-10455134_T22" } ] }, { "id": "PMID-10455134_E10", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1227, 1235 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_E12" }, { "role": "Cause", "ref_id": "PMID-10455134_T24" } ] }, { "id": "PMID-10455134_E11", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1227, 1235 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_E12" }, { "role": "Cause", "ref_id": "PMID-10455134_T23" } ] }, { "id": "PMID-10455134_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1249, 1262 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T25" } ] }, { "id": "PMID-10455134_E13", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 1335, 1347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T26" }, { "role": "Theme", "ref_id": "PMID-10455134_T27" } ] }, { "id": "PMID-10455134_E14", "type": "Positive_regulation", "trigger": { "text": [ "important factor" ], "offsets": [ [ 1398, 1414 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_E15" }, { "role": "Cause", "ref_id": "PMID-10455134_T28" } ] }, { "id": "PMID-10455134_E15", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 1419, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10455134_T29" } ] } ]

[ { "id": "PMID-10455134_1", "entity_ids": [ "PMID-10455134_T1", "PMID-10455134_T2" ] }, { "id": "PMID-10455134_2", "entity_ids": [ "PMID-10455134_T4", "PMID-10455134_T3", "PMID-10455134_T5" ] } ]

[]

[ { "id": "PMID-10477683__text", "type": "abstract", "text": [ "c-Maf induces monocytic differentiation and apoptosis in bipotent myeloid progenitors. \nThe transcriptional mechanisms that drive colony-forming unit granulocyte-macrophage (CFU-GM) myeloid progenitors to differentiate into cells of either the granulocytic or monocytic lineage are not fully understood. We have shown that the c-Maf and c-Myb transcription factors physically interact in myeloid cells to form inhibitory complexes that hinder transactivation of c-Myb target genes through direct binding to Myb consensus sites. These complexes arise in a developmentally regulated pattern, peaking at the promyelocyte stage, or in cell model systems, appearing soon after the induction of monocytic differentiation. We wished to determine if this developmentally related interaction is a consequence of myeloid differentiation or an intrinsic differentiating stimulus. Because the elevated Myb:Maf status seen in differentiating cells can be recapitulated by overexpression of c-Maf in myeloid cell lines, we inducibly expressed the c-Maf cDNA in 2 bipotent human myeloid progenitor cells. Elevated levels of c-Maf protein led to marked increases in Myb:Maf complexes and the accumulation of monocyte/macrophage cells, followed by eventual programmed cell death. Analysis of targets that could mediate these phenotypic changes indicated that c-Maf likely plays a key role in myeloid cell development through dual mechanisms; inhibition of a select set of c-Myb regulated targets, such as Bcl-2 and CD13/APN, coupled with the activation of as yet undefined differentiation-promoting genes. " ], "offsets": [ [ 0, 1589 ] ] } ]

[ { "id": "PMID-10477683_T1", "type": "Protein", "text": [ "c-Maf" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10477683_T2", "type": "Protein", "text": [ "c-Maf" ], "offsets": [ [ 327, 332 ] ], "normalized": [] }, { "id": "PMID-10477683_T3", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 337, 342 ] ], "normalized": [] }, { "id": "PMID-10477683_T4", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 462, 467 ] ], "normalized": [] }, { "id": "PMID-10477683_T5", "type": "Protein", "text": [ "c-Maf" ], "offsets": [ [ 977, 982 ] ], "normalized": [] }, { "id": "PMID-10477683_T6", "type": "Protein", "text": [ "c-Maf" ], "offsets": [ [ 1033, 1038 ] ], "normalized": [] }, { "id": "PMID-10477683_T7", "type": "Protein", "text": [ "c-Maf" ], "offsets": [ [ 1109, 1114 ] ], "normalized": [] }, { "id": "PMID-10477683_T8", "type": "Protein", "text": [ "c-Maf" ], "offsets": [ [ 1342, 1347 ] ], "normalized": [] }, { "id": "PMID-10477683_T9", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 1455, 1460 ] ], "normalized": [] }, { "id": "PMID-10477683_T10", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1488, 1493 ] ], "normalized": [] }, { "id": "PMID-10477683_T11", "type": "Protein", "text": [ "CD13" ], "offsets": [ [ 1498, 1502 ] ], "normalized": [] }, { "id": "PMID-10477683_T12", "type": "Protein", "text": [ "APN" ], "offsets": [ [ 1503, 1506 ] ], "normalized": [] } ]

[ { "id": "PMID-10477683_E1", "type": "Binding", "trigger": { "text": [ "physically interact" ], "offsets": [ [ 365, 384 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T2" }, { "role": "Theme", "ref_id": "PMID-10477683_T3" } ] }, { "id": "PMID-10477683_E2", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 959, 973 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_E3" } ] }, { "id": "PMID-10477683_E3", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 959, 973 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T5" } ] }, { "id": "PMID-10477683_E4", "type": "Positive_regulation", "trigger": { "text": [ "Elevated levels" ], "offsets": [ [ 1090, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T7" } ] }, { "id": "PMID-10477683_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1425, 1435 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T11" }, { "role": "Cause", "ref_id": "PMID-10477683_T8" } ] }, { "id": "PMID-10477683_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1425, 1435 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T10" }, { "role": "Cause", "ref_id": "PMID-10477683_T8" } ] }, { "id": "PMID-10477683_E7", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1461, 1470 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T11" }, { "role": "Cause", "ref_id": "PMID-10477683_T9" } ] }, { "id": "PMID-10477683_E8", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1461, 1470 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477683_T10" }, { "role": "Cause", "ref_id": "PMID-10477683_T9" } ] } ]

[ { "id": "PMID-10477683_1", "entity_ids": [ "PMID-10477683_T11", "PMID-10477683_T12" ] } ]

[]

[ { "id": "PMID-10477716__text", "type": "abstract", "text": [ "Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation. \nTumor necrosis factor alpha (TNFalpha) is a pluripotent activator of inflammation by inducing a proinflammatory cytokine cascade. This phenomenon is mediated, in part, through inducible expression of the CXC chemokine, interleukin-8 (IL-8). In this study, we investigate the role of TNFalpha-inducible reactive oxygen species (ROS) in IL-8 expression by \"monocyte-like\" U937 histiocytic lymphoma cells. TNFalpha is a rapid activator of IL-8 gene expression by U937, producing a 50-fold induction of mRNA within 1 hour of treatment. In gene transfection assays, the effect of TNFalpha requires the presence of an inducible nuclear factor-kappaB (NF-kappaB) (Rel A) binding site in the IL-8 promoter. TNFalpha treatment induces a rapid translocation of the 65 kD transcriptional activator NF-kappaB subunit, Rel A, whose binding in the nucleus occurs before changes in intracellular ROS. Pretreatment (or up to 15 minutes posttreatment) relative to TNFalpha with the antioxidant dimethyl sulfoxide (DMSO) (2% [vol/vol]) blocks 80% of NF-kappaB-dependent transcription. Surprisingly, however, DMSO has no effect on inducible Rel A binding. Similar selective effects on NF-kappaB transcription are seen with the unrelated antioxidants, N-acetylcysteine (NAC) and vitamin C. These data indicate that TNFalpha induces a delayed ROS-dependent signalling pathway that is required for NF-kappaB transcriptional activation and is separable from that required for its nuclear translocation. Further definition of this pathway will yield new insights into inflammation initiated by TNFalpha signalling. " ], "offsets": [ [ 0, 1793 ] ] } ]

[ { "id": "PMID-10477716_T1", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 45, 58 ] ], "normalized": [] }, { "id": "PMID-10477716_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 78, 105 ] ], "normalized": [] }, { "id": "PMID-10477716_T3", "type": "Protein", "text": [ "Tumor necrosis factor alpha" ], "offsets": [ [ 202, 229 ] ], "normalized": [] }, { "id": "PMID-10477716_T4", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 231, 239 ] ], "normalized": [] }, { "id": "PMID-10477716_T5", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 421, 434 ] ], "normalized": [] }, { "id": "PMID-10477716_T6", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 436, 440 ] ], "normalized": [] }, { "id": "PMID-10477716_T7", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 485, 493 ] ], "normalized": [] }, { "id": "PMID-10477716_T8", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 537, 541 ] ], "normalized": [] }, { "id": "PMID-10477716_T9", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 605, 613 ] ], "normalized": [] }, { "id": "PMID-10477716_T10", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 638, 642 ] ], "normalized": [] }, { "id": "PMID-10477716_T11", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 777, 785 ] ], "normalized": [] }, { "id": "PMID-10477716_T12", "type": "Protein", "text": [ "Rel A" ], "offsets": [ [ 859, 864 ] ], "normalized": [] }, { "id": "PMID-10477716_T13", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 886, 890 ] ], "normalized": [] }, { "id": "PMID-10477716_T14", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 901, 909 ] ], "normalized": [] }, { "id": "PMID-10477716_T15", "type": "Protein", "text": [ "Rel A" ], "offsets": [ [ 1008, 1013 ] ], "normalized": [] }, { "id": "PMID-10477716_T16", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1149, 1157 ] ], "normalized": [] }, { "id": "PMID-10477716_T17", "type": "Protein", "text": [ "Rel A" ], "offsets": [ [ 1324, 1329 ] ], "normalized": [] }, { "id": "PMID-10477716_T18", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1497, 1505 ] ], "normalized": [] }, { "id": "PMID-10477716_T19", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1772, 1780 ] ], "normalized": [] }, { "id": "PMID-10477716_T25", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 178, 185 ] ], "normalized": [] } ]

[ { "id": "PMID-10477716_E1", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 22, 31 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E2" } ] }, { "id": "PMID-10477716_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 32, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E3" }, { "role": "Cause", "ref_id": "PMID-10477716_T2" } ] }, { "id": "PMID-10477716_E3", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 59, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T1" } ] }, { "id": "PMID-10477716_E4", "type": "Regulation", "trigger": { "text": [ "sensitive" ], "offsets": [ [ 135, 144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E5" } ] }, { "id": "PMID-10477716_E5", "type": "Positive_regulation", "trigger": { "text": [ "activating pathway" ], "offsets": [ [ 145, 163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T1" } ] }, { "id": "PMID-10477716_E6", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 186, 199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T1" }, { "role": "ToLoc", "ref_id": "PMID-10477716_T25" } ] }, { "id": "PMID-10477716_E7", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 378, 387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E8" } ] }, { "id": "PMID-10477716_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 388, 398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T6" } ] }, { "id": "PMID-10477716_E9", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 477, 481 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E10" } ] }, { "id": "PMID-10477716_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 542, 552 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T8" } ] }, { "id": "PMID-10477716_E11", "type": "Positive_regulation", "trigger": { "text": [ "activator" ], "offsets": [ [ 625, 634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E12" }, { "role": "Cause", "ref_id": "PMID-10477716_T9" } ] }, { "id": "PMID-10477716_E12", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 643, 658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T10" } ] }, { "id": "PMID-10477716_E13", "type": "Positive_regulation", "trigger": { "text": [ "producing" ], "offsets": [ [ 668, 677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E14" }, { "role": "Cause", "ref_id": "PMID-10477716_T9" } ] }, { "id": "PMID-10477716_E14", "type": "Transcription", "trigger": { "text": [ "induction" ], "offsets": [ [ 688, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T10" } ] }, { "id": "PMID-10477716_E15", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E16" }, { "role": "Cause", "ref_id": "PMID-10477716_T14" } ] }, { "id": "PMID-10477716_E16", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 936, 949 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T15" } ] }, { "id": "PMID-10477716_E17", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1021, 1028 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T15" } ] }, { "id": "PMID-10477716_E18", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1304, 1310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_E19" } ] }, { "id": "PMID-10477716_E19", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1330, 1337 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10477716_T17" } ] } ]

[ { "id": "PMID-10477716_1", "entity_ids": [ "PMID-10477716_T6", "PMID-10477716_T5" ] }, { "id": "PMID-10477716_2", "entity_ids": [ "PMID-10477716_T3", "PMID-10477716_T4" ] } ]

[]

[ { "id": "PMID-10480426__text", "type": "abstract", "text": [ "Neutrophil maturation and the role of retinoic acid. \nNeutrophil maturation occurs in well defined morphological stages that correlate with the acquisition of molecular markers associated with neutrophil function. A variety of factors are known to play a role in terminal neutrophil maturation, including the vitamin A derivative, retinoic acid. Retinoic acid can directly modulate gene expression via binding to its nuclear receptors, which can, in turn, activate transcription of target genes. A role for retinoic acid during neutrophil maturation has been suggested from a variety of sources. Here we present a review of the mechanism of retinoic acid receptor action and the major evidence showing that normal retinoid signaling is required for neutrophil maturation. " ], "offsets": [ [ 0, 772 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-10482545__text", "type": "abstract", "text": [ "Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax. \nHuman T-cell leukemia virus type 1 (HTLV-1) Tax is thought to play a pivotal role in immortalization of T cells. We have recently shown that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by interleukin-2 (IL-2) deprivation and converted its growth from being IL-2 dependent to being IL-2 independent. In this study, we demonstrate that constitutive expression of bcl-xl but not bcl-2, bcl-xs, bak, bad, or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that expressed Tax. Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax. Similar effects were observed in mutant Tax retaining transactivating ability through NF-kappaB. Deletion or substitution of a putative NF-kappaB binding site identified in the bcl-x promoter significantly decreased Tax-induced transactivation. This NF-kappaB-like element was able to form a complex with NF-kappaB family proteins in vitro. Furthermore, Tax-induced transactivation of the bcl-x promoter was also diminished by the mutant IkappaBalpha, which specifically inhibits NF-kappaB activity. Our findings suggest that constitutive expression of Bcl-x(L) induced by Tax through the NF-kappaB pathway contributes to the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation. " ], "offsets": [ [ 0, 1483 ] ] } ]

[ { "id": "PMID-10482545_T1", "type": "Protein", "text": [ "Bcl-x(L)" ], "offsets": [ [ 13, 21 ] ], "normalized": [] }, { "id": "PMID-10482545_T2", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 71, 74 ] ], "normalized": [] }, { "id": "PMID-10482545_T3", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 142, 145 ] ], "normalized": [] }, { "id": "PMID-10482545_T4", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 192, 195 ] ], "normalized": [] }, { "id": "PMID-10482545_T5", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 307, 310 ] ], "normalized": [] }, { "id": "PMID-10482545_T6", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 379, 392 ] ], "normalized": [] }, { "id": "PMID-10482545_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 394, 398 ] ], "normalized": [] }, { "id": "PMID-10482545_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 448, 452 ] ], "normalized": [] }, { "id": "PMID-10482545_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 472, 476 ] ], "normalized": [] }, { "id": "PMID-10482545_T10", "type": "Protein", "text": [ "bcl-xl" ], "offsets": [ [ 552, 558 ] ], "normalized": [] }, { "id": "PMID-10482545_T11", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 567, 572 ] ], "normalized": [] }, { "id": "PMID-10482545_T12", "type": "Protein", "text": [ "bcl-xs" ], "offsets": [ [ 574, 580 ] ], "normalized": [] }, { "id": "PMID-10482545_T13", "type": "Protein", "text": [ "bak" ], "offsets": [ [ 582, 585 ] ], "normalized": [] }, { "id": "PMID-10482545_T14", "type": "Protein", "text": [ "bad" ], "offsets": [ [ 587, 590 ] ], "normalized": [] }, { "id": "PMID-10482545_T15", "type": "Protein", "text": [ "bax" ], "offsets": [ [ 595, 598 ] ], "normalized": [] }, { "id": "PMID-10482545_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 646, 650 ] ], "normalized": [] }, { "id": "PMID-10482545_T17", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 694, 697 ] ], "normalized": [] }, { "id": "PMID-10482545_T18", "type": "Protein", "text": [ "bcl-x" ], "offsets": [ [ 741, 746 ] ], "normalized": [] }, { "id": "PMID-10482545_T19", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 788, 791 ] ], "normalized": [] }, { "id": "PMID-10482545_T20", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 833, 836 ] ], "normalized": [] }, { "id": "PMID-10482545_T21", "type": "Protein", "text": [ "bcl-x" ], "offsets": [ [ 970, 975 ] ], "normalized": [] }, { "id": "PMID-10482545_T22", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1009, 1012 ] ], "normalized": [] }, { "id": "PMID-10482545_T23", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1147, 1150 ] ], "normalized": [] }, { "id": "PMID-10482545_T24", "type": "Protein", "text": [ "bcl-x" ], "offsets": [ [ 1182, 1187 ] ], "normalized": [] }, { "id": "PMID-10482545_T25", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1231, 1243 ] ], "normalized": [] }, { "id": "PMID-10482545_T26", "type": "Protein", "text": [ "Bcl-x(L)" ], "offsets": [ [ 1346, 1354 ] ], "normalized": [] }, { "id": "PMID-10482545_T27", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1366, 1369 ] ], "normalized": [] }, { "id": "PMID-10482545_T28", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1465, 1469 ] ], "normalized": [] }, { "id": "PMID-10482545_T38", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 747, 755 ] ], "normalized": [] }, { "id": "PMID-10482545_T42", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1188, 1196 ] ], "normalized": [] } ]

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[ { "id": "PMID-10482545_1", "entity_ids": [ "PMID-10482545_T7", "PMID-10482545_T6" ] } ]

[]

[ { "id": "PMID-10485906__text", "type": "abstract", "text": [ "Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression. \nInterferons (IFNs) inhibit induction by IL-4 of multiple genes in human monocytes. However, the mechanism by which IFNs mediate this inhibition has not been defined. IL-4 activates gene expression by inducing tyrosine phosphorylation, homodimerization, and nuclear translocation of the latent transcription factor, STAT6 (signal transducer and activator of transcription-6). STAT6-responsive elements are characteristically present in the promoters of IL-4-inducible genes. Because STAT6 activation is essential for IL-4-induced gene expression, we examined the ability of type I and type II IFNs to regulate activation of STAT6 by IL-4 in primary human monocytes. Pretreatment of monocytes with IFN-beta or IFN-gamma, but not IL-1, IL-2, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, IL-6, or transforming growth factor beta suppressed activation of STAT6 by IL-4. This inhibition was associated with decreased tyrosine phosphorylation and nuclear translocation of STAT6 and was not evident unless the cells were preincubated with IFN for at least 1 hr before IL-4 stimulation. Furthermore, inhibition by IFN could be blocked by cotreatment with actinomycin D and correlated temporally with induction of the JAK/STAT inhibitory gene, SOCS-1. Forced expression of SOCS-1 in a macrophage cell line, RAW264, markedly suppressed trans-activation of an IL-4-inducible reporter as well as IL-6- and IFN-gamma-induced reporter gene activity. These findings demonstrate that IFNs inhibit IL-4-induced activation of STAT6 and STAT6-dependent gene expression, at least in part, by inducing expression of SOCS-1. " ], "offsets": [ [ 0, 1758 ] ] } ]

[ { "id": "PMID-10485906_T1", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 34, 39 ] ], "normalized": [] }, { "id": "PMID-10485906_T2", "type": "Protein", "text": [ "interleukin 4" ], "offsets": [ [ 43, 56 ] ], "normalized": [] }, { "id": "PMID-10485906_T3", "type": "Protein", "text": [ "SOCS-1" ], "offsets": [ [ 88, 94 ] ], "normalized": [] }, { "id": "PMID-10485906_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 153, 157 ] ], "normalized": [] }, { "id": "PMID-10485906_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 279, 283 ] ], "normalized": [] }, { "id": "PMID-10485906_T6", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 428, 433 ] ], "normalized": [] }, { "id": "PMID-10485906_T7", "type": "Protein", "text": [ "signal transducer and activator of transcription-6" ], "offsets": [ [ 435, 485 ] ], "normalized": [] }, { "id": "PMID-10485906_T8", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 488, 493 ] ], "normalized": [] }, { "id": "PMID-10485906_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 565, 569 ] ], "normalized": [] }, { "id": "PMID-10485906_T10", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 595, 600 ] ], "normalized": [] }, { "id": "PMID-10485906_T11", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 629, 633 ] ], "normalized": [] }, { "id": "PMID-10485906_T12", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 736, 741 ] ], "normalized": [] }, { "id": "PMID-10485906_T13", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 745, 749 ] ], "normalized": [] }, { "id": "PMID-10485906_T14", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 809, 817 ] ], "normalized": [] }, { "id": "PMID-10485906_T15", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 821, 830 ] ], "normalized": [] }, { "id": "PMID-10485906_T16", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 840, 844 ] ], "normalized": [] }, { "id": "PMID-10485906_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "PMID-10485906_T18", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "PMID-10485906_T19", "type": "Protein", "text": [ "transforming growth factor beta" ], "offsets": [ [ 949, 980 ] ], "normalized": [] }, { "id": "PMID-10485906_T20", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1006, 1011 ] ], "normalized": [] }, { "id": "PMID-10485906_T21", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "PMID-10485906_T22", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1121, 1126 ] ], "normalized": [] }, { "id": "PMID-10485906_T23", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1216, 1220 ] ], "normalized": [] }, { "id": "PMID-10485906_T24", "type": "Protein", "text": [ "SOCS-1" ], "offsets": [ [ 1390, 1396 ] ], "normalized": [] }, { "id": "PMID-10485906_T25", "type": "Protein", "text": [ "SOCS-1" ], "offsets": [ [ 1419, 1425 ] ], "normalized": [] }, { "id": "PMID-10485906_T26", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "PMID-10485906_T27", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1539, 1543 ] ], "normalized": [] }, { "id": "PMID-10485906_T28", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1549, 1558 ] ], "normalized": [] }, { "id": "PMID-10485906_T29", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1636, 1640 ] ], "normalized": [] }, { "id": "PMID-10485906_T30", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1663, 1668 ] ], "normalized": [] }, { "id": "PMID-10485906_T31", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1673, 1678 ] ], "normalized": [] }, { "id": "PMID-10485906_T32", "type": "Protein", "text": [ "SOCS-1" ], "offsets": [ [ 1750, 1756 ] ], "normalized": [] }, { "id": "PMID-10485906_T38", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 322, 330 ] ], "normalized": [] }, { "id": "PMID-10485906_T41", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 370, 377 ] ], "normalized": [] }, { "id": "PMID-10485906_T49", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1067, 1075 ] ], "normalized": [] }, { "id": "PMID-10485906_T51", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1096, 1103 ] ], "normalized": [] } ]

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321 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E9" }, { "role": "Cause", "ref_id": "PMID-10485906_T5" } ] }, { "id": "PMID-10485906_E6", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 313, 321 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E10" }, { "role": "Cause", "ref_id": "PMID-10485906_T5" } ] }, { "id": "PMID-10485906_E7", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 313, 321 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E8" }, { "role": "Cause", "ref_id": "PMID-10485906_T5" } ] }, { "id": "PMID-10485906_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 331, 346 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T6" }, { "role": "Site", "ref_id": "PMID-10485906_T38" } ] }, { "id": "PMID-10485906_E9", "type": "Binding", "trigger": { "text": [ "homodimerization" ], "offsets": [ [ 348, 364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T6" } ] }, { "id": "PMID-10485906_E10", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 378, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T6" }, { "role": "ToLoc", "ref_id": "PMID-10485906_T41" } ] }, { "id": "PMID-10485906_E11", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 601, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T10" } ] }, { "id": "PMID-10485906_E12", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 713, 721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E13" } ] }, { "id": "PMID-10485906_E13", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 722, 732 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T12" }, { "role": "Cause", "ref_id": "PMID-10485906_T13" } ] }, { "id": "PMID-10485906_E14", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 981, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E20" }, { "role": "Cause", "ref_id": "PMID-10485906_T14" } ] }, { "id": "PMID-10485906_E15", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 981, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E20" }, { "role": "Cause", "ref_id": "PMID-10485906_T16" } ] }, { "id": "PMID-10485906_E16", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 981, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E20" }, { "role": "Cause", "ref_id": "PMID-10485906_T15" } ] }, { "id": "PMID-10485906_E17", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 981, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E20" }, { "role": "Cause", "ref_id": "PMID-10485906_T18" } ] }, { "id": "PMID-10485906_E18", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 981, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E20" }, { "role": "Cause", "ref_id": "PMID-10485906_T19" } ] }, { "id": "PMID-10485906_E19", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 981, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E20" }, { "role": "Cause", "ref_id": "PMID-10485906_T17" } ] }, { "id": "PMID-10485906_E20", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 992, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T20" }, { "role": "Cause", "ref_id": "PMID-10485906_T21" } ] }, { "id": "PMID-10485906_E21", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1057, 1066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E23" } ] }, { "id": "PMID-10485906_E22", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1057, 1066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E24" } ] }, { "id": "PMID-10485906_E23", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1076, 1091 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T22" }, { "role": "Site", "ref_id": "PMID-10485906_T49" } ] }, { "id": "PMID-10485906_E24", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1104, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T22" }, { "role": "ToLoc", "ref_id": "PMID-10485906_T51" } ] }, { "id": "PMID-10485906_E25", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1347, 1356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T24" } ] }, { "id": "PMID-10485906_E26", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1405, 1415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T25" } ] }, { "id": "PMID-10485906_E27", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1628, 1635 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E28" }, { "role": "Cause", "ref_id": "PMID-10485906_E29" } ] }, { "id": "PMID-10485906_E28", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1649, 1659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T30" }, { "role": "Cause", "ref_id": "PMID-10485906_T29" } ] }, { "id": "PMID-10485906_E29", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1727, 1735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_E30" } ] }, { "id": "PMID-10485906_E30", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1736, 1746 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10485906_T32" } ] } ]

[ { "id": "PMID-10485906_1", "entity_ids": [ "PMID-10485906_T6", "PMID-10485906_T7" ] } ]

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[ { "id": "PMID-10487715__text", "type": "abstract", "text": [ "Increased IkappaB expression and diminished nuclear NF-kappaB in human mononuclear cells following hydrocortisone injection. \nWe have recently demonstrated that hydrocortisone and other glucocorticoids inhibit reactive oxygen species (ROS) generation by mononuclear (MNC) and polymorphonuclear leucocytes (PMNL). Since NF-kappaB/IkappaB system regulates the transcription of proinflammatory genes, including those responsible for ROS generation, we tested the hypothesis that hydrocortisone may stimulate IkappaB production thus inhibiting NF-kappaB translocation from the cytosol into the nucleus in MNC, in vivo. One hundred milligram of hydrocortisone was injected intravenously into 4 normal subjects. Blood samples were obtained prior to the injection and at 1, 2, 4, 8 and 24 hr after the injection. Nuclear extracts and total cell lysates were prepared from MNC by standard techniques. IkappaB levels in MNC homogenates increased at 1 hr, peaked at 2-4 hr, started to decrease at 8 hr, and returned to baseline levels at 24 hr. NF-kappaB in MNC nuclear extracts decreased at 1 hr, reached a nadir at 4 hr, gradually increased at 8 hr and returned back to baseline levels at 24 hr. The total protein content of NF-kappaB subunit (P65) in MNC lysates also showed a decrease following hydrocortisone injection. This decrease was observed at 2 hr, reached a nadir at 4 hr, and returned to baseline levels at 24 hr. ROS generation inhibition paralleled NF-kappaB levels in the nucleus. It was inhibited at 1 hr, reached a nadir at 2-4 hr, started to increase at 8 hr, and returned to basal levels at 24 hr. Our data demonstrate that hydrocortisone induces IkappaB and suppresses NF-kappaB expression in MNC in parallel. IkappaB further reduces the translocation of NF-kappaB into the nucleus thus preventing the expression of proinflammatory genes. " ], "offsets": [ [ 0, 1851 ] ] } ]

[ { "id": "PMID-10487715_T1", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 1236, 1239 ] ], "normalized": [] } ]

[ { "id": "PMID-10487715_E1", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1270, 1278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10487715_T1" } ] }, { "id": "PMID-10487715_E2", "type": "Negative_regulation", "trigger": { "text": [ "returned to baseline levels" ], "offsets": [ [ 1380, 1407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10487715_E1" } ] } ]

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[ { "id": "PMID-10491412__text", "type": "abstract", "text": [ "Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells. \nActivation of the transcription factor nuclear factor-kappaB (NFkappaB) is impaired in T cells from patients with renal cell carcinomas (RCCs). In circulating T cells from a subset of patients with RCCs, the suppression of NFkappaB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IkappaBalpha. Tumor-derived soluble products from cultured RCC explants inhibit NFkappaB activity in T cells from healthy volunteers, despite a normal level of stimulus-induced IkappaBalpha degradation in these cells. The inhibitory agent has several features characteristic of a ganglioside, including sensitivity to neuraminidase but not protease treatment; hydrophobicity; and molecular weight less than 3 kDa. Indeed, we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue. Gangliosides prepared from RCC supernatants, as well as the purified bovine gangliosides G(m1) and G(d1a), suppressed NFkappaB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-gamma. Taken together, our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs. " ], "offsets": [ [ 0, 1293 ] ] } ]

[ { "id": "PMID-10491412_T1", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 424, 436 ] ], "normalized": [] }, { "id": "PMID-10491412_T2", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 601, 613 ] ], "normalized": [] }, { "id": "PMID-10491412_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1144, 1148 ] ], "normalized": [] }, { "id": "PMID-10491412_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1153, 1162 ] ], "normalized": [] } ]

[ { "id": "PMID-10491412_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 378, 385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_E2" } ] }, { "id": "PMID-10491412_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 386, 397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_T1" } ] }, { "id": "PMID-10491412_E3", "type": "Negative_regulation", "trigger": { "text": [ "normal level" ], "offsets": [ [ 568, 580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_E5" } ] }, { "id": "PMID-10491412_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 593, 600 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_E5" } ] }, { "id": "PMID-10491412_E5", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 614, 625 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_T2" } ] }, { "id": "PMID-10491412_E6", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1108, 1115 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_E8" } ] }, { "id": "PMID-10491412_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1108, 1115 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_E9" } ] }, { "id": "PMID-10491412_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1116, 1126 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_T4" } ] }, { "id": "PMID-10491412_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1116, 1126 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10491412_T3" } ] } ]

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[ { "id": "PMID-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 ] ] } ]

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

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

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[ { "id": "PMID-1314139__text", "type": "abstract", "text": [ "Transcription factor activation and functional stimulation of human monocytes. \nActivation of expression of genes encoding transcription factors: c-fos and c-jun and formation of AP1 transcriptional complex in human monocytes was investigated. It was found that lipopolysaccharide induced strongly both c-fos and c-jun expression as well as AP1 formation. Interferon gamma activated strongly c-fos and weakly c-jun and AP1. Tumor necrosis factor induced slightly c-fos and had almost no effect on c-jun and AP1. The data suggest that differences in functional responses elicited in monocytes by all three factors may be dependent on different routes on nuclear signalling employed by the factors. " ], "offsets": [ [ 0, 697 ] ] } ]

[ { "id": "PMID-1314139_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 146, 151 ] ], "normalized": [] }, { "id": "PMID-1314139_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 156, 161 ] ], "normalized": [] }, { "id": "PMID-1314139_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 303, 308 ] ], "normalized": [] }, { "id": "PMID-1314139_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 313, 318 ] ], "normalized": [] }, { "id": "PMID-1314139_T5", "type": "Protein", "text": [ "Interferon gamma" ], "offsets": [ [ 356, 372 ] ], "normalized": [] }, { "id": "PMID-1314139_T6", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 392, 397 ] ], "normalized": [] }, { "id": "PMID-1314139_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 409, 414 ] ], "normalized": [] }, { "id": "PMID-1314139_T8", "type": "Protein", "text": [ "Tumor necrosis factor" ], "offsets": [ [ 424, 445 ] ], "normalized": [] }, { "id": "PMID-1314139_T9", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 463, 468 ] ], "normalized": [] }, { "id": "PMID-1314139_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 497, 502 ] ], "normalized": [] } ]

[ { "id": "PMID-1314139_E1", "type": "Positive_regulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 80, 90 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E4" } ] }, { "id": "PMID-1314139_E2", "type": "Positive_regulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 80, 90 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E3" } ] }, { "id": "PMID-1314139_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 94, 104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T1" } ] }, { "id": "PMID-1314139_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 94, 104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T2" } ] }, { "id": "PMID-1314139_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 281, 288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E7" } ] }, { "id": "PMID-1314139_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 281, 288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E8" } ] }, { "id": "PMID-1314139_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 319, 329 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T3" } ] }, { "id": "PMID-1314139_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 319, 329 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T4" } ] }, { "id": "PMID-1314139_E9", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 373, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T7" }, { "role": "Cause", "ref_id": "PMID-1314139_T5" } ] }, { "id": "PMID-1314139_E10", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 373, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T6" }, { "role": "Cause", "ref_id": "PMID-1314139_T5" } ] }, { "id": "PMID-1314139_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 446, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T9" }, { "role": "Cause", "ref_id": "PMID-1314139_T8" } ] }, { "id": "PMID-1314139_E12", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 487, 493 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_T10" }, { "role": "Cause", "ref_id": "PMID-1314139_T8" } ] }, { "id": "PMID-1314139_E13", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E11" } ] }, { "id": "PMID-1314139_E14", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E5" } ] }, { "id": "PMID-1314139_E15", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E9" } ] }, { "id": "PMID-1314139_E16", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E6" } ] }, { "id": "PMID-1314139_E17", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E12" } ] }, { "id": "PMID-1314139_E18", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1314139_E10" } ] } ]

[]

[]

[ { "id": "PMID-1315834__text", "type": "abstract", "text": [ "Interferon-gamma potentiates the antiviral activity and the expression of interferon-stimulated genes induced by interferon-alpha in U937 cells. \nBinding of type I interferon (IFN-alpha/beta) to specific receptors results in the rapid transcriptional activation, independent of protein synthesis, of IFN-alpha-stimulated genes (ISGs) in human fibroblasts and HeLa and Daudi cell lines. The binding of ISGF3 (IFN-stimulated gene factor 3) to the conserved IFN-stimulated response element (ISRE) results in transcriptional activation. This factor is composed of a DNA-binding protein (ISGF3 gamma), which normally is present in the cytoplasm, and other IFN-alpha-activated proteins which preexist as latent cytoplasmic precursors (ISGF3 alpha). We have found that ISG expression in the monocytic U937 cell line differs from most cell lines previously examined. U937 cells express both type I and type II IFN receptors, but only IFN-alpha is capable of inducing antiviral protection in these cells. Pretreatment with IFN-gamma potentiates the IFN-alpha-induced protection, but IFN-gamma alone does not have any antiviral activity. ISG15 mRNA accumulation in U937 cells is not detectable before 6 h of IFN-alpha treatment, peaks at 24 h, and requires protein synthesis. Although IFN-gamma alone does not induce ISG expression, IFN-gamma pretreatment markedly increases and hastens ISG expression and transcriptional induction. Nuclear extracts assayed for the presence of ISRE binding factors by electrophoretic mobility shift assays show that ISGF3 is induced by IFN-alpha within 6 h from undetectable basal levels in untreated U937 cells. Activation of ISGF3 alpha, the latent component of ISGF3, occurs rapidly. However, the increase in ISGF3 activity ultimately correlates with the accumulation of ISGF3 gamma induced by IFN-alpha or IFN-gamma. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1879 ] ] } ]

[ { "id": "PMID-1315834_T1", "type": "Protein", "text": [ "Interferon-gamma" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "PMID-1315834_T2", "type": "Protein", "text": [ "ISGF3 gamma" ], "offsets": [ [ 583, 594 ] ], "normalized": [] }, { "id": "PMID-1315834_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1014, 1023 ] ], "normalized": [] }, { "id": "PMID-1315834_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1074, 1083 ] ], "normalized": [] }, { "id": "PMID-1315834_T5", "type": "Protein", "text": [ "ISG15" ], "offsets": [ [ 1128, 1133 ] ], "normalized": [] }, { "id": "PMID-1315834_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1275, 1284 ] ], "normalized": [] }, { "id": "PMID-1315834_T7", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1323, 1332 ] ], "normalized": [] }, { "id": "PMID-1315834_T8", "type": "Protein", "text": [ "ISGF3 gamma" ], "offsets": [ [ 1798, 1809 ] ], "normalized": [] }, { "id": "PMID-1315834_T9", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1834, 1843 ] ], "normalized": [] }, { "id": "PMID-1315834_T11", "type": "Entity", "text": [ "cytoplasm" ], "offsets": [ [ 630, 639 ] ], "normalized": [] } ]

[ { "id": "PMID-1315834_E1", "type": "Localization", "trigger": { "text": [ "present" ], "offsets": [ [ 615, 622 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1315834_T2" }, { "role": "AtLoc", "ref_id": "PMID-1315834_T11" } ] }, { "id": "PMID-1315834_E2", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1139, 1151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1315834_T5" } ] }, { "id": "PMID-1315834_E3", "type": "Positive_regulation", "trigger": { "text": [ "detectable" ], "offsets": [ [ 1173, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1315834_E2" } ] }, { "id": "PMID-1315834_E4", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 1238, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1315834_E3" } ] }, { "id": "PMID-1315834_E5", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1782, 1794 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1315834_T8" } ] }, { "id": "PMID-1315834_E6", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1782, 1794 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1315834_T8" }, { "role": "Cause", "ref_id": "PMID-1315834_T9" } ] } ]

[]

[]

[ { "id": "PMID-1372388__text", "type": "abstract", "text": [ "A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 kappa B-related motifs whose activities are repressed in lymphoid cells. \nThe proto-oncoprotein c-Rel is a member of the nuclear factor kappa B transcription factor family, which includes the p50 and p65 subunits of nuclear factor kappa B. We show here that c-Rel binds to kappa B sites as homodimers as well as heterodimers with p50. These homodimers and heterodimers show distinct DNA-binding specificities and affinities for various kappa B motifs. In particular, the c-Rel homodimer has a high affinity for interleukin-6 (IL-6) and beta interferon kappa B sites. In spite of its association with p50 in vitro, however, we found a lymphoid cell-specific nuclear factor in vivo that contains c-Rel but not p50 epitopes; this factor, termed IL-6 kappa B binding factor II, appears to contain the c-Rel homodimer and preferentially recognizes several IL-6 kappa B-related kappa B motifs. Although it has been previously shown that the IL-6 kappa B motif functions as a potent IL-1/tumor necrosis factor-responsive element in nonlymphoid cells, its activity was found to be repressed in lymphoid cells such as a Jurkat T-cell line. We also present evidence that IL-6 kappa B binding factor II functions as a repressor specific for IL-6 kappa B-related kappa B motifs in lymphoid cells. " ], "offsets": [ [ 0, 1400 ] ] } ]

[ { "id": "PMID-1372388_T1", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-1372388_T2", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 101, 114 ] ], "normalized": [] }, { "id": "PMID-1372388_T3", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 211, 216 ] ], "normalized": [] }, { "id": "PMID-1372388_T4", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 373, 378 ] ], "normalized": [] }, { "id": "PMID-1372388_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 445, 448 ] ], "normalized": [] }, { "id": "PMID-1372388_T6", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 586, 591 ] ], "normalized": [] }, { "id": "PMID-1372388_T7", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 626, 639 ] ], "normalized": [] }, { "id": "PMID-1372388_T8", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 641, 645 ] ], "normalized": [] }, { "id": "PMID-1372388_T9", "type": "Protein", "text": [ "beta interferon" ], "offsets": [ [ 651, 666 ] ], "normalized": [] }, { "id": "PMID-1372388_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "PMID-1372388_T11", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 809, 814 ] ], "normalized": [] }, { "id": "PMID-1372388_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 823, 826 ] ], "normalized": [] }, { "id": "PMID-1372388_T13", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 857, 861 ] ], "normalized": [] }, { "id": "PMID-1372388_T14", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 912, 917 ] ], "normalized": [] }, { "id": "PMID-1372388_T15", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 966, 970 ] ], "normalized": [] }, { "id": "PMID-1372388_T16", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1050, 1054 ] ], "normalized": [] }, { "id": "PMID-1372388_T17", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 1096, 1117 ] ], "normalized": [] }, { "id": "PMID-1372388_T18", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1276, 1280 ] ], "normalized": [] }, { "id": "PMID-1372388_T19", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1345, 1349 ] ], "normalized": [] }, { "id": "PMID-1372388_T26", "type": "Entity", "text": [ "kappa B sites" ], "offsets": [ [ 667, 680 ] ], "normalized": [] } ]

[ { "id": "PMID-1372388_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 379, 384 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T4" } ] }, { "id": "PMID-1372388_E2", "type": "Binding", "trigger": { "text": [ "homodimers" ], "offsets": [ [ 405, 415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T4" } ] }, { "id": "PMID-1372388_E3", "type": "Binding", "trigger": { "text": [ "heterodimers" ], "offsets": [ [ 427, 439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T4" }, { "role": "Theme", "ref_id": "PMID-1372388_T5" } ] }, { "id": "PMID-1372388_E4", "type": "Binding", "trigger": { "text": [ "binding specificities" ], "offsets": [ [ 502, 523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T4" } ] }, { "id": "PMID-1372388_E5", "type": "Binding", "trigger": { "text": [ "affinities" ], "offsets": [ [ 528, 538 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T4" } ] }, { "id": "PMID-1372388_E6", "type": "Binding", "trigger": { "text": [ "high affinity" ], "offsets": [ [ 608, 621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T6" }, { "role": "Theme", "ref_id": "PMID-1372388_T9" }, { "role": "Site", "ref_id": "PMID-1372388_T26" } ] }, { "id": "PMID-1372388_E7", "type": "Binding", "trigger": { "text": [ "high affinity" ], "offsets": [ [ 608, 621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T6" }, { "role": "Theme", "ref_id": "PMID-1372388_T8" }, { "role": "Site", "ref_id": "PMID-1372388_T26" } ] }, { "id": "PMID-1372388_E8", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 698, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T10" }, { "role": "Theme", "ref_id": "PMID-1372388_T13" } ] }, { "id": "PMID-1372388_E9", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 698, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T10" } ] }, { "id": "PMID-1372388_E10", "type": "Binding", "trigger": { "text": [ "recognizes" ], "offsets": [ [ 947, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1372388_T13" } ] } ]

[ { "id": "PMID-1372388_1", "entity_ids": [ "PMID-1372388_T8", "PMID-1372388_T7" ] } ]

[]

[ { "id": "PMID-1375324__text", "type": "abstract", "text": [ "The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. \nThe CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene. " ], "offsets": [ [ 0, 1380 ] ] } ]

[ { "id": "PMID-1375324_T1", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 20, 24 ] ], "normalized": [] }, { "id": "PMID-1375324_T2", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 87, 91 ] ], "normalized": [] }, { "id": "PMID-1375324_T3", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 98, 102 ] ], "normalized": [] }, { "id": "PMID-1375324_T4", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 413, 417 ] ], "normalized": [] }, { "id": "PMID-1375324_T5", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 468, 472 ] ], "normalized": [] }, { "id": "PMID-1375324_T6", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 526, 530 ] ], "normalized": [] }, { "id": "PMID-1375324_T7", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 565, 569 ] ], "normalized": [] }, { "id": "PMID-1375324_T8", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 673, 677 ] ], "normalized": [] }, { "id": "PMID-1375324_T9", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 857, 861 ] ], "normalized": [] }, { "id": "PMID-1375324_T10", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 875, 879 ] ], "normalized": [] }, { "id": "PMID-1375324_T11", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 1020, 1024 ] ], "normalized": [] }, { "id": "PMID-1375324_T12", "type": "Protein", "text": [ "beta-globin reporter" ], "offsets": [ [ 1091, 1111 ] ], "normalized": [] }, { "id": "PMID-1375324_T13", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 1169, 1173 ] ], "normalized": [] }, { "id": "PMID-1375324_T14", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 1280, 1284 ] ], "normalized": [] }, { "id": "PMID-1375324_T15", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 1339, 1343 ] ], "normalized": [] }, { "id": "PMID-1375324_T16", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 1369, 1373 ] ], "normalized": [] }, { "id": "PMID-1375324_T17", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 4, 12 ] ], "normalized": [] }, { "id": "PMID-1375324_T24", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1285, 1293 ] ], "normalized": [] } ]

[ { "id": "PMID-1375324_E1", "type": "Binding", "trigger": { "text": [ "target" ], "offsets": [ [ 35, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T1" }, { "role": "Theme", "ref_id": "PMID-1375324_T2" }, { "role": "Site", "ref_id": "PMID-1375324_T17" } ] }, { "id": "PMID-1375324_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 114, 123 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T3" } ] }, { "id": "PMID-1375324_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 387, 397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T4" } ] }, { "id": "PMID-1375324_E4", "type": "Binding", "trigger": { "text": [ "occupied" ], "offsets": [ [ 845, 853 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T9" } ] }, { "id": "PMID-1375324_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1212, 1219 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T13" } ] }, { "id": "PMID-1375324_E6", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1261, 1270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T13" }, { "role": "Theme", "ref_id": "PMID-1375324_T14" }, { "role": "Site", "ref_id": "PMID-1375324_T24" } ] }, { "id": "PMID-1375324_E7", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1351, 1361 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375324_T16" }, { "role": "Cause", "ref_id": "PMID-1375324_T15" } ] } ]

[]

[]

[ { "id": "PMID-1380242__text", "type": "abstract", "text": [ "SRC-related proto-oncogenes and transcription factors in primary human T cells: modulation by cyclosporin A and FK506. \nActivation of T lymphocytes induces transcription of genes encoding for lymphokines. Interleukin-2 (IL-2) gene expression is controlled transcriptionally by the cooperative activity of specific trans-activating factors that bind to the IL-2 enhancer. Cyclosporin A (CsA) and FK506 inhibit the production of IL-2 in T lymphocytes at the level of gene transcription. A member of the src gene family, the lymphocyte-specific protein tyrosine kinase, p56lck, has been implicated in IL-2 production. CsA was found not to inhibit lck gene expression, nor the activity of the lck gene product. However, CsA and FK506 inhibit the appearance of DNA binding activity of factors that bind to the NF-AT and AP-1 sites in the IL-2 enhancer. Since the induction of NF-AT and AP-1 is induced by the same stimuli that stimulate IL-2 production, these results indicate that the immunosuppressant action of CsA and FK506 is exerted at the level of these trans-activating factors. " ], "offsets": [ [ 0, 1082 ] ] } ]

[ { "id": "PMID-1380242_T1", "type": "Protein", "text": [ "Interleukin-2" ], "offsets": [ [ 205, 218 ] ], "normalized": [] }, { "id": "PMID-1380242_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 220, 224 ] ], "normalized": [] }, { "id": "PMID-1380242_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 356, 360 ] ], "normalized": [] }, { "id": "PMID-1380242_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 427, 431 ] ], "normalized": [] }, { "id": "PMID-1380242_T5", "type": "Protein", "text": [ "p56lck" ], "offsets": [ [ 567, 573 ] ], "normalized": [] }, { "id": "PMID-1380242_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 598, 602 ] ], "normalized": [] }, { "id": "PMID-1380242_T7", "type": "Protein", "text": [ "lck" ], "offsets": [ [ 644, 647 ] ], "normalized": [] }, { "id": "PMID-1380242_T8", "type": "Protein", "text": [ "lck" ], "offsets": [ [ 689, 692 ] ], "normalized": [] }, { "id": "PMID-1380242_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 833, 837 ] ], "normalized": [] }, { "id": "PMID-1380242_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 932, 936 ] ], "normalized": [] }, { "id": "PMID-1380242_T14", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 361, 369 ] ], "normalized": [] } ]

[ { "id": "PMID-1380242_E1", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 245, 255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_E2" } ] }, { "id": "PMID-1380242_E2", "type": "Transcription", "trigger": { "text": [ "transcriptionally" ], "offsets": [ [ 256, 273 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T2" } ] }, { "id": "PMID-1380242_E3", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 344, 348 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T3" }, { "role": "Site", "ref_id": "PMID-1380242_T14" } ] }, { "id": "PMID-1380242_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 401, 408 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_E5" } ] }, { "id": "PMID-1380242_E5", "type": "Transcription", "trigger": { "text": [ "gene transcription" ], "offsets": [ [ 465, 483 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T4" } ] }, { "id": "PMID-1380242_E6", "type": "Regulation", "trigger": { "text": [ "implicated" ], "offsets": [ [ 584, 594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_E7" }, { "role": "Cause", "ref_id": "PMID-1380242_T5" } ] }, { "id": "PMID-1380242_E7", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 603, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T6" } ] }, { "id": "PMID-1380242_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 636, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T7" } ] }, { "id": "PMID-1380242_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 636, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_E10" } ] }, { "id": "PMID-1380242_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 653, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T7" } ] }, { "id": "PMID-1380242_E11", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 922, 931 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_E12" } ] }, { "id": "PMID-1380242_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 937, 947 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1380242_T10" } ] } ]

[ { "id": "PMID-1380242_1", "entity_ids": [ "PMID-1380242_T2", "PMID-1380242_T1" ] } ]

[]

[ { "id": "PMID-1386962__text", "type": "abstract", "text": [ "The development of functionally responsive T cells. \nThe work reviewed in this article separates T cell development into four phases. First is an expansion phase prior to TCR rearrangement, which appears to be correlated with programming of at least some response genes for inducibility. This phase can occur to some extent outside of the thymus. However, the profound T cell deficit of nude mice indicates that the thymus is by far the most potent site for inducing the expansion per se, even if other sites can induce some response acquisition. Second is a controlled phase of TCR gene rearrangement. The details of the regulatory mechanism that selects particular loci for rearrangement are still not known. It seems that the rearrangement of the TCR gamma loci in the gamma delta lineage may not always take place at a developmental stage strictly equivalent to the rearrangement of TCR beta in the alpha beta lineage, and it is not clear just how early the two lineages diverge. In the TCR alpha beta lineage, however, the final gene rearrangement events are accompanied by rapid proliferation and an interruption in cellular response gene inducibility. The loss of conventional responsiveness is probably caused by alterations at the level of signaling, and may be a manifestation of the physiological state that is a precondition for selection. Third is the complex process of selection. Whereas peripheral T cells can undergo forms of positive selection (by antigen-driven clonal expansion) and negative selection (by abortive stimulation leading to anergy or death), neither is exactly the same phenomenon that occurs in the thymic cortex. Negative selection in the cortex appears to be a suicidal inversion of antigen responsiveness: instead of turning on IL-2 expression, the activated cell destroys its own chromatin. The genes that need to be induced for this response are not yet identified, but it is unquestionably a form of activation. It is interesting that in humans and rats, cortical thymocytes undergoing negative selection can still induce IL-2R alpha expression and even be rescued in vitro, if exogenous IL-2 is provided. Perhaps murine thymocytes are denied this form of rescue because they shut off IL-2R beta chain expression at an earlier stage or because they may be uncommonly Bcl-2 deficient (cf. Sentman et al., 1991; Strasser et al., 1991). Even so, medullary thymocytes remain at least partially susceptible to negative selection even as they continue to mature . " ], "offsets": [ [ 0, 2499 ] ] } ]

[ { "id": "PMID-1386962_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1766, 1770 ] ], "normalized": [] }, { "id": "PMID-1386962_T2", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 2063, 2074 ] ], "normalized": [] }, { "id": "PMID-1386962_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 2129, 2133 ] ], "normalized": [] }, { "id": "PMID-1386962_T4", "type": "Protein", "text": [ "IL-2R beta chain" ], "offsets": [ [ 2226, 2242 ] ], "normalized": [] }, { "id": "PMID-1386962_T5", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 2308, 2313 ] ], "normalized": [] } ]

[ { "id": "PMID-1386962_E1", "type": "Negative_regulation", "trigger": { "text": [ "inversion" ], "offsets": [ [ 1707, 1716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_E2" } ] }, { "id": "PMID-1386962_E2", "type": "Positive_regulation", "trigger": { "text": [ "responsiveness" ], "offsets": [ [ 1728, 1742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_E3" } ] }, { "id": "PMID-1386962_E3", "type": "Positive_regulation", "trigger": { "text": [ "turning" ], "offsets": [ [ 1755, 1762 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_E4" } ] }, { "id": "PMID-1386962_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1771, 1781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_T1" } ] }, { "id": "PMID-1386962_E5", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 2056, 2062 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_E6" } ] }, { "id": "PMID-1386962_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2075, 2085 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_T2" } ] }, { "id": "PMID-1386962_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2243, 2253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_T4" } ] }, { "id": "PMID-1386962_E8", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 2314, 2323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1386962_T5" } ] } ]

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[ { "id": "PMID-1419903__text", "type": "abstract", "text": [ "Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. \nThe present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1831 ] ] } ]

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"Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 213, 223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E7" } ] }, { "id": "PMID-1419903_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 233, 243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T4" } ] }, { "id": "PMID-1419903_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 373, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E12" } ] }, { "id": "PMID-1419903_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 373, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E10" } ] }, { "id": "PMID-1419903_E10", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 463, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E11" } ] }, { "id": "PMID-1419903_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 503, 513 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T5" } ] }, { "id": "PMID-1419903_E12", "type": "Negative_regulation", "trigger": { "text": [ "down-regulation" ], "offsets": [ [ 519, 534 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E13" } ] }, { "id": "PMID-1419903_E13", "type": "Transcription", "trigger": { "text": [ "transcripts" ], "offsets": [ [ 544, 555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T6" } ] }, { "id": "PMID-1419903_E14", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 691, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E15" } ] }, { "id": "PMID-1419903_E15", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 715, 721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T7" } ] }, { "id": "PMID-1419903_E16", "type": "Positive_regulation", "trigger": { "text": [ "Similar effects" ], "offsets": [ [ 750, 765 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T8" } ] }, { "id": "PMID-1419903_E17", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 856, 869 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T9" } ] }, { "id": "PMID-1419903_E18", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 907, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E17" } ] }, { "id": "PMID-1419903_E19", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 983, 989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T10" } ] }, { "id": "PMID-1419903_E20", "type": "Positive_regulation", "trigger": { "text": [ "superinduced" ], "offsets": [ [ 995, 1007 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E19" } ] }, { "id": "PMID-1419903_E21", "type": "Positive_regulation", "trigger": { "text": [ "superinduced" ], "offsets": [ [ 995, 1007 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E20" } ] }, { "id": "PMID-1419903_E22", "type": "Regulation", "trigger": { "text": [ "had little, if any, effect" ], "offsets": [ [ 1107, 1133 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E23" } ] }, { "id": "PMID-1419903_E23", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1150, 1157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E24" } ] }, { "id": "PMID-1419903_E24", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1164, 1177 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T11" } ] }, { "id": "PMID-1419903_E25", "type": "Positive_regulation", "trigger": { "text": [ "stabilization" ], "offsets": [ [ 1365, 1378 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T13" } ] }, { "id": "PMID-1419903_E26", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1467, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E27" } ] }, { "id": "PMID-1419903_E27", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1486, 1499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T14" } ] }, { "id": "PMID-1419903_E28", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1519, 1529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_E26" } ] }, { "id": "PMID-1419903_E29", "type": "Positive_regulation", "trigger": { "text": [ "autoinduced" ], "offsets": [ [ 1636, 1647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419903_T15" } ] } ]

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[]

[ { "id": "PMID-1419905__text", "type": "abstract", "text": [ "Activation of NF-kappa B by interleukin 2 in human blood monocytes. \nWe report here that interleukin 2 (IL-2) acts on human blood monocytes by enhancing binding activity of the transcription factor NF-kappa B to its consensus sequence in the 5' regulatory enhancer region of the IL-2 receptor alpha chain (p55). Similarly, IL-2 activates NF-kappa B in the human monocytic cell line U 937, but not in resting human T-cells. This effect is detectable within 15 min and peaks 1 h after exposure to IL-2. Enhanced NF-kappa B binding activity is followed by functional activation in that inducibility of the IL-2 receptor alpha chain is mediated by enhanced NF-kappa B binding and that a heterologous promoter containing the NF-kappa B consensus sequence (-291 to -245) of the IL-2 receptor alpha chain gene is activated. In addition, IL-2 is capable of increasing transcript levels of the p50 gene coding for the p50 subunit of the NF-kappa B transcription factor, whereas mRNA levels of the p65 NF-kappa B gene remained unchanged. " ], "offsets": [ [ 0, 1028 ] ] } ]

[ { "id": "PMID-1419905_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 28, 41 ] ], "normalized": [] }, { "id": "PMID-1419905_T2", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 89, 102 ] ], "normalized": [] }, { "id": "PMID-1419905_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 104, 108 ] ], "normalized": [] }, { "id": "PMID-1419905_T4", "type": "Protein", "text": [ "IL-2 receptor alpha chain" ], "offsets": [ [ 279, 304 ] ], "normalized": [] }, { "id": "PMID-1419905_T5", "type": "Protein", "text": [ "p55" ], "offsets": [ [ 306, 309 ] ], "normalized": [] }, { "id": "PMID-1419905_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 323, 327 ] ], "normalized": [] }, { "id": "PMID-1419905_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 495, 499 ] ], "normalized": [] }, { "id": "PMID-1419905_T8", "type": "Protein", "text": [ "IL-2 receptor alpha chain" ], "offsets": [ [ 603, 628 ] ], "normalized": [] }, { "id": "PMID-1419905_T9", "type": "Protein", "text": [ "IL-2 receptor alpha chain" ], "offsets": [ [ 772, 797 ] ], "normalized": [] }, { "id": "PMID-1419905_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 830, 834 ] ], "normalized": [] }, { "id": "PMID-1419905_T11", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 885, 888 ] ], "normalized": [] }, { "id": "PMID-1419905_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 909, 912 ] ], "normalized": [] }, { "id": "PMID-1419905_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 988, 991 ] ], "normalized": [] } ]

[ { "id": "PMID-1419905_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 143, 152 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_E2" }, { "role": "Cause", "ref_id": "PMID-1419905_T3" } ] }, { "id": "PMID-1419905_E2", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 153, 169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_T4" } ] }, { "id": "PMID-1419905_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducibility" ], "offsets": [ [ 583, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_T8" } ] }, { "id": "PMID-1419905_E4", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 632, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_E3" } ] }, { "id": "PMID-1419905_E5", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 806, 815 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_T9" } ] }, { "id": "PMID-1419905_E6", "type": "Positive_regulation", "trigger": { "text": [ "increasing" ], "offsets": [ [ 849, 859 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_E7" }, { "role": "Cause", "ref_id": "PMID-1419905_T10" } ] }, { "id": "PMID-1419905_E7", "type": "Transcription", "trigger": { "text": [ "transcript levels" ], "offsets": [ [ 860, 877 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_T11" } ] }, { "id": "PMID-1419905_E8", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 969, 980 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_T13" } ] }, { "id": "PMID-1419905_E9", "type": "Positive_regulation", "trigger": { "text": [ "unchanged" ], "offsets": [ [ 1017, 1026 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1419905_E8" }, { "role": "Cause", "ref_id": "PMID-1419905_T10" } ] } ]

[ { "id": "PMID-1419905_1", "entity_ids": [ "PMID-1419905_T3", "PMID-1419905_T2" ] }, { "id": "PMID-1419905_2", "entity_ids": [ "PMID-1419905_T4", "PMID-1419905_T5" ] } ]

[]

[ { "id": "PMID-1429562__text", "type": "abstract", "text": [ "The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines. \nThe 1311-base pair human tumor necrosis factor (TNF) alpha promoter region was fused to the luciferase (Luc) reporter gene and studied in a transient transfection system in three TNF producing cell lines, the U937 macrophage cell line, the MLA 144 T cell line, and the 729-6 B cell line. This full length promoter construct can be induced by phorbol 13-myristate acetate (PMA) in each of these cell types. Analysis of a series of 5'-truncations showed several peaks of basal and PMA induced activity suggesting the presence of several positive and negative regulatory elements. A PMA responsive element was localized to a region between -95 and -36 bp relative to the transcription start site. Within this region, single AP-2- and AP-1- like consensus sequences were noted. These AP-2 and AP-1 sites were each modified with a double point mutation. A modest (20-50%) reduction in TNF promoter activity was observed with the AP-2 site mutation. However, mutation of the AP-1 site markedly diminished both the basal and PMA-activated promoter activity. Also co-transfections of the wild-type promoter construct with an AP-1/c-jun expression vector resulted in augmented basal and PMA-induced promoter activity. " ], "offsets": [ [ 0, 1323 ] ] } ]

[ { "id": "PMID-1429562_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 28, 55 ] ], "normalized": [] }, { "id": "PMID-1429562_T2", "type": "Protein", "text": [ "tumor necrosis factor (TNF) alpha" ], "offsets": [ [ 139, 172 ] ], "normalized": [] }, { "id": "PMID-1429562_T3", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 994, 997 ] ], "normalized": [] }, { "id": "PMID-1429562_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1236, 1241 ] ], "normalized": [] }, { "id": "PMID-1429562_T6", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 56, 71 ] ], "normalized": [] }, { "id": "PMID-1429562_T7", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 173, 188 ] ], "normalized": [] }, { "id": "PMID-1429562_T10", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 998, 1006 ] ], "normalized": [] } ]

[ { "id": "PMID-1429562_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 4, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T1" }, { "role": "Site", "ref_id": "PMID-1429562_T6" } ] }, { "id": "PMID-1429562_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 445, 452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T2" }, { "role": "Site", "ref_id": "PMID-1429562_T7" } ] }, { "id": "PMID-1429562_E3", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 981, 990 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T3" }, { "role": "Site", "ref_id": "PMID-1429562_T10" } ] }, { "id": "PMID-1429562_E4", "type": "Negative_regulation", "trigger": { "text": [ "diminished" ], "offsets": [ [ 1102, 1112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_E6" } ] }, { "id": "PMID-1429562_E5", "type": "Negative_regulation", "trigger": { "text": [ "diminished" ], "offsets": [ [ 1102, 1112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T3" }, { "role": "Site", "ref_id": "PMID-1429562_T10" } ] }, { "id": "PMID-1429562_E6", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1136, 1145 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T3" }, { "role": "Site", "ref_id": "PMID-1429562_T10" } ] }, { "id": "PMID-1429562_E7", "type": "Gene_expression", "trigger": { "text": [ "co-transfections" ], "offsets": [ [ 1170, 1186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T4" } ] }, { "id": "PMID-1429562_E8", "type": "Positive_regulation", "trigger": { "text": [ "co-transfections" ], "offsets": [ [ 1170, 1186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_E7" } ] }, { "id": "PMID-1429562_E9", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 1272, 1281 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T3" }, { "role": "Cause", "ref_id": "PMID-1429562_E8" }, { "role": "Site", "ref_id": "PMID-1429562_T10" } ] }, { "id": "PMID-1429562_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1296, 1303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1429562_T3" }, { "role": "Site", "ref_id": "PMID-1429562_T10" } ] } ]

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[ { "id": "PMID-1431113__text", "type": "abstract", "text": [ "Redox status of cells influences constitutive or induced NF-kappa B translocation and HIV long terminal repeat activity in human T and monocytic cell lines. \nWe have tested the hypothesis that cellular activation events occurring in T lymphocytes and monocytes and mediated through translocation of the transcription factor NF-kappa B are dependent upon the constitutive redox status of these cells. We used phenolic, lipid-soluble, chain-breaking antioxidants (butylated hydroxyanisole (BHA), nordihydroquairetic acid, or alpha-tocopherol (vitamin E) to show that peroxyl radical scavenging in unstimulated and PMA- or TNF-stimulated cells blocks the functions depending on NF-kappa B activation. BHA was found to suppress not only PMA- or TNF-induced, but also constitutive, HIV-enhancer activity concomitant to an inhibition of NF-kappa B binding activity in both lymphoblastoid T (J.Jhan) and monocytic (U937) cell lines. This was also true for KBF (p50 homodimer) binding activity in U937 cells. Secretion of TNF, the product of another NF-kappa B-dependent gene, was abolished by BHA in PMA-stimulated U937 cells. The anti-oxidative effect of BHA was accompanied by an increase in thiol, but not glutathione, content in stimulated and unstimulated T cell, whereas TNF stimulation itself barely modified the cellular thiol level. Oxidative stress obtained by the addition of H2O2 to the culture medium of J.Jhan or U937 cells could not by itself induce NF-kappa B activation. These observations suggest that TNF and PMA do not lead to NF-kappa B activation through induction of changes in the cell redox status. Rather, TNF and PMA can exert their effect only if cells are in an appropriate redox status, because prior modification toward reduction with BHA treatment prevents this activation. It appears that a basal redox equilibrium tending toward oxidation is a prerequisite for full activation of transduction pathways regulating the activity of NF-kappa B-dependent genes. " ], "offsets": [ [ 0, 1984 ] ] } ]

[ { "id": "PMID-1431113_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 954, 957 ] ], "normalized": [] } ]

[ { "id": "PMID-1431113_E1", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 969, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1431113_T1" } ] } ]

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[ { "id": "PMID-1448931__text", "type": "abstract", "text": [ "Natural variants of the HIV-1 long terminal repeat: analysis of promoters with duplicated DNA regulatory motifs. \nSequence variation in the long terminal repeat (LTR) region of HIV-1 was analyzed in viral isolates of 17 infected individuals. Two classes of LTR size variants were found. One HIV-1 variant was detected containing an additional binding site for the transcription factor Sp1. Another LTR size variation was observed in four patients in a region just upstream of the NF-kappa B enhancer. This variation was the result of a duplication of a short DNA sequence (CTG-motif). Cell culture experiments demonstrated that the natural variant with four Sp1 sites had a slightly higher promoter activity and viral replication rate than the isogenic control LTR with three Sp1 sites. No positive effect of the duplicated CTG-motif could be detected. In order to measure small differences in virus production more accurately, equal amounts of a size variant and the wild-type plasmid were cotransfected into T-cells. The virus with four Sp1 sites did outgrow the three Sp1 virus in 35 days of culture and CTG-monomer virus outcompeted the CTG-dimer virus in 42 days. Based on these results we estimate a 5-10% difference in virus production of the LTR variants when compared to that of wild-type. " ], "offsets": [ [ 0, 1299 ] ] } ]

[ { "id": "PMID-1448931_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 385, 388 ] ], "normalized": [] }, { "id": "PMID-1448931_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 658, 661 ] ], "normalized": [] }, { "id": "PMID-1448931_T3", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 776, 779 ] ], "normalized": [] }, { "id": "PMID-1448931_T4", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "PMID-1448931_T5", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] } ]

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[ { "id": "PMID-1454801__text", "type": "abstract", "text": [ "Transcription of the hypersensitive site HS2 enhancer in erythroid cells. \nIn the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site. " ], "offsets": [ [ 0, 1399 ] ] } ]

[ { "id": "PMID-1454801_T1", "type": "Protein", "text": [ "beta-like globin" ], "offsets": [ [ 198, 214 ] ], "normalized": [] }, { "id": "PMID-1454801_T2", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 429, 462 ] ], "normalized": [] }, { "id": "PMID-1454801_T3", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "PMID-1454801_T4", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 725, 728 ] ], "normalized": [] }, { "id": "PMID-1454801_T5", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1057, 1060 ] ], "normalized": [] } ]

[ { "id": "PMID-1454801_E1", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 152, 161 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1454801_E2" } ] }, { "id": "PMID-1454801_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 166, 179 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1454801_T1" } ] } ]

[ { "id": "PMID-1454801_1", "entity_ids": [ "PMID-1454801_T2", "PMID-1454801_T3" ] } ]

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[ { "id": "PMID-1464736__text", "type": "abstract", "text": [ "Phorbol ester reduces constitutive nuclear NF kappa B and inhibits HIV-1 production in mature human monocytic cells. \nNF kappa B is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocytic leukemias. There is little information available on the response of NF kappa B to cytokines in normal human monocytes. We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NF kappa B binding sequence, as a probe in a gel retardation assay to study this transcription factor. Using this assay, we have detected NF kappa B in extracts of nuclei from normal human monocytes. Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NF kappa B from nuclear extracts of monocytes. A similar result was obtained with the mature monocytic leukemia cell line THP-1. The constitutive transcription factor SP1 was unaffected by addition of TPA. The disappearance of NF kappa B from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester. In THP-1 cells, TPA also induced a new, faster-migrating NF kappa B species not induced in monocytes. Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner. These results are in striking contrast to the increase in nuclear NF kappa B and HIV-1 replication induced by phorbol esters in promonocytic leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes. " ], "offsets": [ [ 0, 1922 ] ] } ]

[ { "id": "PMID-1464736_T1", "type": "Protein", "text": [ "SP1" ], "offsets": [ [ 1050, 1053 ] ], "normalized": [] } ]

[ { "id": "PMID-1464736_E1", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1058, 1068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1464736_T1" } ] } ]

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[ { "id": "PMID-1470918__text", "type": "abstract", "text": [ "Targeted degradation of c-Fos, but not v-Fos, by a phosphorylation-dependent signal on c-Jun. \nThe proto-oncogene products c-Fos and c-Jun heterodimerize through their leucine zippers to form the AP-1 transcription factor. The transcriptional activity of the heterodimer is regulated by signal-dependent phosphorylation and dephosphorylation events. The stability of c-Fos was found to also be controlled by intracellular signal transduction. In transient expression and in vitro degradation experiments, the stability of c-Fos was decreased when the protein was dimerized with phosphorylated c-Jun. c-Jun protein isolated from phorbol ester-induced cells did not target c-Fos for degradation, which suggests that c-Fos is transiently stabilized after stimulation of cell growth. v-Fos protein, the retroviral counterpart of c-Fos, was not susceptible to degradation targeted by c-Jun. " ], "offsets": [ [ 0, 886 ] ] } ]

[ { "id": "PMID-1470918_T1", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 24, 29 ] ], "normalized": [] }, { "id": "PMID-1470918_T2", "type": "Protein", "text": [ "v-Fos" ], "offsets": [ [ 39, 44 ] ], "normalized": [] }, { "id": "PMID-1470918_T3", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 87, 92 ] ], "normalized": [] }, { "id": "PMID-1470918_T4", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMID-1470918_T5", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 133, 138 ] ], "normalized": [] }, { "id": "PMID-1470918_T6", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 367, 372 ] ], "normalized": [] }, { "id": "PMID-1470918_T7", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 522, 527 ] ], "normalized": [] }, { "id": "PMID-1470918_T8", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 593, 598 ] ], "normalized": [] }, { "id": "PMID-1470918_T9", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-1470918_T10", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "PMID-1470918_T11", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 714, 719 ] ], "normalized": [] }, { "id": "PMID-1470918_T12", "type": "Protein", "text": [ "v-Fos" ], "offsets": [ [ 780, 785 ] ], "normalized": [] }, { "id": "PMID-1470918_T13", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 825, 830 ] ], "normalized": [] }, { "id": "PMID-1470918_T14", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 879, 884 ] ], "normalized": [] } ]

[ { "id": "PMID-1470918_E1", "type": "Positive_regulation", "trigger": { "text": [ "Targeted" ], "offsets": [ [ 0, 8 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E4" } ] }, { "id": "PMID-1470918_E2", "type": "Positive_regulation", "trigger": { "text": [ "Targeted" ], "offsets": [ [ 0, 8 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E3" } ] }, { "id": "PMID-1470918_E3", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 9, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T2" } ] }, { "id": "PMID-1470918_E4", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 9, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T1" } ] }, { "id": "PMID-1470918_E5", "type": "Binding", "trigger": { "text": [ "heterodimerize" ], "offsets": [ [ 139, 153 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T4" }, { "role": "Theme", "ref_id": "PMID-1470918_T5" } ] }, { "id": "PMID-1470918_E6", "type": "Positive_regulation", "trigger": { "text": [ "through" ], "offsets": [ [ 154, 161 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E5" } ] }, { "id": "PMID-1470918_E7", "type": "Protein_catabolism", "trigger": { "text": [ "stability" ], "offsets": [ [ 354, 363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T6" } ] }, { "id": "PMID-1470918_E8", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 394, 404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E7" } ] }, { "id": "PMID-1470918_E9", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 532, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T7" } ] }, { "id": "PMID-1470918_E10", "type": "Positive_regulation", "trigger": { "text": [ "when" ], "offsets": [ [ 542, 546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E9" }, { "role": "Cause", "ref_id": "PMID-1470918_E11" } ] }, { "id": "PMID-1470918_E11", "type": "Binding", "trigger": { "text": [ "dimerized" ], "offsets": [ [ 563, 572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T7" }, { "role": "Theme", "ref_id": "PMID-1470918_T8" } ] }, { "id": "PMID-1470918_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 578, 592 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T8" } ] }, { "id": "PMID-1470918_E13", "type": "Positive_regulation", "trigger": { "text": [ "target" ], "offsets": [ [ 664, 670 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E14" }, { "role": "Cause", "ref_id": "PMID-1470918_T9" } ] }, { "id": "PMID-1470918_E14", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 681, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T10" } ] }, { "id": "PMID-1470918_E15", "type": "Protein_catabolism", "trigger": { "text": [ "stabilized" ], "offsets": [ [ 735, 745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T11" } ] }, { "id": "PMID-1470918_E16", "type": "Positive_regulation", "trigger": { "text": [ "after" ], "offsets": [ [ 746, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_E15" } ] }, { "id": "PMID-1470918_E17", "type": "Positive_regulation", "trigger": { "text": [ "susceptible" ], "offsets": [ [ 840, 851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T12" } ] }, { "id": "PMID-1470918_E18", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 855, 866 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T12" } ] }, { "id": "PMID-1470918_E19", "type": "Binding", "trigger": { "text": [ "targeted" ], "offsets": [ [ 867, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1470918_T12" }, { "role": "Theme", "ref_id": "PMID-1470918_T14" } ] } ]

[]

[]

[ { "id": "PMID-1482376__text", "type": "abstract", "text": [ "Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. \nAcquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV). The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor kappa B (NF-kappa B), and this transcriptional activator appears to regulate HIV activation. Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-kappa B activation. The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF-kappa B and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS. Incubation of Jurkat T cells (1 x 10(6) cells/ml) with a natural thiol antioxidant, alpha-lipoic acid, prior to the stimulation of cells was found to inhibit NF-kappa B activation induced by tumor necrosis factor-alpha (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml). The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine. These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics. " ], "offsets": [ [ 0, 1280 ] ] } ]

[ { "id": "PMID-1482376_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 935, 962 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-1492121__text", "type": "abstract", "text": [ "Activation of lymphokine genes in T cells: role of cis-acting DNA elements that respond to T cell activation signals. \nActivation of T cells is initiated by the recognition of antigen on antigen presenting cells to exert the effector functions in immune and inflammatory responses. Two types of helper T cell (Th) clones (Th1 and Th2) are defined on the basis of different patterns of cytokine (lymphokine) secretion. They determine the outcome of an antigenic response toward humoral or cell-mediated immunity. Although lymphokine genes are coordinately regulated upon antigen stimulation, they are regulated by the mechanisms common to all as well as those which are unique to each gene. For most lymphokine genes, a combination of phorbol esters (phorbol 12-myristate 13 acetate, PMA) and calcium ionophores (A23187) is required for their maximal induction. Yet phorbol ester alone or calcium ionophore alone produce several lymphokines. The production of the granulocyte-macrophage colony stimulating factor (GM-CSF) is completely dependent on the two signals. We have previously found a cis-acting region spanning the GM-CSF promoter region (positions -95 to +27) that confers inducibility to reporter genes in transient transfection assays. Further analysis identified three elements required for efficient induction, referred to as GM2, GC-box and conserved lymphokine element (CLE0). GM2 defines a binding site for protein(s) whose binding is inducible by PMA. One protein, NF-GM2 is similar to the transcription factor NF-kB. GC-box is a binding site for constitutively bound proteins. CLEO defines a binding site for protein(s) whose optimum binding is stimulated by PMA and A23187. Viral trans-activators such as Tax (human T cell leukemia virus-1, HTLV-1) and E2 (bovine papilloma virus, BPV) proteins are other agents which activate lymphokine gene expression by bypassing T cell receptor (TCR) mediated signaling. The trans-activation domain of E2 and Tax is interchangeable although they have no obvious sequence homology between them. The viral trans-activators appear to target specific DNA binding protein such as NF-kB and Sp1 to cis-acting DNA site and promote lymphokine gene expression without TCR-mediated stimulation. " ], "offsets": [ [ 0, 2242 ] ] } ]

[ { "id": "PMID-1492121_T1", "type": "Protein", "text": [ "granulocyte-macrophage colony stimulating factor" ], "offsets": [ [ 963, 1011 ] ], "normalized": [] }, { "id": "PMID-1492121_T2", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1013, 1019 ] ], "normalized": [] }, { "id": "PMID-1492121_T3", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1123, 1129 ] ], "normalized": [] }, { "id": "PMID-1492121_T4", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1724, 1727 ] ], "normalized": [] }, { "id": "PMID-1492121_T5", "type": "Protein", "text": [ "E2" ], "offsets": [ [ 1772, 1774 ] ], "normalized": [] }, { "id": "PMID-1492121_T6", "type": "Protein", "text": [ "E2" ], "offsets": [ [ 1959, 1961 ] ], "normalized": [] }, { "id": "PMID-1492121_T7", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1966, 1969 ] ], "normalized": [] }, { "id": "PMID-1492121_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 2142, 2145 ] ], "normalized": [] } ]

[ { "id": "PMID-1492121_E1", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 945, 955 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1492121_T2" } ] }, { "id": "PMID-1492121_E2", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1492121_E1" } ] }, { "id": "PMID-1492121_E3", "type": "Binding", "trigger": { "text": [ "target" ], "offsets": [ [ 2088, 2094 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1492121_T8" } ] }, { "id": "PMID-1492121_E4", "type": "Positive_regulation", "trigger": { "text": [ "target" ], "offsets": [ [ 2088, 2094 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1492121_E3" }, { "role": "Cause", "ref_id": "PMID-1492121_T4" } ] }, { "id": "PMID-1492121_E5", "type": "Positive_regulation", "trigger": { "text": [ "target" ], "offsets": [ [ 2088, 2094 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1492121_E3" }, { "role": "Cause", "ref_id": "PMID-1492121_T5" } ] } ]

[ { "id": "PMID-1492121_1", "entity_ids": [ "PMID-1492121_T2", "PMID-1492121_T1" ] } ]

[]

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

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

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[ { "id": "PMID-1502179__text", "type": "abstract", "text": [ "Simple derivation of TFIID-dependent RNA polymerase II transcription systems from Schizosaccharomyces pombe and other organisms, and factors required for transcriptional activation. \nResolution of whole cell extract through two chromatographic steps yields a single protein fraction requiring only the addition of TFIID for the initiation of transcription at RNA polymerase II promoters. This approach allows the convenient generation of RNA polymerase II transcription systems from Saccharomyces cerevisiae, human lymphocytes, and Schizosaccharomyces pombe. TFIIDs from all three organisms are interchangeable among all three systems. The S. cerevisiae and Sch. pombe systems support effects of acidic activator proteins, provided a further protein fraction from S. cerevisiae is supplied. This further fraction is distinct from the mediator of transcriptional activation described previously and represents a second component in addition to general initiation factors that may facilitate a response to acidic activators. " ], "offsets": [ [ 0, 1023 ] ] } ]

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[ { "id": "PMID-1502202__text", "type": "abstract", "text": [ "NF-kappa B-dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells. \nThe molecular mechanisms underlying the sustained nuclear translocation of NF-kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus (HIV) were studied. The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells. Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif, by bona fide p50/p65 heterodimers. Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV-infected cells. In contrast to the transient NF-kappa B activation induced by phorbol ester, the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor (GF 109203X). These observations indicate that during chronic HIV infection of U937 cells, continuous NF-kappa B (p50/p65) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation, ready for further translocation. This HIV-mediated mechanism results in a self-perpetuating loop of NF-kappa B production. " ], "offsets": [ [ 0, 1350 ] ] } ]

[ { "id": "PMID-1502202_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 49, 52 ] ], "normalized": [] }, { "id": "PMID-1502202_T2", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 425, 429 ] ], "normalized": [] }, { "id": "PMID-1502202_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 458, 461 ] ], "normalized": [] }, { "id": "PMID-1502202_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 641, 644 ] ], "normalized": [] }, { "id": "PMID-1502202_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 645, 648 ] ], "normalized": [] }, { "id": "PMID-1502202_T6", "type": "Protein", "text": [ "PKC isoenzymes alpha" ], "offsets": [ [ 927, 947 ] ], "normalized": [] }, { "id": "PMID-1502202_T7", "type": "Protein", "text": [ "beta" ], "offsets": [ [ 952, 956 ] ], "normalized": [] }, { "id": "PMID-1502202_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1115, 1118 ] ], "normalized": [] }, { "id": "PMID-1502202_T9", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1119, 1122 ] ], "normalized": [] }, { "id": "PMID-1502202_T10", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1149, 1153 ] ], "normalized": [] }, { "id": "PMID-1502202_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 66, 74 ] ], "normalized": [] }, { "id": "PMID-1502202_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1154, 1162 ] ], "normalized": [] } ]

[ { "id": "PMID-1502202_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 21, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T1" }, { "role": "Site", "ref_id": "PMID-1502202_T12" } ] }, { "id": "PMID-1502202_E2", "type": "Regulation", "trigger": { "text": [ "underlies" ], "offsets": [ [ 75, 84 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E3" }, { "role": "Cause", "ref_id": "PMID-1502202_E1" } ] }, { "id": "PMID-1502202_E3", "type": "Positive_regulation", "trigger": { "text": [ "perpetuation" ], "offsets": [ [ 90, 102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E4" } ] }, { "id": "PMID-1502202_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 135, 148 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T1" } ] }, { "id": "PMID-1502202_E5", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 393, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E6" } ] }, { "id": "PMID-1502202_E6", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 408, 417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T2" } ] }, { "id": "PMID-1502202_E7", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 474, 482 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E5" } ] }, { "id": "PMID-1502202_E8", "type": "Regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 563, 571 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E7" } ] }, { "id": "PMID-1502202_E9", "type": "Regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 563, 571 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E7" }, { "role": "Cause", "ref_id": "PMID-1502202_T5" } ] }, { "id": "PMID-1502202_E10", "type": "Regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 563, 571 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E7" }, { "role": "Cause", "ref_id": "PMID-1502202_T4" } ] }, { "id": "PMID-1502202_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 991, 1000 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T7" } ] }, { "id": "PMID-1502202_E12", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 991, 1000 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T6" } ] }, { "id": "PMID-1502202_E13", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1124, 1137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T8" } ] }, { "id": "PMID-1502202_E14", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1124, 1137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T9" } ] }, { "id": "PMID-1502202_E15", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1138, 1145 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E17" }, { "role": "Cause", "ref_id": "PMID-1502202_E14" } ] }, { "id": "PMID-1502202_E16", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1138, 1145 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_E17" }, { "role": "Cause", "ref_id": "PMID-1502202_E13" } ] }, { "id": "PMID-1502202_E17", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1163, 1175 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1502202_T10" }, { "role": "Site", "ref_id": "PMID-1502202_T23" } ] } ]

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[ { "id": "PMID-1505523__text", "type": "abstract", "text": [ "TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. \nThe Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1800 ] ] } ]

[ { "id": "PMID-1505523_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "PMID-1505523_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 119, 122 ] ], "normalized": [] }, { "id": "PMID-1505523_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 265, 268 ] ], "normalized": [] }, { "id": "PMID-1505523_T4", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 704, 707 ] ], "normalized": [] }, { "id": "PMID-1505523_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 994, 997 ] ], "normalized": [] }, { "id": "PMID-1505523_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "PMID-1505523_T7", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1298, 1301 ] ], "normalized": [] }, { "id": "PMID-1505523_T8", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 1753, 1756 ] ], "normalized": [] } ]

[ { "id": "PMID-1505523_E1", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 689, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1505523_T4" } ] }, { "id": "PMID-1505523_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1733, 1743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1505523_T8" } ] } ]

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[ { "id": "PMID-1510878__text", "type": "abstract", "text": [ "Mitogen stimulation of T-cells increases c-Fos and c-Jun protein levels, AP-1 binding and AP-1 transcriptional activity. \nWe have analysed the effect of mitogenic lectins on c-Fos and c-Jun protein levels as well as on activator protein-1 (AP-1) binding and enhancer activity in Jurkat T-cells. Both c-Fos and c-Jun protein levels were increased after Con A and PHA stimulation. Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C (PKC), the possible involvement of these intracellular messengers in c-Fos and c-Jun induction was tested. PMA, which directly activates PKC, mimicked the effect of the lectins on c-Fos and c-Jun, but elevation of either intracellular Ca2+ or cAMP levels had little or no effect. The mitogen-induced increase of c-Fos and c-Jun immunoreactivity was inhibited by H-7, a kinase inhibitor with relatively high specificity for PKC, and less efficiently by H-8, a structurally related kinase inhibitor less active on PKC, but more active on cyclic nucleotide-dependent kinases. Con A stimulation was found to increase both binding of AP-1 to the AP-1 consensus sequence, TRE, and AP-1 enhancer activity, in Jurkat cells. PMA was also found to increase the AP-1 enhancer activity, whereas elevation of Ca2+ or cAMP had only minor effects. We conclude that stimulation with mitogenic lectins is sufficient to increase both c-Fos and c-Jun protein levels, AP-1 binding and AP-1 enhancer activity in Jurkat cells and that they act via mechanisms that could involve the activation of PKC. " ], "offsets": [ [ 0, 1564 ] ] } ]

[ { "id": "PMID-1510878_T1", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 41, 46 ] ], "normalized": [] }, { "id": "PMID-1510878_T2", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-1510878_T3", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 174, 179 ] ], "normalized": [] }, { "id": "PMID-1510878_T4", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 184, 189 ] ], "normalized": [] }, { "id": "PMID-1510878_T5", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 300, 305 ] ], "normalized": [] }, { "id": "PMID-1510878_T6", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 310, 315 ] ], "normalized": [] }, { "id": "PMID-1510878_T7", "type": "Protein", "text": [ "Con A" ], "offsets": [ [ 352, 357 ] ], "normalized": [] }, { "id": "PMID-1510878_T8", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 554, 559 ] ], "normalized": [] }, { "id": "PMID-1510878_T9", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 564, 569 ] ], "normalized": [] }, { "id": "PMID-1510878_T10", "type": "Protein", "text": [ "PKC" ], "offsets": [ [ 622, 625 ] ], "normalized": [] }, { "id": "PMID-1510878_T11", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 665, 670 ] ], "normalized": [] }, { "id": "PMID-1510878_T12", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 675, 680 ] ], "normalized": [] }, { "id": "PMID-1510878_T13", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 797, 802 ] ], "normalized": [] }, { "id": "PMID-1510878_T14", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 807, 812 ] ], "normalized": [] }, { "id": "PMID-1510878_T15", "type": "Protein", "text": [ "PKC" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "PMID-1510878_T16", "type": "Protein", "text": [ "PKC" ], "offsets": [ [ 997, 1000 ] ], "normalized": [] }, { "id": "PMID-1510878_T17", "type": "Protein", "text": [ "Con A" ], "offsets": [ [ 1058, 1063 ] ], "normalized": [] }, { "id": "PMID-1510878_T18", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1401, 1406 ] ], "normalized": [] }, { "id": "PMID-1510878_T19", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1411, 1416 ] ], "normalized": [] }, { "id": "PMID-1510878_T20", "type": "Protein", "text": [ "PKC" ], "offsets": [ [ 1559, 1562 ] ], "normalized": [] } ]

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"Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 336, 345 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T6" } ] }, { "id": "PMID-1510878_E7", "type": "Regulation", "trigger": { "text": [ "involvement" ], "offsets": [ [ 505, 516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_E9" } ] }, { "id": "PMID-1510878_E8", "type": "Regulation", "trigger": { "text": [ "involvement" ], "offsets": [ [ 505, 516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_E10" } ] }, { "id": "PMID-1510878_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 570, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T9" } ] }, { "id": "PMID-1510878_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 570, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T8" } ] }, { "id": "PMID-1510878_E11", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 612, 621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T10" } ] }, { "id": "PMID-1510878_E12", "type": "Positive_regulation", "trigger": { "text": [ "mimicked the effect of the lectins" ], "offsets": [ [ 627, 661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T11" } ] }, { "id": "PMID-1510878_E13", "type": "Positive_regulation", "trigger": { "text": [ "mimicked the effect of the lectins" ], "offsets": [ [ 627, 661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T12" } ] }, { "id": "PMID-1510878_E14", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 757, 763 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T11" } ] }, { "id": "PMID-1510878_E15", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 757, 763 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T12" } ] }, { "id": "PMID-1510878_E16", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 785, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_E18" } ] }, { "id": "PMID-1510878_E17", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 785, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_E19" } ] }, { "id": "PMID-1510878_E18", "type": "Regulation", "trigger": { "text": [ "immunoreactivity" ], "offsets": [ [ 813, 829 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T14" } ] }, { "id": "PMID-1510878_E19", "type": "Regulation", "trigger": { "text": [ "immunoreactivity" ], "offsets": [ [ 813, 829 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T13" } ] }, { "id": "PMID-1510878_E20", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 834, 843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_E17" } ] }, { "id": "PMID-1510878_E21", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 861, 870 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T15" } ] }, { "id": "PMID-1510878_E22", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 972, 981 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T15" } ] }, { "id": "PMID-1510878_E23", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 972, 981 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T16" } ] }, { "id": "PMID-1510878_E24", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1387, 1395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T19" } ] }, { "id": "PMID-1510878_E25", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1387, 1395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T18" } ] }, { "id": "PMID-1510878_E26", "type": "Regulation", "trigger": { "text": [ "involve" ], "offsets": [ [ 1533, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_E27" } ] }, { "id": "PMID-1510878_E27", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1545, 1555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1510878_T20" } ] } ]

[]

[]

[ { "id": "PMID-1520341__text", "type": "abstract", "text": [ "Okadaic acid is a potent inducer of AP-1, NF-kappa B, and tumor necrosis factor-alpha in human B lymphocytes. \nTreatment of human B lymphocytes with an optimal concentration of okadaic acid, an inhibitor of phosphatases 1 and 2A, resulted in the induction of the transcription factor, AP-1 and a marked increase in NF-kappa B levels. In contrast, no effect on the levels of the octamer binding proteins, Oct-1 or Oct-2, were found. Since both AP-1 and NF-kappa B have been reported to be important in the induction of the tumor necrosis factor-alpha (TNF-alpha) gene we examined the effects of okadaic acid on TNF-alpha mRNA levels. Treatment with okadaic acid resulted in a striking increase in TNF-alpha mRNA transcripts within 1 h of stimulation and large amounts of TNF-alpha were released into the culture media. Although okadaic acid provides a potent inductive signal for AP-1 and NF-kappa B it did not induce either B cell proliferation or immunoglobulin secretion. " ], "offsets": [ [ 0, 974 ] ] } ]

[ { "id": "PMID-1520341_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 58, 85 ] ], "normalized": [] }, { "id": "PMID-1520341_T2", "type": "Protein", "text": [ "phosphatases 1" ], "offsets": [ [ 207, 221 ] ], "normalized": [] }, { "id": "PMID-1520341_T3", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 226, 228 ] ], "normalized": [] }, { "id": "PMID-1520341_T4", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 404, 409 ] ], "normalized": [] }, { "id": "PMID-1520341_T5", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 413, 418 ] ], "normalized": [] }, { "id": "PMID-1520341_T6", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 522, 549 ] ], "normalized": [] }, { "id": "PMID-1520341_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 551, 560 ] ], "normalized": [] }, { "id": "PMID-1520341_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 610, 619 ] ], "normalized": [] }, { "id": "PMID-1520341_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 696, 705 ] ], "normalized": [] }, { "id": "PMID-1520341_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 770, 779 ] ], "normalized": [] } ]

[ { "id": "PMID-1520341_E1", "type": "Positive_regulation", "trigger": { "text": [ "inducer" ], "offsets": [ [ 25, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T1" } ] }, { "id": "PMID-1520341_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 194, 203 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T2" } ] }, { "id": "PMID-1520341_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 194, 203 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T3" } ] }, { "id": "PMID-1520341_E4", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 350, 356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T4" } ] }, { "id": "PMID-1520341_E5", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 350, 356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T5" } ] }, { "id": "PMID-1520341_E6", "type": "Regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 488, 497 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_E8" } ] }, { "id": "PMID-1520341_E7", "type": "Positive_regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 488, 497 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_E8" } ] }, { "id": "PMID-1520341_E8", "type": "Gene_expression", "trigger": { "text": [ "induction" ], "offsets": [ [ 505, 514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T7" } ] }, { "id": "PMID-1520341_E9", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 583, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T8" } ] }, { "id": "PMID-1520341_E10", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 684, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T9" } ] }, { "id": "PMID-1520341_E11", "type": "Positive_regulation", "trigger": { "text": [ "large amounts" ], "offsets": [ [ 753, 766 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_E12" }, { "role": "Cause", "ref_id": "PMID-1520341_E10" } ] }, { "id": "PMID-1520341_E12", "type": "Localization", "trigger": { "text": [ "released" ], "offsets": [ [ 785, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1520341_T10" } ] } ]

[ { "id": "PMID-1520341_1", "entity_ids": [ "PMID-1520341_T7", "PMID-1520341_T6" ] } ]

[]

[ { "id": "PMID-1527846__text", "type": "abstract", "text": [ "A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells. \nHuman immunodeficiency virus type 1 (HIV-1) and HIV-2 are structurally related retroviruses which both cause AIDS in humans. Although both viruses establish latency in quiescent human-peripheral-blood T cells, the asymptomatic phase of HIV-2 infection may be more prolonged than that of HIV-1. The latent phases of both HIV-1 and HIV-2 infection have been shown to be disrupted by T-cell activation, a process that requires host cell transcription factors. In the case of HIV-1, the transcription factor NF-kappa B is sufficient for inducible transcriptional activation. In contrast, factors in addition to NF-kappa B are required to activate HIV-2 transcription in infected T cells. In this report, we demonstrate that a novel Ets-related transcription factor, Elf-1, binds specifically to two purine-rich motifs in the HIV-2 enhancer. Mutagenesis experiments demonstrated that these Elf-1 binding sites are required for induction of HIV-2 transcription following T-cell-receptor-mediated T-cell activation. Moreover, Elf-1 is the only factor present in activated T-cell nuclear extracts that binds to these sites in electrophoretic mobility shift assays. Thus, Elf-1 is a novel transcription factor that appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression. These results may explain differences in the clinical spectra of diseases caused by HIV-1 and HIV-2 and may also have implications for the design of therapeutic approaches to HIV-2 infection. " ], "offsets": [ [ 0, 1673 ] ] } ]

[ { "id": "PMID-1527846_T1", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 42, 47 ] ], "normalized": [] }, { "id": "PMID-1527846_T2", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 938, 943 ] ], "normalized": [] }, { "id": "PMID-1527846_T3", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 1061, 1066 ] ], "normalized": [] }, { "id": "PMID-1527846_T4", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 1195, 1200 ] ], "normalized": [] }, { "id": "PMID-1527846_T5", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 1339, 1344 ] ], "normalized": [] } ]

[ { "id": "PMID-1527846_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 49, 54 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527846_T1" } ] }, { "id": "PMID-1527846_E2", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 945, 950 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527846_T2" } ] }, { "id": "PMID-1527846_E3", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1270, 1275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527846_T4" } ] } ]

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[ { "id": "PMID-1527859__text", "type": "abstract", "text": [ "Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells. \nHuman immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W.C.Greene, N.Engl.J. Med.324:308-317, 1991; S.M.Schnittman, M.C.Psallidopoulos, H.C. Lane, L.Thompson, M.Baseler, F.Massari, C.H.Fox, N.P.Salzman, and A.S.Fauci, Science 245:305-308, 1989). Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T.Folks, D.M.Powell, M.M.Lightfoote, S.Benn, M.A. Martin, and A.S.Fauci, Science 231:600-602, 1986; D.Zagury, J. Bernard, R.Leonard, R.Cheynier, M.Feldman, P.S.Sarin, and R.C. Gallo, Science 231:850-853, 1986). This activation is mediated by the host transcription factor NF-kappa B [G.Nabel and D.Baltimore, Nature (London) 326:711-717, 1987]. We report here that the HIV-1-encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T- cell mitogens. However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT. Additionally, Nef inhibits the induction of HIV-1- and interleukin 2-directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B-binding site. These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters. Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex. " ], "offsets": [ [ 0, 1603 ] ] } ]

[ { "id": "PMID-1527859_T1", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 36, 39 ] ], "normalized": [] }, { "id": "PMID-1527859_T2", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 192, 195 ] ], "normalized": [] }, { "id": "PMID-1527859_T3", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 885, 888 ] ], "normalized": [] }, { "id": "PMID-1527859_T4", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 985, 988 ] ], "normalized": [] }, { "id": "PMID-1527859_T5", "type": "Protein", "text": [ "SP-1" ], "offsets": [ [ 1103, 1107 ] ], "normalized": [] }, { "id": "PMID-1527859_T6", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1144, 1147 ] ], "normalized": [] }, { "id": "PMID-1527859_T7", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 1185, 1198 ] ], "normalized": [] }, { "id": "PMID-1527859_T8", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1386, 1389 ] ], "normalized": [] }, { "id": "PMID-1527859_T9", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 1442, 1455 ] ], "normalized": [] }, { "id": "PMID-1527859_T10", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1498, 1501 ] ], "normalized": [] }, { "id": "PMID-1527859_T15", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 1456, 1465 ] ], "normalized": [] } ]

[ { "id": "PMID-1527859_E1", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 998, 1004 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527859_E2" }, { "role": "Cause", "ref_id": "PMID-1527859_T4" } ] }, { "id": "PMID-1527859_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1013, 1020 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527859_T5" } ] }, { "id": "PMID-1527859_E3", "type": "Positive_regulation", "trigger": { "text": [ "underlie" ], "offsets": [ [ 1377, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527859_E4" } ] }, { "id": "PMID-1527859_E4", "type": "Negative_regulation", "trigger": { "text": [ "negative transcriptional effects" ], "offsets": [ [ 1392, 1424 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1527859_T9" }, { "role": "Site", "ref_id": "PMID-1527859_T15" } ] } ]

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[ { "id": "PMID-1531086__text", "type": "abstract", "text": [ "A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. \nA Rel-related, mitogen-inducible, kappa B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells. The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein. This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa B. Like the 105-kDa precursor, it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats. In vitro-translated proteins, truncated downstream of the Rel domain and excluding the repeats, bind kappa B sites. We refer to the kappa B-binding, truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97. p50B is able to form heteromeric kappa B-binding complexes with RelB, as well as with p65 and p50, the two subunits of NF-kappa B. Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa B site. The data imply the existence of a complex family of NF-kappa B-like transcription factors. " ], "offsets": [ [ 0, 1301 ] ] } ]

[ { "id": "PMID-1531086_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 50, 53 ] ], "normalized": [] }, { "id": "PMID-1531086_T2", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "PMID-1531086_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 435, 438 ] ], "normalized": [] }, { "id": "PMID-1531086_T4", "type": "Protein", "text": [ "p50B" ], "offsets": [ [ 804, 808 ] ], "normalized": [] }, { "id": "PMID-1531086_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 825, 828 ] ], "normalized": [] }, { "id": "PMID-1531086_T6", "type": "Protein", "text": [ "p97" ], "offsets": [ [ 874, 877 ] ], "normalized": [] }, { "id": "PMID-1531086_T7", "type": "Protein", "text": [ "p50B" ], "offsets": [ [ 879, 883 ] ], "normalized": [] }, { "id": "PMID-1531086_T8", "type": "Protein", "text": [ "RelB" ], "offsets": [ [ 943, 947 ] ], "normalized": [] }, { "id": "PMID-1531086_T9", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "PMID-1531086_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "PMID-1531086_T11", "type": "Protein", "text": [ "p50B" ], "offsets": [ [ 1119, 1123 ] ], "normalized": [] }, { "id": "PMID-1531086_T12", "type": "Protein", "text": [ "RelB" ], "offsets": [ [ 1128, 1132 ] ], "normalized": [] }, { "id": "PMID-1531086_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1136, 1139 ] ], "normalized": [] } ]

[ { "id": "PMID-1531086_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 774, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T4" } ] }, { "id": "PMID-1531086_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T10" } ] }, { "id": "PMID-1531086_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T9" } ] }, { "id": "PMID-1531086_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T7" } ] }, { "id": "PMID-1531086_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T8" } ] }, { "id": "PMID-1531086_E6", "type": "Binding", "trigger": { "text": [ "complexes" ], "offsets": [ [ 928, 937 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T7" }, { "role": "Theme", "ref_id": "PMID-1531086_T10" } ] }, { "id": "PMID-1531086_E7", "type": "Binding", "trigger": { "text": [ "complexes" ], "offsets": [ [ 928, 937 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T7" }, { "role": "Theme", "ref_id": "PMID-1531086_T8" } ] }, { "id": "PMID-1531086_E8", "type": "Binding", "trigger": { "text": [ "complexes" ], "offsets": [ [ 928, 937 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531086_T7" }, { "role": "Theme", "ref_id": "PMID-1531086_T9" } ] } ]

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[ { "id": "PMID-1531412__text", "type": "abstract", "text": [ "Transcriptional regulation during T-cell development: the alpha TCR gene as a molecular model. \nThe regulation of gene expression during lymphocyte differentiation is a complex process involving interactions between multiple positive and negative transcriptional regulatory elements. In this article, transcriptional regulation of the archetypal T-cell-specific gene, alpha TCR, is discussed. Major recent developments, including the identification of novel families of transcription factors that regulate multiple T-cell genes during thymocyte ontogeny and T-cell activation, are described. " ], "offsets": [ [ 0, 592 ] ] } ]

[ { "id": "PMID-1531412_T1", "type": "Protein", "text": [ "alpha TCR" ], "offsets": [ [ 58, 67 ] ], "normalized": [] }, { "id": "PMID-1531412_T2", "type": "Protein", "text": [ "alpha TCR" ], "offsets": [ [ 368, 377 ] ], "normalized": [] } ]

[ { "id": "PMID-1531412_E1", "type": "Transcription", "trigger": { "text": [ "Transcriptional" ], "offsets": [ [ 0, 15 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531412_T1" } ] }, { "id": "PMID-1531412_E2", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 16, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531412_E1" } ] }, { "id": "PMID-1531412_E3", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 301, 327 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1531412_T2" } ] } ]

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[ { "id": "PMID-1532661__text", "type": "abstract", "text": [ "An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals. \nWe have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin (IL) 4 gene in Jurkat cells. The human IL-4 gene, of 10 kilobases, is composed of four exons and three introns. A cis-acting element (P sequence) resides in the 5' upstream region; no additional DNA segments with enhancer activity were identified in the human IL-4 gene. For further mapping purposes, a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5' upstream sequence of the IL-4 gene. The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene, and this location was confirmed by base-substitution mutations. The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation. The binding protein(s) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays. The binding of NF(P) (a DNA binding protein that specifically recognizes the P sequence) to the P sequence was abolished when oligonucleotides carrying base substitutions were used, indicating that the NF(P) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo. The P sequence does not share homology with the 5' upstream sequence of the IL-2 gene, even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene. We conclude that a different set of proteins recognize IL-2 and IL-4 genes. " ], "offsets": [ [ 0, 1873 ] ] } ]

[ { "id": "PMID-1532661_T1", "type": "Protein", "text": [ "interleukin 4" ], "offsets": [ [ 66, 79 ] ], "normalized": [] }, { "id": "PMID-1532661_T2", "type": "Protein", "text": [ "interleukin (IL) 4" ], "offsets": [ [ 244, 262 ] ], "normalized": [] }, { "id": "PMID-1532661_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 295, 299 ] ], "normalized": [] }, { "id": "PMID-1532661_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 516, 520 ] ], "normalized": [] }, { "id": "PMID-1532661_T5", "type": "Protein", "text": [ "granulocyte/macrophage colony-stimulating factor" ], "offsets": [ [ 600, 648 ] ], "normalized": [] }, { "id": "PMID-1532661_T6", "type": "Protein", "text": [ "granulocyte/macrophage colony-stimulating factor" ], "offsets": [ [ 741, 789 ] ], "normalized": [] }, { "id": "PMID-1532661_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 850, 854 ] ], "normalized": [] }, { "id": "PMID-1532661_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 972, 976 ] ], "normalized": [] }, { "id": "PMID-1532661_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1212, 1216 ] ], "normalized": [] }, { "id": "PMID-1532661_T10", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1594, 1598 ] ], "normalized": [] }, { "id": "PMID-1532661_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1695, 1699 ] ], "normalized": [] }, { "id": "PMID-1532661_T12", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1747, 1751 ] ], "normalized": [] }, { "id": "PMID-1532661_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1786, 1790 ] ], "normalized": [] }, { "id": "PMID-1532661_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1852, 1856 ] ], "normalized": [] }, { "id": "PMID-1532661_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1861, 1865 ] ], "normalized": [] }, { "id": "PMID-1532661_T19", "type": "Entity", "text": [ "P sequence" ], "offsets": [ [ 1194, 1204 ] ], "normalized": [] } ]

[ { "id": "PMID-1532661_E1", "type": "Positive_regulation", "trigger": { "text": [ "confers" ], "offsets": [ [ 177, 184 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_E2" } ] }, { "id": "PMID-1532661_E2", "type": "Regulation", "trigger": { "text": [ "responsiveness" ], "offsets": [ [ 185, 199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_T2" } ] }, { "id": "PMID-1532661_E3", "type": "Binding", "trigger": { "text": [ "recognize" ], "offsets": [ [ 1180, 1189 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_T9" }, { "role": "Site", "ref_id": "PMID-1532661_T19" } ] }, { "id": "PMID-1532661_E4", "type": "Positive_regulation", "trigger": { "text": [ "requirements" ], "offsets": [ [ 1577, 1589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_E5" } ] }, { "id": "PMID-1532661_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1599, 1609 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_T10" } ] }, { "id": "PMID-1532661_E6", "type": "Binding", "trigger": { "text": [ "recognize" ], "offsets": [ [ 1842, 1851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_T15" } ] }, { "id": "PMID-1532661_E7", "type": "Binding", "trigger": { "text": [ "recognize" ], "offsets": [ [ 1842, 1851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1532661_T14" } ] } ]

[]

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[ { "id": "PMID-1533884__text", "type": "abstract", "text": [ "Activation of the human immunodeficiency virus type 1 enhancer is not dependent on NFAT-1. \nThe function of a putative NFAT-1 site in the human immunodeficiency virus type 1 enhancer has been analyzed. Activation by the T-cell antigen receptor is minimal in Jurkat cells and is mediated by the kappa B sites. The putative NFAT-1 region is not required for the response to anti-CD3 or to mitogens in T-cell, B-cell, or monocyte/macrophage leukemia lines, nor is it a cis-acting negative regulatory element. " ], "offsets": [ [ 0, 506 ] ] } ]

[ { "id": "PMID-1533884_T1", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 83, 89 ] ], "normalized": [] }, { "id": "PMID-1533884_T2", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 119, 125 ] ], "normalized": [] }, { "id": "PMID-1533884_T3", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 322, 328 ] ], "normalized": [] } ]

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[ { "id": "PMID-1537389__text", "type": "abstract", "text": [ "Interleukin 6-induced differentiation of a human B cell line into IgM-secreting plasma cells is mediated by c-fos. \nThe role of the protooncogene c-fos in interleukin (IL) 6-induced B cell differentiation was assessed. Treatment of SKW 6.4 cells with IL 6 induced a transient and early stimulation of c-fos sense mRNA expression. The effect appeared within 30 min and returned to basal levels after 2 h. The addition of antisense oligonucleotides to c-fos significantly inhibited IL 6-induced IgM production by SKW 6.4 cells (p less than 0.001), whereas control oligonucleotides had no inhibitory effect. These results indicate that activation of c-fos is involved in IL 6-induced differentiation of SKW 6.4 cells into IgM-secreting cells. " ], "offsets": [ [ 0, 740 ] ] } ]

[ { "id": "PMID-1537389_T1", "type": "Protein", "text": [ "Interleukin 6" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-1537389_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 108, 113 ] ], "normalized": [] }, { "id": "PMID-1537389_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 146, 151 ] ], "normalized": [] }, { "id": "PMID-1537389_T4", "type": "Protein", "text": [ "interleukin (IL) 6" ], "offsets": [ [ 155, 173 ] ], "normalized": [] }, { "id": "PMID-1537389_T5", "type": "Protein", "text": [ "IL 6" ], "offsets": [ [ 251, 255 ] ], "normalized": [] }, { "id": "PMID-1537389_T6", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 301, 306 ] ], "normalized": [] }, { "id": "PMID-1537389_T7", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 450, 455 ] ], "normalized": [] }, { "id": "PMID-1537389_T8", "type": "Protein", "text": [ "IL 6" ], "offsets": [ [ 480, 484 ] ], "normalized": [] }, { "id": "PMID-1537389_T9", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 647, 652 ] ], "normalized": [] }, { "id": "PMID-1537389_T10", "type": "Protein", "text": [ "IL 6" ], "offsets": [ [ 668, 672 ] ], "normalized": [] } ]

[ { "id": "PMID-1537389_E1", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 286, 297 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537389_E2" } ] }, { "id": "PMID-1537389_E2", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 318, 328 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537389_T6" } ] }, { "id": "PMID-1537389_E3", "type": "Positive_regulation", "trigger": { "text": [ "appeared" ], "offsets": [ [ 341, 349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537389_E1" } ] }, { "id": "PMID-1537389_E4", "type": "Negative_regulation", "trigger": { "text": [ "returned" ], "offsets": [ [ 368, 376 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537389_E1" } ] }, { "id": "PMID-1537389_E5", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 633, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537389_T9" } ] } ]

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[ { "id": "PMID-1537556__text", "type": "abstract", "text": [ "Binding of erythroid and non-erythroid nuclear proteins to the silencer of the human epsilon-globin-encoding gene. \nTo clarify the molecular mechanisms involved in the developmental control of hemoglobin-encoding genes we have been studying the expression of these genes in human cells in continuous culture. We have previously reported the presence of a transcriptional control element with the properties of a silencer extending from -392 to -177 bp relative to the cap site of the human epsilon-globin-encoding gene [Cao et al., Proc.Natl.Acad.Sci.USA 86 (1989) 5306-5309]. We also showed that this silencer has stronger inhibitory activity in HeLa cells, as compared to K562 human erythroleukemia cells. Using deletion mutants and cis-cloned synthetic oligodeoxyribonucleotides in transient expression assays, nucleotide sequences responsible for this effect have now been further delimited to 44 bp located from -294 to -251 bp. Gel electrophoresis mobility shift assays and DNaseI footprinting assays demonstrate that these negative regulatory sequences are recognized differently by proteins present in nuclear extracts obtained from HeLa and K562 cells. Two binding proteins are detected in K562 nuclear extracts, while only one is found in extracts from HeLa cells. Possible mechanisms by which these proteins may regulate transcription of the epsilon-globin-encoding gene in erythroid and non-erythroid cells are discussed. " ], "offsets": [ [ 0, 1434 ] ] } ]

[ { "id": "PMID-1537556_T1", "type": "Protein", "text": [ "epsilon-globin" ], "offsets": [ [ 85, 99 ] ], "normalized": [] }, { "id": "PMID-1537556_T2", "type": "Protein", "text": [ "epsilon-globin" ], "offsets": [ [ 490, 504 ] ], "normalized": [] }, { "id": "PMID-1537556_T3", "type": "Protein", "text": [ "DNaseI" ], "offsets": [ [ 980, 986 ] ], "normalized": [] }, { "id": "PMID-1537556_T4", "type": "Protein", "text": [ "epsilon-globin" ], "offsets": [ [ 1353, 1367 ] ], "normalized": [] } ]

[ { "id": "PMID-1537556_E1", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 1323, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537556_E2" } ] }, { "id": "PMID-1537556_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1332, 1345 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1537556_T4" } ] } ]

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[ { "id": "PMID-1541828__text", "type": "abstract", "text": [ "T cell-specific negative regulation of transcription of the human cytokine IL-4. \nIL-4 secreted by activated T cells is a pleiotropic cytokine affecting growth and differentiation of diverse cell types such as T cells, B cells, and mast cells. We investigated the upstream regulatory elements of the human IL-4 promoter. A novel T cell-specific negative regulatory element (NRE) composed of two protein-binding sites were mapped in the 5' flanking region of the IL-4 gene: -311CTCCCTTCT-303 (NRE-I) and -288CTTTTTGCTT-TGC-300 (NRE-II). A T cell-specific protein Neg-1 and a ubiquitous protein Neg-2 binding to NRE-I and NRE-II, respectively, were identified. Furthermore, a positive regulatory element was found 45 bp downstream of the NRE. The enhancer activity of the PRE was completely suppressed when the NRE was present. These data suggest that IL-4 promoter activity is normally down-regulated by an NRE via repression of the enhancer positive regulatory element. These data may have implications for the stringent control of IL-4 expression in T cells. " ], "offsets": [ [ 0, 1060 ] ] } ]

[ { "id": "PMID-1541828_T1", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 75, 79 ] ], "normalized": [] }, { "id": "PMID-1541828_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 82, 86 ] ], "normalized": [] }, { "id": "PMID-1541828_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 306, 310 ] ], "normalized": [] }, { "id": "PMID-1541828_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 462, 466 ] ], "normalized": [] }, { "id": "PMID-1541828_T5", "type": "Protein", "text": [ "Neg-1" ], "offsets": [ [ 562, 567 ] ], "normalized": [] }, { "id": "PMID-1541828_T6", "type": "Protein", "text": [ "Neg-2" ], "offsets": [ [ 593, 598 ] ], "normalized": [] }, { "id": "PMID-1541828_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 850, 854 ] ], "normalized": [] }, { "id": "PMID-1541828_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1032, 1036 ] ], "normalized": [] }, { "id": "PMID-1541828_T13", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 855, 863 ] ], "normalized": [] } ]

[ { "id": "PMID-1541828_E1", "type": "Negative_regulation", "trigger": { "text": [ "negative regulation" ], "offsets": [ [ 16, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_E2" } ] }, { "id": "PMID-1541828_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 39, 52 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_T1" } ] }, { "id": "PMID-1541828_E3", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 87, 95 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_T2" } ] }, { "id": "PMID-1541828_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 599, 606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_T6" } ] }, { "id": "PMID-1541828_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 599, 606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_T5" } ] }, { "id": "PMID-1541828_E6", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 885, 899 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_T7" }, { "role": "Site", "ref_id": "PMID-1541828_T13" } ] }, { "id": "PMID-1541828_E7", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 1021, 1028 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_E8" } ] }, { "id": "PMID-1541828_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1037, 1047 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1541828_T8" } ] } ]

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[ { "id": "PMID-1545132__text", "type": "abstract", "text": [ "Human T cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor AP-1. \nThe induction of the AP-1 transcription factor has been ascribed to the early events leading to T cell differentiation and activation. We have studied the regulation of AP-1 activity in human peripheral blood T lymphocytes stimulated through the activation inducer molecule (AIM)/CD69 activation pathway. Phorbol esters are required to induce AIM/CD69 cell-surface expression as well as for triggering the proliferation of T cells in conjunction with anti-AIM mAb. Mobility shift assays showed that addition of anti-AIM mAb to PMA-treated T lymphocytes markedly enhanced the binding activity of AP-1 to its cognate sequence, the phorbol ester response element. In contrast, anti-AIM mAb did not induce any change in the binding activity of NF-kappa B, a transcription factor whose activity is also regulated by protein kinase C. The increase in AP-1-binding activity was accompanied by the marked stimulation of the transcription of c-fos but not that of c-jun. Blockade of the DNA-binding complexes with an anti-Fos mAb demonstrated a direct participation of c-Fos in the AP-1 complexes induced by anti-AIM mAb. Most of the AP-1 activity could be eliminated when the anti-AIM mAb was added to the culture medium in the presence of cycloheximide, suggesting that de novo protein synthesis is crucial for the induction of AP-1-binding activity. These data provide the evidence that activation of human peripheral blood T cells through the AIM activation pathway regulate the activity of AP-1. Therefore, this pathway appears as a crucial step in the initiation of early T cell activation events. " ], "offsets": [ [ 0, 1717 ] ] } ]

[ { "id": "PMID-1545132_T1", "type": "Protein", "text": [ "activation-inducer molecule" ], "offsets": [ [ 36, 63 ] ], "normalized": [] }, { "id": "PMID-1545132_T2", "type": "Protein", "text": [ "CD69" ], "offsets": [ [ 64, 68 ] ], "normalized": [] }, { "id": "PMID-1545132_T3", "type": "Protein", "text": [ "activation inducer molecule" ], "offsets": [ [ 368, 395 ] ], "normalized": [] }, { "id": "PMID-1545132_T4", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 397, 400 ] ], "normalized": [] }, { "id": "PMID-1545132_T5", "type": "Protein", "text": [ "CD69" ], "offsets": [ [ 402, 406 ] ], "normalized": [] }, { "id": "PMID-1545132_T6", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 465, 468 ] ], "normalized": [] }, { "id": "PMID-1545132_T7", "type": "Protein", "text": [ "CD69" ], "offsets": [ [ 469, 473 ] ], "normalized": [] }, { "id": "PMID-1545132_T8", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 578, 581 ] ], "normalized": [] }, { "id": "PMID-1545132_T9", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 638, 641 ] ], "normalized": [] }, { "id": "PMID-1545132_T10", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "PMID-1545132_T11", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1055, 1060 ] ], "normalized": [] }, { "id": "PMID-1545132_T12", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1077, 1082 ] ], "normalized": [] }, { "id": "PMID-1545132_T13", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 1135, 1138 ] ], "normalized": [] }, { "id": "PMID-1545132_T14", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1182, 1187 ] ], "normalized": [] }, { "id": "PMID-1545132_T15", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 1226, 1229 ] ], "normalized": [] }, { "id": "PMID-1545132_T16", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 1295, 1298 ] ], "normalized": [] }, { "id": "PMID-1545132_T17", "type": "Protein", "text": [ "AIM" ], "offsets": [ [ 1560, 1563 ] ], "normalized": [] }, { "id": "PMID-1545132_T19", "type": "Entity", "text": [ "cell-surface" ], "offsets": [ [ 474, 486 ] ], "normalized": [] } ]

[ { "id": "PMID-1545132_E1", "type": "Positive_regulation", "trigger": { "text": [ "required to induce" ], "offsets": [ [ 446, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_E2" } ] }, { "id": "PMID-1545132_E2", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 487, 497 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_T7" }, { "role": "AtLoc", "ref_id": "PMID-1545132_T19" } ] }, { "id": "PMID-1545132_E3", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1019, 1030 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_E6" } ] }, { "id": "PMID-1545132_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1019, 1030 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_E5" } ] }, { "id": "PMID-1545132_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1038, 1051 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_T11" } ] }, { "id": "PMID-1545132_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1038, 1051 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_T12" } ] }, { "id": "PMID-1545132_E7", "type": "Binding", "trigger": { "text": [ "participation" ], "offsets": [ [ 1165, 1178 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_T14" } ] }, { "id": "PMID-1545132_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1210, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1545132_E7" } ] } ]

[ { "id": "PMID-1545132_1", "entity_ids": [ "PMID-1545132_T3", "PMID-1545132_T4" ] }, { "id": "PMID-1545132_2", "entity_ids": [ "PMID-1545132_T7", "PMID-1545132_T6" ] }, { "id": "PMID-1545132_3", "entity_ids": [ "PMID-1545132_T1", "PMID-1545132_T2" ] } ]

[]

[ { "id": "PMID-1560002__text", "type": "abstract", "text": [ "The B cell-specific nuclear factor OTF-2 positively regulates transcription of the human class II transplantation gene, DRA. \nThe promoter of the major histocompatibility class II gene DRA contains an octamer element (ATTTGCAT) that is required for efficient DRA expression in B cells. Several DNA-binding proteins are known to bind this sequence. The best characterized are the B cell-specific OTF-2 and the ubiquitous OTF-1. This report directly demonstrates that OTF-2 but not OTF-1 regulates the DRA gene. In vitro transcription analysis using protein fractions enriched for the octamer-binding protein OTF-2 demonstrate a positive functional role for OTF-2 in DRA gene transcription. In contrast, OTF-1-enriched protein fractions did not affect DRA gene transcription although it functionally enhanced the transcription of another gene. Recombinant OTF-2 protein produced by in vitro transcription/translation could also enhance DRA gene transcription in vitro. In vivo transient transfection studies utilizing an OTF-2 expression vector resulted in similar findings: that OTF-2 protein enhanced DRA gene transcription, and that this effect requires an intact octamer element. Together these results constitute the first direct evidence of a positive role for the lymphoid-specific octamer-binding factor in DRA gene transcription. " ], "offsets": [ [ 0, 1337 ] ] } ]

[ { "id": "PMID-1560002_T1", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 35, 40 ] ], "normalized": [] }, { "id": "PMID-1560002_T2", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 120, 123 ] ], "normalized": [] }, { "id": "PMID-1560002_T3", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 185, 188 ] ], "normalized": [] }, { "id": "PMID-1560002_T4", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 259, 262 ] ], "normalized": [] }, { "id": "PMID-1560002_T5", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 395, 400 ] ], "normalized": [] }, { "id": "PMID-1560002_T6", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "PMID-1560002_T7", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 466, 471 ] ], "normalized": [] }, { "id": "PMID-1560002_T8", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 480, 485 ] ], "normalized": [] }, { "id": "PMID-1560002_T9", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 500, 503 ] ], "normalized": [] }, { "id": "PMID-1560002_T10", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 607, 612 ] ], "normalized": [] }, { "id": "PMID-1560002_T11", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 656, 661 ] ], "normalized": [] }, { "id": "PMID-1560002_T12", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 665, 668 ] ], "normalized": [] }, { "id": "PMID-1560002_T13", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 702, 707 ] ], "normalized": [] }, { "id": "PMID-1560002_T14", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 750, 753 ] ], "normalized": [] }, { "id": "PMID-1560002_T15", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 854, 859 ] ], "normalized": [] }, { "id": "PMID-1560002_T16", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 934, 937 ] ], "normalized": [] }, { "id": "PMID-1560002_T17", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1019, 1024 ] ], "normalized": [] }, { "id": "PMID-1560002_T18", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1078, 1083 ] ], "normalized": [] }, { "id": "PMID-1560002_T19", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 1101, 1104 ] ], "normalized": [] }, { "id": "PMID-1560002_T20", "type": "Protein", "text": [ "DRA" ], "offsets": [ [ 1313, 1316 ] ], "normalized": [] }, { "id": "PMID-1560002_T23", "type": "Entity", "text": [ "ATTTGCAT" ], "offsets": [ [ 218, 226 ] ], "normalized": [] } ]

[ { "id": "PMID-1560002_E1", "type": "Positive_regulation", "trigger": { "text": [ "positively regulates" ], "offsets": [ [ 41, 61 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E2" }, { "role": "Cause", "ref_id": "PMID-1560002_T1" } ] }, { "id": "PMID-1560002_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 62, 75 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T2" } ] }, { "id": "PMID-1560002_E3", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 236, 244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E4" }, { "role": "Cause", "ref_id": "PMID-1560002_T3" }, { "role": "CSite", "ref_id": "PMID-1560002_T23" } ] }, { "id": "PMID-1560002_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 263, 273 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T4" } ] }, { "id": "PMID-1560002_E5", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 328, 332 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T3" }, { "role": "Site", "ref_id": "PMID-1560002_T23" } ] }, { "id": "PMID-1560002_E6", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 486, 495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T9" }, { "role": "Cause", "ref_id": "PMID-1560002_T8" } ] }, { "id": "PMID-1560002_E7", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 486, 495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T9" }, { "role": "Cause", "ref_id": "PMID-1560002_T7" } ] }, { "id": "PMID-1560002_E8", "type": "Positive_regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 647, 651 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E9" }, { "role": "Cause", "ref_id": "PMID-1560002_T11" } ] }, { "id": "PMID-1560002_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 674, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T12" } ] }, { "id": "PMID-1560002_E10", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 743, 749 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E11" }, { "role": "Cause", "ref_id": "PMID-1560002_T13" } ] }, { "id": "PMID-1560002_E11", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 759, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T14" } ] }, { "id": "PMID-1560002_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 889, 902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T15" } ] }, { "id": "PMID-1560002_E13", "type": "Positive_regulation", "trigger": { "text": [ "enhance" ], "offsets": [ [ 926, 933 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E14" }, { "role": "Cause", "ref_id": "PMID-1560002_T15" } ] }, { "id": "PMID-1560002_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 943, 956 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T16" } ] }, { "id": "PMID-1560002_E15", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1092, 1100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E16" }, { "role": "Cause", "ref_id": "PMID-1560002_T18" } ] }, { "id": "PMID-1560002_E16", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1110, 1123 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T19" } ] }, { "id": "PMID-1560002_E17", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 1146, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E15" } ] }, { "id": "PMID-1560002_E18", "type": "Positive_regulation", "trigger": { "text": [ "positive role" ], "offsets": [ [ 1247, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_E19" } ] }, { "id": "PMID-1560002_E19", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1322, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1560002_T20" } ] } ]

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[ { "id": "PMID-1583734__text", "type": "abstract", "text": [ "Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription. \nNF-kappa B is a protein complex which functions in concert with the tat-I gene product to stimulate human immunodeficiency virus (HIV) transcription. To determine whether specific members of the NF-kappa B family contribute to this effect, we have examined the abilities of different NF-kappa B subunits to act with Tat-I to stimulate transcription of HIV in Jurkat T-leukemia cells. We have found that the p49(100) DNA binding subunit, together with p65, can act in concert with Tat-I to stimulate the expression of HIV-CAT plasmid. Little effect was observed with 50-kDa forms of p105 NF-kappa B or rel, in combination with p65 or full-length c-rel, which do not stimulate the HIV enhancer in these cells. These findings suggest that the combination of p49(100) and p65 NF-kappa B can act in concert with the tat-I gene product to stimulate the synthesis of HIV RNA. " ], "offsets": [ [ 0, 987 ] ] } ]

[ { "id": "PMID-1583734_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 49, 52 ] ], "normalized": [] }, { "id": "PMID-1583734_T2", "type": "Protein", "text": [ "tat-I" ], "offsets": [ [ 186, 191 ] ], "normalized": [] }, { "id": "PMID-1583734_T3", "type": "Protein", "text": [ "Tat-I" ], "offsets": [ [ 434, 439 ] ], "normalized": [] }, { "id": "PMID-1583734_T4", "type": "Protein", "text": [ "p49(100)" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "PMID-1583734_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 569, 572 ] ], "normalized": [] }, { "id": "PMID-1583734_T6", "type": "Protein", "text": [ "Tat-I" ], "offsets": [ [ 598, 603 ] ], "normalized": [] }, { "id": "PMID-1583734_T7", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 639, 642 ] ], "normalized": [] }, { "id": "PMID-1583734_T8", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 700, 704 ] ], "normalized": [] }, { "id": "PMID-1583734_T9", "type": "Protein", "text": [ "rel" ], "offsets": [ [ 719, 722 ] ], "normalized": [] }, { "id": "PMID-1583734_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 744, 747 ] ], "normalized": [] }, { "id": "PMID-1583734_T11", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 763, 768 ] ], "normalized": [] }, { "id": "PMID-1583734_T12", "type": "Protein", "text": [ "p49(100)" ], "offsets": [ [ 873, 881 ] ], "normalized": [] }, { "id": "PMID-1583734_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 886, 889 ] ], "normalized": [] }, { "id": "PMID-1583734_T14", "type": "Protein", "text": [ "tat-I" ], "offsets": [ [ 929, 934 ] ], "normalized": [] } ]

[ { "id": "PMID-1583734_E1", "type": "Binding", "trigger": { "text": [ "binding subunit" ], "offsets": [ [ 538, 553 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_T4" } ] }, { "id": "PMID-1583734_E2", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 607, 616 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_E3" } ] }, { "id": "PMID-1583734_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 621, 631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_T7" } ] }, { "id": "PMID-1583734_E4", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 659, 665 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_E3" }, { "role": "Cause", "ref_id": "PMID-1583734_T10" } ] }, { "id": "PMID-1583734_E5", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 659, 665 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_E3" }, { "role": "Cause", "ref_id": "PMID-1583734_T8" } ] }, { "id": "PMID-1583734_E6", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 659, 665 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_E3" }, { "role": "Cause", "ref_id": "PMID-1583734_T11" } ] }, { "id": "PMID-1583734_E7", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 659, 665 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1583734_E3" }, { "role": "Cause", "ref_id": "PMID-1583734_T9" } ] } ]

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[ { "id": "PMID-1618911__text", "type": "abstract", "text": [ "Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins. \nThe NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat. In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and heterodimer complexes in co-renaturation experiments. Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers. These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins. " ], "offsets": [ [ 0, 1178 ] ] } ]

[ { "id": "PMID-1618911_T1", "type": "Protein", "text": [ "rel" ], "offsets": [ [ 165, 168 ] ], "normalized": [] }, { "id": "PMID-1618911_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 964, 967 ] ], "normalized": [] } ]

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[ { "id": "PMID-1620119__text", "type": "abstract", "text": [ "Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity. \nPrevious cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif. Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however. We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line. Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells. This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2-mediated enhancer activation. Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation. Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position. The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position. " ], "offsets": [ [ 0, 1308 ] ] } ]

[ { "id": "PMID-1620119_T1", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-1620119_T2", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 218, 222 ] ], "normalized": [] }, { "id": "PMID-1620119_T3", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 290, 294 ] ], "normalized": [] }, { "id": "PMID-1620119_T4", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 422, 426 ] ], "normalized": [] }, { "id": "PMID-1620119_T5", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 592, 596 ] ], "normalized": [] }, { "id": "PMID-1620119_T6", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 818, 822 ] ], "normalized": [] }, { "id": "PMID-1620119_T7", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 834, 838 ] ], "normalized": [] }, { "id": "PMID-1620119_T8", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 934, 938 ] ], "normalized": [] }, { "id": "PMID-1620119_T9", "type": "Protein", "text": [ "Oct1" ], "offsets": [ [ 1045, 1049 ] ], "normalized": [] }, { "id": "PMID-1620119_T10", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 1201, 1205 ] ], "normalized": [] } ]

[ { "id": "PMID-1620119_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 159, 169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1620119_T2" } ] }, { "id": "PMID-1620119_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 295, 305 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1620119_T3" } ] }, { "id": "PMID-1620119_E3", "type": "Positive_regulation", "trigger": { "text": [ "generated" ], "offsets": [ [ 436, 445 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1620119_T4" } ] } ]

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

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

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[ { "id": "PMID-1645452__text", "type": "abstract", "text": [ "The human myelomonocytic cell line U-937 as a model for studying alterations in steroid-induced monokine gene expression: marked enhancement of lipopolysaccharide-stimulated interleukin-1 beta messenger RNA levels by 1,25-dihydroxyvitamin D3. \nThe active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is a potent regulator of human monocyte/macrophage function in vitro. To establish a model for 1,25-(OH)2D3 regulation of human monocyte monokine synthesis, three human cell lines (U-937, THP-1, and HL-60) were examined for: 1) the presence of functional 1,25-(OH)2D3 receptors; 2) the accumulation of interleukin-1 beta (IL-1 beta) mRNA and IL-1 beta protein in response to lipopolysaccharide (LPS); and 3) the regulation of this response by 1,25-(OH)2D3. All three cell lines expressed vitamin D receptor and had increased levels of IL-1 beta mRNA in response to LPS. Preincubation of cells with 1,25-(OH)2D3 augmented IL-1 beta mRNA levels only in U-937 and HL-60 cells. From these data, and taking into consideration their state of differentiation and relative ease of culture, U-937 was chosen over HL-60 and THP-1 as the cell line we further characterized. In U-937 cells, optimum time and dose of pretreatment with 1,25-(OH)2D3 were determined to be 12-24 h at a receptor saturating concentration of 1,25-(OH)2D3 (10 nM). Preincubation of cells with 1,25-(OH)2D3 had no effect on the time course of IL-1 beta mRNA appearance in response to LPS. However, exposure of U-937 cells to 1,25-(OH)2D3 increased by 200% the level of IL-1 beta mRNA detected and decreased by three orders of magnitude the concentration of LPS required to achieve steady state mRNA levels equivalent to those observed in U-937 cells not preincubated with the hormone.2+o " ], "offsets": [ [ 0, 1772 ] ] } ]

[ { "id": "PMID-1645452_T1", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 174, 192 ] ], "normalized": [] }, { "id": "PMID-1645452_T2", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 623, 641 ] ], "normalized": [] }, { "id": "PMID-1645452_T3", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 643, 652 ] ], "normalized": [] }, { "id": "PMID-1645452_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 663, 672 ] ], "normalized": [] }, { "id": "PMID-1645452_T5", "type": "Protein", "text": [ "vitamin D receptor" ], "offsets": [ [ 809, 827 ] ], "normalized": [] }, { "id": "PMID-1645452_T6", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 856, 865 ] ], "normalized": [] }, { "id": "PMID-1645452_T7", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 942, 951 ] ], "normalized": [] }, { "id": "PMID-1645452_T8", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1427, 1436 ] ], "normalized": [] }, { "id": "PMID-1645452_T9", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1553, 1562 ] ], "normalized": [] } ]

[ { "id": "PMID-1645452_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhancement" ], "offsets": [ [ 129, 140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_E2" } ] }, { "id": "PMID-1645452_E2", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_E3" } ] }, { "id": "PMID-1645452_E3", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 207, 213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T1" } ] }, { "id": "PMID-1645452_E4", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 607, 619 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T3" } ] }, { "id": "PMID-1645452_E5", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 607, 619 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T4" } ] }, { "id": "PMID-1645452_E6", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 733, 743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_E5" } ] }, { "id": "PMID-1645452_E7", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 733, 743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_E4" } ] }, { "id": "PMID-1645452_E8", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 799, 808 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T5" } ] }, { "id": "PMID-1645452_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 836, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T6" } ] }, { "id": "PMID-1645452_E10", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 932, 941 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T7" } ] }, { "id": "PMID-1645452_E11", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1398, 1404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_E13" } ] }, { "id": "PMID-1645452_E12", "type": "Transcription", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1442, 1452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T8" } ] }, { "id": "PMID-1645452_E13", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1453, 1467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_E12" } ] }, { "id": "PMID-1645452_E14", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1522, 1531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1645452_T9" } ] } ]

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[]

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

[]

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[]

[ { "id": "PMID-1653950__text", "type": "abstract", "text": [ "USF-related transcription factor, HIV-TF1, stimulates transcription of human immunodeficiency virus-1. \nThe transcription factor HIV-TF1, which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 (HIV-1), was purified from human B cells. HIV-TF1 had a molecular weight of 39,000. Binding of HIV-TF1 to the HIV long terminal repeat (LTR) activated transcription from the HIV promoter in vitro. The HIV-TF1-binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor (USF) in the adenovirus major late promoter. DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF. Interestingly, treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity, suggesting that phosphorylation of HIV-TF1 was essential for DNA binding. The disruption of HIV-TF1-binding site induced a 60% decrease in the level of transcription from the HIV promoter in vivo. These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1. " ], "offsets": [ [ 0, 1064 ] ] } ]

[ { "id": "PMID-1653950_T1", "type": "Protein", "text": [ "USF" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-1653950_T2", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 34, 41 ] ], "normalized": [] }, { "id": "PMID-1653950_T3", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 129, 136 ] ], "normalized": [] }, { "id": "PMID-1653950_T4", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 281, 288 ] ], "normalized": [] }, { "id": "PMID-1653950_T5", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 334, 341 ] ], "normalized": [] }, { "id": "PMID-1653950_T6", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 440, 447 ] ], "normalized": [] }, { "id": "PMID-1653950_T7", "type": "Protein", "text": [ "upstream stimulatory factor" ], "offsets": [ [ 510, 537 ] ], "normalized": [] }, { "id": "PMID-1653950_T8", "type": "Protein", "text": [ "USF" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "PMID-1653950_T9", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 609, 616 ] ], "normalized": [] }, { "id": "PMID-1653950_T10", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 632, 639 ] ], "normalized": [] }, { "id": "PMID-1653950_T11", "type": "Protein", "text": [ "USF" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "PMID-1653950_T12", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 715, 722 ] ], "normalized": [] }, { "id": "PMID-1653950_T13", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 815, 822 ] ], "normalized": [] }, { "id": "PMID-1653950_T14", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 872, 879 ] ], "normalized": [] }, { "id": "PMID-1653950_T15", "type": "Protein", "text": [ "HIV-TF1" ], "offsets": [ [ 1004, 1011 ] ], "normalized": [] } ]

[ { "id": "PMID-1653950_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 144, 149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T3" } ] }, { "id": "PMID-1653950_E2", "type": "Binding", "trigger": { "text": [ "Binding" ], "offsets": [ [ 323, 330 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T5" } ] }, { "id": "PMID-1653950_E3", "type": "Binding", "trigger": { "text": [ "recognized" ], "offsets": [ [ 496, 506 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T8" } ] }, { "id": "PMID-1653950_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 587, 594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T9" } ] }, { "id": "PMID-1653950_E5", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 746, 753 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_E6" } ] }, { "id": "PMID-1653950_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 762, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T12" } ] }, { "id": "PMID-1653950_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 796, 811 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T13" } ] }, { "id": "PMID-1653950_E8", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 827, 836 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_E9" }, { "role": "Cause", "ref_id": "PMID-1653950_E7" } ] }, { "id": "PMID-1653950_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 845, 852 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1653950_T13" } ] } ]

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[ { "id": "PMID-1655897__text", "type": "abstract", "text": [ "Nuclear transcription factors that bind to elements of the IL-2 promoter. Induction requirements in primary human T cells. \nPrior studies have identified several elements that contribute to the activity of the IL-2 promoter in the stimulated T cell line, Jurkat. The sites and their corresponding nuclear binding factors include: NF-kappa B, AP-1, AP-3, OCT-1, and NF-AT. The latter \"nuclear factor for activated T cells\" likely contributes to the tissue specificity of IL-2 gene expression. Using electrophoretic mobility shift assays, we have studied these transcription factors in primary T cells from human blood to verify their presence in a physiologic setting and to identify the signals that stimulate factor activity. All factors are induced in the nuclei of T cells upon activation with mitogens but not with exogenous IL-2 growth factor. However, the signaling requirements and sensitivity to protein synthesis inhibitors differ considerably. Only the activities for NF-AT and AP-1 sites require two signals for optimal induction, i.e., PMA plus either lectin or antibody to the CD3 or CD28 surface molecules. Other factors are induced by lectin, antibody, and/or PMA alone. After appropriate stimulation, both NF-AT and AP-1 are peculiarly sensitive to the protein synthesis inhibitor anisomycin. Our data correlate the activity of NF-AT and AP-1 in gel shift assays with the two signals requirements for IL-2 gene expression. " ], "offsets": [ [ 0, 1439 ] ] } ]

[ { "id": "PMID-1655897_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 59, 63 ] ], "normalized": [] }, { "id": "PMID-1655897_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 210, 214 ] ], "normalized": [] }, { "id": "PMID-1655897_T3", "type": "Protein", "text": [ "OCT-1" ], "offsets": [ [ 354, 359 ] ], "normalized": [] }, { "id": "PMID-1655897_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 470, 474 ] ], "normalized": [] }, { "id": "PMID-1655897_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 829, 833 ] ], "normalized": [] }, { "id": "PMID-1655897_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1097, 1101 ] ], "normalized": [] }, { "id": "PMID-1655897_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1417, 1421 ] ], "normalized": [] }, { "id": "PMID-1655897_T9", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 64, 72 ] ], "normalized": [] }, { "id": "PMID-1655897_T11", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 215, 223 ] ], "normalized": [] } ]

[ { "id": "PMID-1655897_E1", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 35, 39 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T1" }, { "role": "Site", "ref_id": "PMID-1655897_T9" } ] }, { "id": "PMID-1655897_E2", "type": "Regulation", "trigger": { "text": [ "contribute" ], "offsets": [ [ 176, 186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T2" }, { "role": "Site", "ref_id": "PMID-1655897_T11" } ] }, { "id": "PMID-1655897_E3", "type": "Regulation", "trigger": { "text": [ "contributes" ], "offsets": [ [ 429, 440 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_E4" } ] }, { "id": "PMID-1655897_E4", "type": "Regulation", "trigger": { "text": [ "specificity" ], "offsets": [ [ 455, 466 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_E5" } ] }, { "id": "PMID-1655897_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 480, 490 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T4" } ] }, { "id": "PMID-1655897_E6", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 700, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T3" } ] }, { "id": "PMID-1655897_E7", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 743, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T3" } ] }, { "id": "PMID-1655897_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 743, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T3" }, { "role": "Cause", "ref_id": "PMID-1655897_T5" } ] }, { "id": "PMID-1655897_E9", "type": "Positive_regulation", "trigger": { "text": [ "requirements" ], "offsets": [ [ 872, 884 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T3" } ] }, { "id": "PMID-1655897_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1139, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T3" } ] }, { "id": "PMID-1655897_E11", "type": "Positive_regulation", "trigger": { "text": [ "requirements" ], "offsets": [ [ 1400, 1412 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_E12" } ] }, { "id": "PMID-1655897_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1427, 1437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655897_T7" } ] } ]

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[]

[ { "id": "PMID-1656391__text", "type": "abstract", "text": [ "An erythroid specific enhancer upstream to the gene encoding the cell-type specific transcription factor GATA-1. \nThe transcription factor GATA-1 is expressed in a subset of hemopoietic cells, where it mediates the cell-type specific expression of several genes. We have cloned the mouse and human GATA-1 genes. A region upstream to the first exon, and highly conserved between mouse and man, acts as an erythroid specific enhancer in transient assays, if linked to the GATA-1 or to the SV40 promoter. The activity of the enhancer is almost completely dependent on the integrity of a dimeric GATA-1 binding site. " ], "offsets": [ [ 0, 613 ] ] } ]

[ { "id": "PMID-1656391_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "PMID-1656391_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 139, 145 ] ], "normalized": [] }, { "id": "PMID-1656391_T3", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 470, 476 ] ], "normalized": [] }, { "id": "PMID-1656391_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 592, 598 ] ], "normalized": [] } ]

[ { "id": "PMID-1656391_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 149, 158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1656391_T2" } ] } ]

[]

[]

[ { "id": "PMID-1658795__text", "type": "abstract", "text": [ "Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains. \nWe report the structure and regulation of a gene represented by clone pAT 133, which is induced upon transition from a resting state (G0) through the early phase of the cell cycle (G1). The pAT 133 gene is immediately induced, with FOS-like kinetics, in human T cells and in fibroblasts. Primary structure analysis showed that the encoded protein contains three tandem zinc-finger sequences of the type Cys2-Xaa12-His2. This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2. Except for the conserved zinc-finger domains, the amino acid sequences of the three proteins are distinct. This structural similarity suggests that the pAT 133 gene encodes a transcription factor with a specific biological function. Comparing the regulation of these related zinc-finger-encoding genes showed coordinate induction upon mitogenic stimulation of resting T lymphocytes and of resting fibroblasts. However, upon transition from a proliferating (G1) to a resting state of the cell cycle the three genes were differently regulated. In human histiocytic U937 cells mRNA of clone pAT 133 was constitutively expressed, whereas mRNA of pAT 225/EGR1 was induced upon induction of terminal differentiation. In contrast mRNA representing pAT 591/EGR2 was not expressed in these cells. This difference in gene regulation suggests distinct biological roles in the control of cell proliferation for the respective proteins. " ], "offsets": [ [ 0, 1716 ] ] } ]

[ { "id": "PMID-1658795_T1", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 769, 773 ] ], "normalized": [] }, { "id": "PMID-1658795_T2", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 786, 790 ] ], "normalized": [] }, { "id": "PMID-1658795_T3", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 1442, 1446 ] ], "normalized": [] }, { "id": "PMID-1658795_T4", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 1541, 1545 ] ], "normalized": [] } ]

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[ { "id": "PMID-1668145__text", "type": "abstract", "text": [ "Every enhancer works with every promoter for all the combinations tested: could new regulatory pathways evolve by enhancer shuffling? \nThe promoters and enhancers of cell type-specific genes are often conserved in evolution, and hence one might expect that a given enhancer has evolved to work best with its own promoter. While this expectation may be realized in some cases, we have not found evidence for it. A total of 27 combinations of different promoters and enhancers were tested by transfection into cultured cells. We found that the relative efficiency of the enhancers is approximately the same, irrespective of the type of promoter used, i.e., there was no strong preference for any given enhancer/promoter combination. Notably, we do not see particularly strong transcription when the immunoglobulin kappa enhancer (or the immunoglobulin heavy chain enhancer) is used to activate a kappa gene promoter. We propose that a generally permissive enhancer/promoter interaction is of evolutionary benefit for higher eukaryotes: by enhancer shuffling, genes could be easily brought under a new type of inducibility/cell type specificity. " ], "offsets": [ [ 0, 1143 ] ] } ]

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[ { "id": "PMID-1676267__text", "type": "abstract", "text": [ "Towards a molecular understanding of T-cell differentiation. \nLymphoid differentiation is one of the best studied examples of mammalian development. Here Hans Clevers and Michael Owen describe how the cloning of the genes that encode T-cell-specific membrane proteins allows the identification of transcription factors that control the expression of these T-cell genes. Such transcription factors play a key role in the development of the mature T-cell phenotype by functioning as 'master regulators of T-cell differentiation'. " ], "offsets": [ [ 0, 528 ] ] } ]

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[ { "id": "PMID-1765275__text", "type": "abstract", "text": [ "Transcription factor requirements for U2 snRNA-encoding gene activation in B lymphoid cells. \nTranscription of a human U2 small nuclear RNA(snRNA)-encoding gene in HeLa cells requires a distal enhancer element, which is composed of one octamer motif (Oct) and three Sp 1-binding sites. To study the transcription factor requirement in B-cells, different U2 enhancer constructions were transfected into the lymphoid cell line, BJA-B. The results showed that the activation of U2 snRNA transcription in B-cells also requires an enhancer comprising both the Oct and at least one Sp 1-binding site. Deletion of all the Sp 1-binding sites from the enhancer reduces transcription by 80-90% in HeLa, as well as in BJA-B cells, whereas the removal of the octamer-binding site reduces transcription to levels below detection in both cell types. Enhancers containing a single Oct have, nevertheless, the capacity to partially activate U2 snRNA transcription in both HeLa cells, in which only OTF-1 is expressed, and in BJA-B cells in which OTF-2 is the predominantly expressed octamer-binding factor. The most likely interpretation of our results is that both the ubiquitous transcription factor, OTF-1, and the B-cell-specific transcription factor, OTF-2, can activate U2 snRNA transcription. The results also revealed a similar functional cooperation between the transcription factors which bind to the Oct and the adjacent Sp 1-binding site in BJA-B cells, as has been observed in HeLa cells, since a template which contains a weak binding site for OTFs expresses wild-type levels of U2 snRNA in both cell types when the weak octamer-binding site is combined with a Sp 1-binding site. " ], "offsets": [ [ 0, 1678 ] ] } ]

[ { "id": "PMID-1765275_T1", "type": "Protein", "text": [ "Sp 1" ], "offsets": [ [ 266, 270 ] ], "normalized": [] }, { "id": "PMID-1765275_T2", "type": "Protein", "text": [ "Sp 1" ], "offsets": [ [ 615, 619 ] ], "normalized": [] }, { "id": "PMID-1765275_T3", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 982, 987 ] ], "normalized": [] }, { "id": "PMID-1765275_T4", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "PMID-1765275_T5", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 1187, 1192 ] ], "normalized": [] }, { "id": "PMID-1765275_T6", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1240, 1245 ] ], "normalized": [] }, { "id": "PMID-1765275_T7", "type": "Protein", "text": [ "Sp 1" ], "offsets": [ [ 1416, 1420 ] ], "normalized": [] }, { "id": "PMID-1765275_T8", "type": "Protein", "text": [ "Sp 1" ], "offsets": [ [ 1659, 1663 ] ], "normalized": [] } ]

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[ { "id": "PMID-1768652__text", "type": "abstract", "text": [ "Kappa B-specific DNA binding proteins are differentially inhibited by enhancer mutations and biological oxidation. \nKappa B (kappa B) enhancer binding proteins isolated from the nuclei of activated human T cells produce two distinct nucleoprotein complexes when incubated with the kappa B element from the interleukin-2 receptor-alpha (IL-2R alpha) gene. These two DNA-protein complexes are composed of at least four host proteins (p50, p55, p75, p85), each of which shares structural similarity with the v-rel oncogene product. Nuclear expression of these proteins is induced with distinctly biphasic kinetics following phorbol ester activation of T cells (p55/p75 early and p50/p85 late). DNA-protein crosslinking studies have revealed that the more rapidly migrating B2 complex contains both p50 and p55 while the more slowly migrating B1 complex is composed of p50, p55, p75, and p85. Site-directed mutagenesis of the wild-type IL-2R alpha kappa B enhancer (GGGGAATCTCCC) has revealed that the binding of p50 and p55 (B2 complex) is particularly sensitive to alteration of the 5' triplet of deoxyguanosine residues. In contrast, formation of the B1 complex, reflecting the binding of p75 and p85, critically depends upon the more 3' sequences of this enhancer element. DNA binding by all four of these Rel-related factors is blocked by selective chemical modification of lysine and arginine residues, suggesting that both of these basic amino acids are required for binding to the kappa B element. Similarly, covalent modification of free sulfhydryl groups with diamide (reversible) or N-ethylmaleimide (irreversible) results in a complete loss of DNA binding activity. In contrast, mild oxidation with glucose oxidase selectively inhibits p75 and p85 binding while not blocking p50 and p55 interactions. These findings suggest that reduced cysteine thiols play an important role in the DNA binding activity of this family of Rel-related transcription factors. " ], "offsets": [ [ 0, 1965 ] ] } ]

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[ { "id": "PMID-1768652_1", "entity_ids": [ "PMID-1768652_T1", "PMID-1768652_T2" ] } ]

[]

[ { "id": "PMID-1777483__text", "type": "abstract", "text": [ "Activity of the kappa B enhancer of the interleukin-2 receptor alpha chain in somatic cell hybrids is accompanied by the nuclear localization of NF-kappa B. \nThe two nuclear proteins NF-kappa B (consisting of subunits p50 and p65) and the DNA-binding subunit of NF-kappa B (p50) by itself, also called KBF1, are constitutively expressed and localized in the nucleus of the human T-cell line IARC 301.5. In order to define the roles of these two factors, which bind to the same kappa B enhancers, in transcription activation we have prepared somatic cell hybrids between IARC 301.5 and a murine myeloma. Most hybrids express both KBF1 and NF-kappa B in their nuclei, but one hybrid expresses only KBF1. The kappa B enhancer of the gene encoding the interleukin-2 (IL-2) receptor alpha chain (IL-2R alpha) is functional only in the hybrids expressing nuclear NF-kappa B. These findings show that nuclear NF-kappa B is necessary to activate the kappa B enhancer, while KBF1 by itself is not sufficient. We propose that KBF1 is a competitive inhibitor of NF-kappa B and discuss how these factors may be involved in the transient expression of IL-2 and IL-2R alpha genes during the immune response. " ], "offsets": [ [ 0, 1194 ] ] } ]

[ { "id": "PMID-1777483_T1", "type": "Protein", "text": [ "interleukin-2 receptor alpha" ], "offsets": [ [ 40, 68 ] ], "normalized": [] }, { "id": "PMID-1777483_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 218, 221 ] ], "normalized": [] }, { "id": "PMID-1777483_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 226, 229 ] ], "normalized": [] }, { "id": "PMID-1777483_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 274, 277 ] ], "normalized": [] }, { "id": "PMID-1777483_T5", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 302, 306 ] ], "normalized": [] }, { "id": "PMID-1777483_T6", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 629, 633 ] ], "normalized": [] }, { "id": "PMID-1777483_T7", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 696, 700 ] ], "normalized": [] }, { "id": "PMID-1777483_T8", "type": "Protein", "text": [ "interleukin-2 (IL-2) receptor alpha chain" ], "offsets": [ [ 748, 789 ] ], "normalized": [] }, { "id": "PMID-1777483_T9", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 791, 802 ] ], "normalized": [] }, { "id": "PMID-1777483_T10", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 966, 970 ] ], "normalized": [] }, { "id": "PMID-1777483_T11", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 1016, 1020 ] ], "normalized": [] }, { "id": "PMID-1777483_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1139, 1143 ] ], "normalized": [] }, { "id": "PMID-1777483_T13", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 1148, 1159 ] ], "normalized": [] }, { "id": "PMID-1777483_T16", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 358, 365 ] ], "normalized": [] } ]

[ { "id": "PMID-1777483_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 327, 336 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T4" } ] }, { "id": "PMID-1777483_E2", "type": "Localization", "trigger": { "text": [ "localized" ], "offsets": [ [ 341, 350 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T4" }, { "role": "AtLoc", "ref_id": "PMID-1777483_T16" } ] }, { "id": "PMID-1777483_E3", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 460, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T4" } ] }, { "id": "PMID-1777483_E4", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 616, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T6" } ] }, { "id": "PMID-1777483_E5", "type": "Gene_expression", "trigger": { "text": [ "expresses" ], "offsets": [ [ 681, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T7" } ] }, { "id": "PMID-1777483_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1125, 1135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T13" } ] }, { "id": "PMID-1777483_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1125, 1135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1777483_T12" } ] } ]

[ { "id": "PMID-1777483_1", "entity_ids": [ "PMID-1777483_T8", "PMID-1777483_T9" ] } ]

[]

[ { "id": "PMID-1782151__text", "type": "abstract", "text": [ "Stimulation of interferon beta gene transcription in vitro by purified NF-kappa B and a novel TH protein. \nThe human interferon beta (IFN-beta) regulatory element consists of multiple enhanson domains which are targets for transcription factors involved in inducible expression of the promoter. To further characterize the protein-DNA interactions mediating IFN-beta induction, positive regulatory domain (PRD) II binding proteins were purified from phorbol ester induced Jurkat T-cells and from IFN primed, cycloheximide/polyinosinic-polycytidylic acid treated HeLa S3 cells. From HeLa cells, two major proteins of 52 and 45 kilodaltons (kD) copurified with DNA binding activity, whereas from T-cells, four proteins--a major protein of 52 kD and three minor proteins of 82, 67, and 43-47 kD--were purified. Also, an induction specific DNA binding protein was purified from HeLa cells that interacted with the (AAGTGA)4 tetrahexamer sequence and the PRDI domain. This protein is immunologically distinct from IRF-1/ISGF2. Uninduced or Sendai virus induced HeLa extracts were used to examine transcription in vitro using a series of IFN beta promoter deletions. Deletions upstream of the PRDII element increased transcription in the uninduced extract, indicating predominantly negative regulation of the promoter. A 2-4-fold increase in IFN-beta promoter transcription was observed in Sendai virus induced extracts, and deletion of PRDI and PRDII elements decreased this induced level of transcription. When purified PRDII and tetrahexamer binding proteins were added to the induced extract, a 4-fold increase in transcription was observed. These experiments demonstrate that it is possible to modulate IFN-beta transcription in vitro but indicate that additional proteins may be required to fully activate IFN-beta transcription. " ], "offsets": [ [ 0, 1830 ] ] } ]

[ { "id": "PMID-1782151_T1", "type": "Protein", "text": [ "interferon beta" ], "offsets": [ [ 15, 30 ] ], "normalized": [] }, { "id": "PMID-1782151_T2", "type": "Protein", "text": [ "interferon beta" ], "offsets": [ [ 117, 132 ] ], "normalized": [] }, { "id": "PMID-1782151_T3", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 134, 142 ] ], "normalized": [] }, { "id": "PMID-1782151_T4", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 358, 366 ] ], "normalized": [] }, { "id": "PMID-1782151_T5", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1009, 1014 ] ], "normalized": [] }, { "id": "PMID-1782151_T6", "type": "Protein", "text": [ "ISGF2" ], "offsets": [ [ 1015, 1020 ] ], "normalized": [] }, { "id": "PMID-1782151_T7", "type": "Protein", "text": [ "IFN beta" ], "offsets": [ [ 1132, 1140 ] ], "normalized": [] }, { "id": "PMID-1782151_T8", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 1336, 1344 ] ], "normalized": [] }, { "id": "PMID-1782151_T9", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 1702, 1710 ] ], "normalized": [] }, { "id": "PMID-1782151_T10", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 1806, 1814 ] ], "normalized": [] }, { "id": "PMID-1782151_T13", "type": "Entity", "text": [ "enhanson domains" ], "offsets": [ [ 184, 200 ] ], "normalized": [] } ]

[ { "id": "PMID-1782151_E1", "type": "Positive_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E2" } ] }, { "id": "PMID-1782151_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 36, 49 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_T1" } ] }, { "id": "PMID-1782151_E3", "type": "Regulation", "trigger": { "text": [ "targets" ], "offsets": [ [ 211, 218 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_T3" }, { "role": "Site", "ref_id": "PMID-1782151_T13" } ] }, { "id": "PMID-1782151_E4", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 257, 266 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E5" } ] }, { "id": "PMID-1782151_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 267, 277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_T3" } ] }, { "id": "PMID-1782151_E6", "type": "Positive_regulation", "trigger": { "text": [ "mediating" ], "offsets": [ [ 348, 357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E7" } ] }, { "id": "PMID-1782151_E7", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 367, 376 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_T4" } ] }, { "id": "PMID-1782151_E8", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1201, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E2" } ] }, { "id": "PMID-1782151_E9", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1324, 1332 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E10" } ] }, { "id": "PMID-1782151_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1354, 1367 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_T8" } ] }, { "id": "PMID-1782151_E11", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1455, 1464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E9" } ] }, { "id": "PMID-1782151_E12", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1600, 1608 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E10" } ] }, { "id": "PMID-1782151_E13", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1797, 1805 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_E14" } ] }, { "id": "PMID-1782151_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1815, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1782151_T10" } ] } ]

[ { "id": "PMID-1782151_1", "entity_ids": [ "PMID-1782151_T3", "PMID-1782151_T2" ] } ]

[]

[ { "id": "PMID-1829648__text", "type": "abstract", "text": [ "Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. \nWe have cloned a group of cDNAs representing mRNAs that are rapidly induced following adherence of human monocytes. One of the induced transcripts (MAD-3) encodes a protein of 317 amino acids with one domain containing five tandem repeats of the cdc10/ankyrin motif, which is 60% similar (46% identical) to the ankyrin repeat region of the precursor of NF-kappa B/KBF1 p50. The C-terminus has a putative protein kinase C phosphorylation site. In vitro translated MAD-3 protein was found to specifically inhibit the DNA-binding activity of the p50/p65 NF-kappa B complex but not that of the p50/p50 KBF1 factor or of other DNA-binding proteins. The MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation. " ], "offsets": [ [ 0, 956 ] ] } ]

[ { "id": "PMID-1829648_T1", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 261, 266 ] ], "normalized": [] }, { "id": "PMID-1829648_T2", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 477, 481 ] ], "normalized": [] }, { "id": "PMID-1829648_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 482, 485 ] ], "normalized": [] }, { "id": "PMID-1829648_T4", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 576, 581 ] ], "normalized": [] }, { "id": "PMID-1829648_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 656, 659 ] ], "normalized": [] }, { "id": "PMID-1829648_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 660, 663 ] ], "normalized": [] }, { "id": "PMID-1829648_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 703, 706 ] ], "normalized": [] }, { "id": "PMID-1829648_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 707, 710 ] ], "normalized": [] }, { "id": "PMID-1829648_T9", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 711, 715 ] ], "normalized": [] }, { "id": "PMID-1829648_T10", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 761, 766 ] ], "normalized": [] } ]

[ { "id": "PMID-1829648_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 240, 247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_T1" } ] }, { "id": "PMID-1829648_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 616, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_E6" } ] }, { "id": "PMID-1829648_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 616, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_E5" } ] }, { "id": "PMID-1829648_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 616, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_E7" } ] }, { "id": "PMID-1829648_E5", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 632, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_T6" } ] }, { "id": "PMID-1829648_E6", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 632, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_T7" } ] }, { "id": "PMID-1829648_E7", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 632, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1829648_T5" } ] } ]

[ { "id": "PMID-1829648_1", "entity_ids": [ "PMID-1829648_T7", "PMID-1829648_T8", "PMID-1829648_T9" ] }, { "id": "PMID-1829648_2", "entity_ids": [ "PMID-1829648_T2", "PMID-1829648_T3" ] } ]

[]

[ { "id": "PMID-1847170__text", "type": "abstract", "text": [ "Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line. \nPlatelet-activating factor is a potent mediator of the inflammatory response. Studies of the actions of platelet-activating factor have centered mainly around neutrophils, monocytes, and platelets. In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes. Employing the EBV-transformed human B cell line SKW6.4, we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine, phosphatidylinositol, and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M. The inactive precursor, lyso-platelet-activating factor, at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids. We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels, whereas lyso-platelet-activating factor was again ineffective. We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production. Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun. Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2. In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line. " ], "offsets": [ [ 0, 1920 ] ] } ]

[ { "id": "PMID-1847170_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1499, 1504 ] ], "normalized": [] }, { "id": "PMID-1847170_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1509, 1514 ] ], "normalized": [] }, { "id": "PMID-1847170_T3", "type": "Protein", "text": [ "5-lipoxygenase" ], "offsets": [ [ 1664, 1678 ] ], "normalized": [] }, { "id": "PMID-1847170_T4", "type": "Protein", "text": [ "phospholipase A2" ], "offsets": [ [ 1789, 1805 ] ], "normalized": [] } ]

[ { "id": "PMID-1847170_E1", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1445, 1453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1847170_E3" } ] }, { "id": "PMID-1847170_E2", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1445, 1453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1847170_E4" } ] }, { "id": "PMID-1847170_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1454, 1467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1847170_T1" } ] }, { "id": "PMID-1847170_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1454, 1467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1847170_T2" } ] } ]

[]

[]

[ { "id": "PMID-1851743__text", "type": "abstract", "text": [ "Inhibition of protein phosphatases by okadaic acid induces AP1 in human T cells. \nTo examine the role of protein phosphatases in T cell activation, Jurkat cells were treated with okadaic acid, an inhibitor of type 1 and 2A phosphatases, and nuclear extracts were examined for the presence of AP1 as a measure of early T cell activation. Okadaic acid was found to be a potent inducer of AP1. In contrast to phorbol esters such as phorbol myristate acetate (PMA), the induction of AP1 by okadaic acid occurs predominantly by transcriptional activation of the jun and fos family of proto-oncogenes. Surprisingly, while the addition of phytohemagglutinin further enhanced the induction of AP1, the addition of PMA inhibited it. Okadaic acid treatment was found to dramatically increase mRNA transcripts of the jun family of proto-oncogenes including c-jun, junD, and junB and to a lesser extent the fos family including c-fos and fra-1. By comparison, PMA is a very inefficient inducer of the jun gene family in Jurkat cells. Similar to its effect on the induction of AP1 by okadaic acid, PMA inhibits the induction of c-jun mRNA by okadaic acid. Transfection of c-jun promoter constructs confirmed the marked difference between PMA and okadaic acid in inducing c-jun transcription. The induction of AP1 by okadaic acid suggests that protein phosphatases 1 and 2A (PP1 and PP2A) may be involved in T cell activation as important negative regulators of the transcription factor AP1. " ], "offsets": [ [ 0, 1478 ] ] } ]

[ { "id": "PMID-1851743_T1", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 632, 650 ] ], "normalized": [] }, { "id": "PMID-1851743_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 846, 851 ] ], "normalized": [] }, { "id": "PMID-1851743_T3", "type": "Protein", "text": [ "junD" ], "offsets": [ [ 853, 857 ] ], "normalized": [] }, { "id": "PMID-1851743_T4", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 863, 867 ] ], "normalized": [] }, { "id": "PMID-1851743_T5", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 916, 921 ] ], "normalized": [] }, { "id": "PMID-1851743_T6", "type": "Protein", "text": [ "fra-1" ], "offsets": [ [ 926, 931 ] ], "normalized": [] }, { "id": "PMID-1851743_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1115, 1120 ] ], "normalized": [] }, { "id": "PMID-1851743_T8", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1159, 1164 ] ], "normalized": [] }, { "id": "PMID-1851743_T9", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1258, 1263 ] ], "normalized": [] }, { "id": "PMID-1851743_T10", "type": "Protein", "text": [ "protein phosphatases 1" ], "offsets": [ [ 1330, 1352 ] ], "normalized": [] }, { "id": "PMID-1851743_T11", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 1357, 1359 ] ], "normalized": [] } ]

[ { "id": "PMID-1851743_E1", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 773, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E7" } ] }, { "id": "PMID-1851743_E2", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 773, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E8" } ] }, { "id": "PMID-1851743_E3", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 773, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E10" } ] }, { "id": "PMID-1851743_E4", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 773, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E9" } ] }, { "id": "PMID-1851743_E5", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 773, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E6" } ] }, { "id": "PMID-1851743_E6", "type": "Transcription", "trigger": { "text": [ "mRNA transcripts" ], "offsets": [ [ 782, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T6" } ] }, { "id": "PMID-1851743_E7", "type": "Transcription", "trigger": { "text": [ "mRNA transcripts" ], "offsets": [ [ 782, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T3" } ] }, { "id": "PMID-1851743_E8", "type": "Transcription", "trigger": { "text": [ "mRNA transcripts" ], "offsets": [ [ 782, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T2" } ] }, { "id": "PMID-1851743_E9", "type": "Transcription", "trigger": { "text": [ "mRNA transcripts" ], "offsets": [ [ 782, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T4" } ] }, { "id": "PMID-1851743_E10", "type": "Transcription", "trigger": { "text": [ "mRNA transcripts" ], "offsets": [ [ 782, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T5" } ] }, { "id": "PMID-1851743_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1089, 1097 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E12" } ] }, { "id": "PMID-1851743_E12", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1102, 1111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T7" } ] }, { "id": "PMID-1851743_E13", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1249, 1257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_E14" } ] }, { "id": "PMID-1851743_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1264, 1277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1851743_T9" } ] } ]

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[ { "id": "PMID-1851861__text", "type": "abstract", "text": [ "Transactivation of the human immunodeficiency virus promoter by human herpesvirus 6 (HHV-6) strains GS and Z-29 in primary human T lymphocytes and identification of transactivating HHV-6(GS) gene fragments. \nHuman herpesvirus 6 (HHV-6) can activate the human immunodeficiency virus (HIV) promoter and accelerate cytopathic effects in HIV-infected human T cells. This study examines the regions of the HIV promoter required for HHV-6 transactivation in a heterogeneous population of primary human T lymphocytes with or without antigenic stimulation. Two different strains of HHV-6, GS and Z29, transactivated the HIV promoter. The GS strain transactivated the promoter in both stimulated and resting T cells, while the Z29 strain increased HIV promoter activity only in stimulated T cells. Three DNA clones containing HHV-6(GS) genomic fragments transactivated the HIV promoter in cotransfected T cells. A 21.4-kb DNA clone, pZVB70, showed the highest transactivating ability, while two other DNA fragments, pZVB10 (6.2 kb) and pZVH14 (8.7 kb), showed lower activity. One of these clones, pZVH14, activated the HIV promoter construct containing a mutation in the NF kappa B site. However, this mutated NF kappa B promoter was not transactivated during HHV-6(GS) infection or after cotransfection with pZVB70 or pZVB10. These data indicate that the NF kappa B sites of the HIV promoter are essential for its transactivation during HHV-6(GS) infection. By increasing HIV promoter activity in primary T lymphocytes, HHV-6 may consequently increase HIV replication, leading to an increase in the cytopathic effect on coinfected human T cells. " ], "offsets": [ [ 0, 1638 ] ] } ]

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[ { "id": "PMID-1883525__text", "type": "abstract", "text": [ "Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B. \nMacrophage-colony-stimulating factor (M-CSF), also referred to as CSF-1, regulates the survival, growth, differentiation and functional activity of monocytes by binding to a single class of high-affinity cell surface receptors, known to be the product of the c-fms protooncogene. The detection of both M-CSF and c-fms expression by cells of the monocyte lineage has suggested that M-CSF may act by an autocrine mechanism. Interestingly, it has been shown that M-CSF can induce the expression of its own gene. Although sensitivity to M-CSF can be modulated by regulation of receptor expression and function, M-CSF responsiveness is largely determined at a postreceptor level. To date, little is known about the intracellular pathway of M-CSF signal transduction. We have therefore investigated the changes in protein kinase C (PKC) activity upon exposure of monocytes to M-CSF. We show that M-CSF activates and translocates PKC. Inhibition of PKC by the isoquinoline derivative H7 abolishes induction of M-CSF by M-CSF. Furthermore, activation of PKC was pertussis-toxin-sensitive and was associated with the detection of an NF kappa B protein in nuclear extracts of M-CSF-induced blood monocytes but not in monocytes exposed to medium treatment only. The results suggest that M-CSF induction of M-CSF involves G proteins, PKC and NF kappa B. " ], "offsets": [ [ 0, 1446 ] ] } ]

[ { "id": "PMID-1883525_T1", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-1883525_T2", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 34, 39 ] ], "normalized": [] }, { "id": "PMID-1883525_T3", "type": "Protein", "text": [ "Macrophage-colony-stimulating factor" ], "offsets": [ [ 104, 140 ] ], "normalized": [] }, { "id": "PMID-1883525_T4", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 142, 147 ] ], "normalized": [] }, { "id": "PMID-1883525_T5", "type": "Protein", "text": [ "CSF-1" ], "offsets": [ [ 170, 175 ] ], "normalized": [] }, { "id": "PMID-1883525_T6", "type": "Protein", "text": [ "c-fms" ], "offsets": [ [ 363, 368 ] ], "normalized": [] }, { "id": "PMID-1883525_T7", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 406, 411 ] ], "normalized": [] }, { "id": "PMID-1883525_T8", "type": "Protein", "text": [ "c-fms" ], "offsets": [ [ 416, 421 ] ], "normalized": [] }, { "id": "PMID-1883525_T9", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 485, 490 ] ], "normalized": [] }, { "id": "PMID-1883525_T10", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 564, 569 ] ], "normalized": [] }, { "id": "PMID-1883525_T11", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 637, 642 ] ], "normalized": [] }, { "id": "PMID-1883525_T12", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-1883525_T13", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 839, 844 ] ], "normalized": [] }, { "id": "PMID-1883525_T14", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 974, 979 ] ], "normalized": [] }, { "id": "PMID-1883525_T15", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 994, 999 ] ], "normalized": [] }, { "id": "PMID-1883525_T16", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1107, 1112 ] ], "normalized": [] }, { "id": "PMID-1883525_T17", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1116, 1121 ] ], "normalized": [] }, { "id": "PMID-1883525_T18", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1270, 1275 ] ], "normalized": [] }, { "id": "PMID-1883525_T19", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1380, 1385 ] ], "normalized": [] }, { "id": "PMID-1883525_T20", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1399, 1404 ] ], "normalized": [] } ]

[ { "id": "PMID-1883525_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_E2" }, { "role": "Cause", "ref_id": "PMID-1883525_T2" } ] }, { "id": "PMID-1883525_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 20, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T1" } ] }, { "id": "PMID-1883525_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 265, 272 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T4" } ] }, { "id": "PMID-1883525_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 422, 432 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T7" } ] }, { "id": "PMID-1883525_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 422, 432 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T8" } ] }, { "id": "PMID-1883525_E6", "type": "Positive_regulation", "trigger": { "text": [ "act" ], "offsets": [ [ 495, 498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T9" } ] }, { "id": "PMID-1883525_E7", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 574, 580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_E8" }, { "role": "Cause", "ref_id": "PMID-1883525_T10" } ] }, { "id": "PMID-1883525_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 585, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T10" } ] }, { "id": "PMID-1883525_E9", "type": "Negative_regulation", "trigger": { "text": [ "abolishes" ], "offsets": [ [ 1084, 1093 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_E10" } ] }, { "id": "PMID-1883525_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1094, 1103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T16" }, { "role": "Cause", "ref_id": "PMID-1883525_T17" } ] }, { "id": "PMID-1883525_E11", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1386, 1395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1883525_T20" }, { "role": "Cause", "ref_id": "PMID-1883525_T19" } ] } ]

[ { "id": "PMID-1883525_1", "entity_ids": [ "PMID-1883525_T4", "PMID-1883525_T3" ] } ]

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[ { "id": "PMID-1896644__text", "type": "abstract", "text": [ "HIV1 infection of human monocytes and macrophages promotes induction or translocation of NF-KB-related factors. \nIn 1991, we demonstrated, using electrophoretic mobility shift assays, that 3 different factors (termed B1, B2 and B3) with affinity for the KB-enhancer target sequence were specifically detected in nuclear extracts from HIV1-infected monocytes and macrophages. The B2 factor was induced in the nuclei of these cells only upon HIV1 infection. The B3 factor was only slightly evident in nuclei of uninfected cells but was readily detectable in nuclei of infected monocytes. Its expression remained very low in nuclei of HIV1-infected macrophages. In this paper, we demonstrate that the B2 factor is expressed in the cytosol of monocytes and macrophages as a DNA-binding protein, indicating that it is not associated with an inhibitor (IKB). This factor remained clustered in the cytosol and was translocated to the nuclei only after HIV1 infection. The B3 factor is detected in the cytosol only when cells are HIV1-infected. The role of HIV1 infection in the expression and the translocation of these factors is discussed. " ], "offsets": [ [ 0, 1135 ] ] } ]

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[ { "id": "PMID-1896645__text", "type": "abstract", "text": [ "Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression. \nCells of the monocyte-macrophage lineage are important targets of HIV infection. We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor alpha (TNF alpha) is associated with expression of nuclear factor kappa B (NF-kappa B). In parallel with such differentiation, HIV transcription, monitored using an HIV long terminal repeat reporter gene construct, is activated in such cells under the influence of enhanced NF-kappa B expression. Also, in a promonocyte cell line chronically infected with HIV, NF-kappa B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF alpha. Thus, stimulation of monocyte cell lines by phorbol esters or TNF alpha induces cell differentiation and activates HIV transcription. Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages. " ], "offsets": [ [ 0, 1123 ] ] } ]

[ { "id": "PMID-1896645_T1", "type": "Protein", "text": [ "tumour necrosis factor alpha" ], "offsets": [ [ 295, 323 ] ], "normalized": [] }, { "id": "PMID-1896645_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 325, 334 ] ], "normalized": [] }, { "id": "PMID-1896645_T3", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 774, 783 ] ], "normalized": [] }, { "id": "PMID-1896645_T4", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 847, 856 ] ], "normalized": [] } ]

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[ { "id": "PMID-1896645_1", "entity_ids": [ "PMID-1896645_T1", "PMID-1896645_T2" ] } ]

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

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

[]

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[ { "id": "PMID-1903417__text", "type": "abstract", "text": [ "Transforming growth factor-beta suppresses human B lymphocyte Ig production by inhibiting synthesis and the switch from the membrane form to the secreted form of Ig mRNA. \nTransforming growth factor-beta (TGF-beta) inhibits B cell Ig secretion and reduces B cell membrane Ig expression. The addition of TGF-beta to human B lymphocyte cultures stimulated with Staphylococcus aureus Cowan strain I and IL-2 completely inhibited B cell Ig secretion (greater than 90%) and decreased B cell surface IgM, IgD, kappa L chain, and lambda L chain expression. In contrast, TGF-beta had only minimal effects on two other B cell membrane proteins, HLA-DR and CD20. Internal labeling with [35S]methionine and immunoprecipitation with anti-IgM, anti-kappa, and anti-lambda antibodies revealed a striking reduction in kappa L chain in the presence of TGF-beta. A less pronounced reduction in lambda L chain and microH chain was also noted. Northern blot analysis of RNA purified from B cells treated with TGF-beta for varying time intervals revealed a significant decrease in steady state kappa and lambda L chain mRNA levels. Furthermore, a significant decrease in the switch from the membrane forms of mu and gamma to their respective secreted forms was noted in the presence of TGF-beta. Nuclear run-on experiments demonstrated decreased transcription of kappa L chain. The effects of TGF-beta on two transcriptional regulatory factors, Oct-2 and nuclear factor (NF) kappa B, known to be important in Ig gene transcription were examined. Oct-2 mRNA levels and both Oct-2 and NF-kappa B proteins in nuclear extracts were not altered by treatment with TGF-beta. In contrast, levels of the transcriptional factor AP-1, which is not known to be important in B cell Ig production, were reduced by TGF-beta. These findings demonstrate that TGF-beta decreases B lymphocyte Ig secretion by inhibiting the synthesis of Ig mRNA and inhibiting the switch from the membrane form to the secreted forms of mu and gamma mRNA. The mechanism by which TGF-beta inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of NF-kappa B or Oct-2 to their respective target sequences. " ], "offsets": [ [ 0, 2186 ] ] } ]

[ { "id": "PMID-1903417_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 400, 404 ] ], "normalized": [] }, { "id": "PMID-1903417_T2", "type": "Protein", "text": [ "kappa L chain" ], "offsets": [ [ 504, 517 ] ], "normalized": [] }, { "id": "PMID-1903417_T3", "type": "Protein", "text": [ "lambda L chain" ], "offsets": [ [ 523, 537 ] ], "normalized": [] }, { "id": "PMID-1903417_T4", "type": "Protein", "text": [ "CD20" ], "offsets": [ [ 647, 651 ] ], "normalized": [] }, { "id": "PMID-1903417_T5", "type": "Protein", "text": [ "kappa" ], "offsets": [ [ 736, 741 ] ], "normalized": [] }, { "id": "PMID-1903417_T6", "type": "Protein", "text": [ "lambda" ], "offsets": [ [ 752, 758 ] ], "normalized": [] }, { "id": "PMID-1903417_T7", "type": "Protein", "text": [ "kappa L chain" ], "offsets": [ [ 803, 816 ] ], "normalized": [] }, { "id": "PMID-1903417_T8", "type": "Protein", "text": [ "lambda L chain" ], "offsets": [ [ 877, 891 ] ], "normalized": [] }, { "id": "PMID-1903417_T9", "type": "Protein", "text": [ "kappa" ], "offsets": [ [ 1074, 1079 ] ], "normalized": [] }, { "id": "PMID-1903417_T10", "type": "Protein", "text": [ "lambda L chain" ], "offsets": [ [ 1084, 1098 ] ], "normalized": [] }, { "id": "PMID-1903417_T11", "type": "Protein", "text": [ "kappa L chain" ], "offsets": [ [ 1343, 1356 ] ], "normalized": [] }, { "id": "PMID-1903417_T12", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 1425, 1430 ] ], "normalized": [] }, { "id": "PMID-1903417_T13", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 1526, 1531 ] ], "normalized": [] }, { "id": "PMID-1903417_T14", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 1553, 1558 ] ], "normalized": [] }, { "id": "PMID-1903417_T15", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 2142, 2147 ] ], "normalized": [] } ]

[ { "id": "PMID-1903417_E1", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 469, 478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_E3" } ] }, { "id": "PMID-1903417_E2", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 469, 478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_E4" } ] }, { "id": "PMID-1903417_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 538, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T2" } ] }, { "id": "PMID-1903417_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 538, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T3" } ] }, { "id": "PMID-1903417_E5", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 589, 596 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T4" } ] }, { "id": "PMID-1903417_E6", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 790, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T7" } ] }, { "id": "PMID-1903417_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 864, 873 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T8" } ] }, { "id": "PMID-1903417_E8", "type": "Negative_regulation", "trigger": { "text": [ "levels" ], "offsets": [ [ 1104, 1110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T9" } ] }, { "id": "PMID-1903417_E9", "type": "Negative_regulation", "trigger": { "text": [ "levels" ], "offsets": [ [ 1104, 1110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T10" } ] }, { "id": "PMID-1903417_E10", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1316, 1325 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_E11" } ] }, { "id": "PMID-1903417_E11", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1326, 1339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T11" } ] }, { "id": "PMID-1903417_E12", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 1362, 1369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T12" } ] }, { "id": "PMID-1903417_E13", "type": "Regulation", "trigger": { "text": [ "altered" ], "offsets": [ [ 1612, 1619 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T14" } ] }, { "id": "PMID-1903417_E14", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 2099, 2109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_E15" } ] }, { "id": "PMID-1903417_E15", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 2117, 2124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1903417_T15" } ] } ]

[]

[]

[ { "id": "PMID-1907460__text", "type": "abstract", "text": [ "Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. \nHIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals. " ], "offsets": [ [ 0, 1215 ] ] } ]

[ { "id": "PMID-1907460_T1", "type": "Protein", "text": [ "tumour necrosis factor alpha" ], "offsets": [ [ 253, 281 ] ], "normalized": [] }, { "id": "PMID-1907460_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 283, 292 ] ], "normalized": [] }, { "id": "PMID-1907460_T3", "type": "Protein", "text": [ "chloramphenicol acetyl-transferase" ], "offsets": [ [ 861, 895 ] ], "normalized": [] }, { "id": "PMID-1907460_T4", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 897, 900 ] ], "normalized": [] } ]

[ { "id": "PMID-1907460_E1", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 238, 249 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1907460_T2" } ] }, { "id": "PMID-1907460_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 774, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1907460_E4" } ] }, { "id": "PMID-1907460_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 907, 917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1907460_T4" } ] }, { "id": "PMID-1907460_E4", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 924, 931 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1907460_E3" } ] } ]

[ { "id": "PMID-1907460_1", "entity_ids": [ "PMID-1907460_T2", "PMID-1907460_T1" ] }, { "id": "PMID-1907460_2", "entity_ids": [ "PMID-1907460_T4", "PMID-1907460_T3" ] } ]

[]

[ { "id": "PMID-1911548__text", "type": "abstract", "text": [ "A nuclear factor NF-GM2 that interacts with a regulatory region of the GM-CSF gene essential for its induction in responses to T-cell activation: purification from human T-cell leukemia line Jurkat cells and similarity to NF-kappa B. \nActivation of T cells by antigen, lectin, or a combination of phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) leads to the induction of genes for a set of lymphokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF). We demonstrated in earlier studies that the upstream region of the mouse GM-CSF promoter at positions between -95 and -73 is essential for transcriptional activation in response to PMA/A23187. This region contains two DNA-binding motifs, GM2 and GC-box. The GM2 sequence (GGTAGTTCCC) is recognized by an inducible factor NF-GM2; the other (CCGCCC) by constitutive factors A1, A2, and B. To elucidate the mechanism of GM-CSF gene activation, we have purified the inducible factor NF-GM2 from the nuclear extract of stimulated Jurkat cells on the basis of specific DNA-binding activity. The purified NF-GM2 consists of 50 (p50) and 65 kDa (p65) polypeptides and has a binding activity specific for both the GM-CSF and immunoglobulin kappa (GGAAAGTCCC) enhancers. Electrophoretically purified p50 alone can form a protein-DNA complex, but in the mixture, p50 associates preferentially with p65 to form the NF-GM2 complex. In addition, p65 gave per se, with low affinity, a protein-DNA complex that migrated more slowly than native NF-GM2 complex. Furthermore, an antiserum against KBF1 (identical to 50 kDa NF-kappa B protein) reacted with the p50 of NF-GM2, indicating that the NF-GM2 polypeptide cannot be immunologically differentiated from the 50 kDa subunit of NF-kappa B. The purified NF-GM2 activated in vitro transcription from the kappa B enhancer, while it failed to stimulate transcription from the GM-CSF promoter harboring the GM2 sequence. This suggests that the activation mechanism of the GM-CSF gene through the GM2/GC-box sequence is different from that of genes carrying the kappa B enhancer alone. " ], "offsets": [ [ 0, 2105 ] ] } ]

[ { "id": "PMID-1911548_T1", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 71, 77 ] ], "normalized": [] }, { "id": "PMID-1911548_T2", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 431, 479 ] ], "normalized": [] }, { "id": "PMID-1911548_T3", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 481, 487 ] ], "normalized": [] }, { "id": "PMID-1911548_T4", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 563, 569 ] ], "normalized": [] }, { "id": "PMID-1911548_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 907, 913 ] ], "normalized": [] }, { "id": "PMID-1911548_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1111, 1114 ] ], "normalized": [] }, { "id": "PMID-1911548_T7", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1128, 1131 ] ], "normalized": [] }, { "id": "PMID-1911548_T8", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1195, 1201 ] ], "normalized": [] }, { "id": "PMID-1911548_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1280, 1283 ] ], "normalized": [] }, { "id": "PMID-1911548_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1342, 1345 ] ], "normalized": [] }, { "id": "PMID-1911548_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1377, 1380 ] ], "normalized": [] }, { "id": "PMID-1911548_T12", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1422, 1425 ] ], "normalized": [] }, { "id": "PMID-1911548_T13", "type": "Protein", "text": [ "KBF1" ], "offsets": [ [ 1568, 1572 ] ], "normalized": [] }, { "id": "PMID-1911548_T14", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1631, 1634 ] ], "normalized": [] }, { "id": "PMID-1911548_T15", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1897, 1903 ] ], "normalized": [] }, { "id": "PMID-1911548_T16", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1992, 1998 ] ], "normalized": [] }, { "id": "PMID-1911548_T26", "type": "Entity", "text": [ "enhancers" ], "offsets": [ [ 1240, 1249 ] ], "normalized": [] } ]

[ { "id": "PMID-1911548_E1", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 83, 92 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_E3" } ] }, { "id": "PMID-1911548_E2", "type": "Gene_expression", "trigger": { "text": [ "induction" ], "offsets": [ [ 101, 110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T1" } ] }, { "id": "PMID-1911548_E3", "type": "Regulation", "trigger": { "text": [ "responses" ], "offsets": [ [ 114, 123 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_E2" } ] }, { "id": "PMID-1911548_E4", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 363, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_E5" } ] }, { "id": "PMID-1911548_E5", "type": "Gene_expression", "trigger": { "text": [ "induction" ], "offsets": [ [ 376, 385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T3" } ] }, { "id": "PMID-1911548_E6", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 615, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_E7" } ] }, { "id": "PMID-1911548_E7", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 629, 655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T4" } ] }, { "id": "PMID-1911548_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 919, 929 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T5" } ] }, { "id": "PMID-1911548_E9", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1156, 1172 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T8" }, { "role": "Site", "ref_id": "PMID-1911548_T26" } ] }, { "id": "PMID-1911548_E10", "type": "Binding", "trigger": { "text": [ "complex" ], "offsets": [ [ 1313, 1320 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T9" } ] }, { "id": "PMID-1911548_E11", "type": "Binding", "trigger": { "text": [ "associates" ], "offsets": [ [ 1346, 1356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T10" }, { "role": "Theme", "ref_id": "PMID-1911548_T11" } ] }, { "id": "PMID-1911548_E12", "type": "Binding", "trigger": { "text": [ "complex" ], "offsets": [ [ 1472, 1479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T12" } ] }, { "id": "PMID-1911548_E13", "type": "Binding", "trigger": { "text": [ "reacted" ], "offsets": [ [ 1614, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T14" } ] }, { "id": "PMID-1911548_E14", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 1864, 1873 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_E15" } ] }, { "id": "PMID-1911548_E15", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1874, 1887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T15" } ] }, { "id": "PMID-1911548_E16", "type": "Gene_expression", "trigger": { "text": [ "activation" ], "offsets": [ [ 1964, 1974 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_T16" } ] }, { "id": "PMID-1911548_E17", "type": "Positive_regulation", "trigger": { "text": [ "through" ], "offsets": [ [ 2004, 2011 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1911548_E16" } ] } ]

[ { "id": "PMID-1911548_1", "entity_ids": [ "PMID-1911548_T3", "PMID-1911548_T2" ] } ]

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[ { "id": "PMID-1931834__text", "type": "abstract", "text": [ "Synergism between two distinct elements of the HTLV-I enhancer during activation by the trans-activator of HTLV-I. \nWe have conducted functional studies of the enhancer elements of human T-cell leukemia virus type I (HTLV-I) using the human T-cell lines Jurkat and MOLT 4, which are negative for HTLV-I, and MT-2 and TL-Mor, which carry the proviral genome of HTLV-I. Two distinct elements have been implicated in function of the HTLV-I enhancer. One is the 21-base-pair (bp) core element that is responsible for trans-activation by the HTLV-I trans-activator p40tax and that has the ability to bind to cyclic-AMP responsive element binding factor (CREB)-like factor(s). The other is a region interposed between the 21-bp elements. In this study we demonstrate that a subfragment (C26) in the region between the 21-bp elements is involved in trans-activation by p40tax, possibly through binding to an NF-kappa B-like nuclear factor or factors. Formation of the protein-DNA complex with the C26 subfragment was positively affected by p40tax. The C26 element conferred partial responsiveness to p40tax when linked to one copy of the 21-bp element that, by itself, showed little activation in response to p40tax. However, the C26 element alone, even when repeated, could not be activated by p40tax, unlike other NF-kappa B-binding elements. In contrast, the C26 element itself was profoundly activated upon stimulation with 12-O-tetradecanoylphorbol-13-acetate. These findings therefore suggest that the HTLV-I enhancer contains multiple functional elements, including binding sites for at least CREB- and NF-kappa B-like factors, which synergistically cooperate in activation of the HTLV-I enhancer in response to p40tax. Our results also demonstrate that TPA-dependent activation of the HTLV-I enhancer may be mediated through the C26 element. " ], "offsets": [ [ 0, 1843 ] ] } ]

[ { "id": "PMID-1931834_T1", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 560, 566 ] ], "normalized": [] }, { "id": "PMID-1931834_T2", "type": "Protein", "text": [ "cyclic-AMP responsive element binding factor" ], "offsets": [ [ 603, 647 ] ], "normalized": [] }, { "id": "PMID-1931834_T3", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 649, 653 ] ], "normalized": [] }, { "id": "PMID-1931834_T4", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 862, 868 ] ], "normalized": [] }, { "id": "PMID-1931834_T5", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 1033, 1039 ] ], "normalized": [] }, { "id": "PMID-1931834_T6", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 1093, 1099 ] ], "normalized": [] }, { "id": "PMID-1931834_T7", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 1202, 1208 ] ], "normalized": [] }, { "id": "PMID-1931834_T8", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 1288, 1294 ] ], "normalized": [] }, { "id": "PMID-1931834_T9", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 1593, 1597 ] ], "normalized": [] }, { "id": "PMID-1931834_T10", "type": "Protein", "text": [ "p40tax" ], "offsets": [ [ 1712, 1718 ] ], "normalized": [] } ]

[ { "id": "PMID-1931834_E1", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 595, 599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1931834_T3" } ] } ]

[ { "id": "PMID-1931834_1", "entity_ids": [ "PMID-1931834_T3", "PMID-1931834_T2" ] } ]

[]

[ { "id": "PMID-1939341__text", "type": "abstract", "text": [ "Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of c-fos and c-jun (AP-1). \nPrevious studies have shown that treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of monocytic differentiation and expression of the c-jun and c-fos early response genes. The present work demonstrates that the glucocorticoid dexamethasone inhibits TPA-induced increases in c-jun and c-fos mRNA levels in U-937 leukemia cells. These findings were associated with a block in appearance of the monocytic phenotype, including inhibition of TPA-induced increases in lamin A, lamin C, and vimentin transcripts. Other studies have demonstrated that TPA-induced monocytic differentiation and expression of the c-jun and c-fos genes in myeloid leukemia cells are regulated by protein kinase C (PKC). The finding that dexamethasone has no effect on TPA-induced activation of PKC suggests that this glucocorticoid inhibits signals downstream or parallel to this enzyme. Nuclear run-on assays demonstrate that: (1) induction of c-jun and c-fos expression by TPA is regulated by transcriptional mechanisms, (2) TPA-induced expression of c-jun and c-fos does not require protein synthesis, and (3) TPA-induced expression of both genes is inhibited at the transcriptional level by dexamethasone. To further define the effects of dexamethasone at the molecular level, we prepared a series of deleted c-jun promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene. Increases in CAT activity during transient expression of these constructs in TPA-treated U-937 cells could be assigned to the region (-97 to -20) of the promoter that contains the AP-1 binding site. This induction of CAT activity was sensitive to dexamethasone. These findings suggest that dexamethasone down-regulates TPA-induced transcription of the c-jun gene during monocytic differentiation by inhibiting activation of the AP-1 site. " ], "offsets": [ [ 0, 2020 ] ] } ]

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"PMID-1939341_E6", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 472, 481 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T6" } ] }, { "id": "PMID-1939341_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 634, 644 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E10" } ] }, { "id": "PMID-1939341_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 634, 644 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E12" } ] }, { "id": "PMID-1939341_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 634, 644 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E11" } ] }, { "id": "PMID-1939341_E10", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 660, 669 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T7" } ] }, { "id": "PMID-1939341_E11", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 660, 669 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T9" } ] }, { "id": "PMID-1939341_E12", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 660, 669 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T8" } ] }, { "id": "PMID-1939341_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 796, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T11" } ] }, { "id": "PMID-1939341_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 796, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T10" } ] }, { "id": "PMID-1939341_E15", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E14" } ] }, { "id": "PMID-1939341_E16", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E13" } ] }, { "id": "PMID-1939341_E17", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 941, 947 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E18" } ] }, { "id": "PMID-1939341_E18", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 963, 973 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T12" } ] }, { "id": "PMID-1939341_E19", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1115, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E22" } ] }, { "id": "PMID-1939341_E20", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1115, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E21" } ] }, { "id": "PMID-1939341_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1144, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T14" } ] }, { "id": "PMID-1939341_E22", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1144, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T13" } ] }, { "id": "PMID-1939341_E23", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1165, 1174 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E20" } ] }, { "id": "PMID-1939341_E24", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1165, 1174 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E19" } ] }, { "id": "PMID-1939341_E25", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1214, 1221 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E27" } ] }, { "id": "PMID-1939341_E26", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1214, 1221 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E28" } ] }, { "id": "PMID-1939341_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1222, 1232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T15" } ] }, { "id": "PMID-1939341_E28", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1222, 1232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T16" } ] }, { "id": "PMID-1939341_E29", "type": "Positive_regulation", "trigger": { "text": [ "require" ], "offsets": [ [ 1261, 1268 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E25" } ] }, { "id": "PMID-1939341_E30", "type": "Positive_regulation", "trigger": { "text": [ "require" ], "offsets": [ [ 1261, 1268 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E26" } ] }, { "id": "PMID-1939341_E31", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1300, 1307 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E36" } ] }, { "id": "PMID-1939341_E32", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1300, 1307 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E35" } ] }, { "id": "PMID-1939341_E33", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1336, 1345 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E32" } ] }, { "id": "PMID-1939341_E34", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1336, 1345 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E31" } ] }, { "id": "PMID-1939341_E35", "type": "Transcription", "trigger": { "text": [ "at the transcriptional level" ], "offsets": [ [ 1346, 1374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T14" } ] }, { "id": "PMID-1939341_E36", "type": "Transcription", "trigger": { "text": [ "at the transcriptional level" ], "offsets": [ [ 1346, 1374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T13" } ] }, { "id": "PMID-1939341_E37", "type": "Positive_regulation", "trigger": { "text": [ "Increases" ], "offsets": [ [ 1581, 1590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T20" } ] }, { "id": "PMID-1939341_E38", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1785, 1794 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T21" } ] }, { "id": "PMID-1939341_E39", "type": "Regulation", "trigger": { "text": [ "sensitive" ], "offsets": [ [ 1815, 1824 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E38" } ] }, { "id": "PMID-1939341_E40", "type": "Negative_regulation", "trigger": { "text": [ "down-regulates" ], "offsets": [ [ 1885, 1899 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E42" } ] }, { "id": "PMID-1939341_E41", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1904, 1911 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_E42" } ] }, { "id": "PMID-1939341_E42", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1912, 1925 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1939341_T22" } ] } ]

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[ { "id": "PMID-1944294__text", "type": "abstract", "text": [ "Evaluation of the role of ligand and thermal activation of specific DNA binding by in vitro synthesized human glucocorticoid receptor. \nWe have used a DNA-binding/immunoprecipitation assay to analyze the capacity of human glucocorticoid receptor (hGR), generated in rabbit reticulocyte lysates, to bind DNA. In vitro translated hGR was indistinguishable from native hGR, as determined by migration on sodium dodecyl sulfate-polyacrylamide gels, sedimentation on sucrose density gradients, and reactivity with antipeptide antibodies generated against hGR. In addition, cell-free synthesized hGR was capable of specific binding to glucocorticoid response element (GRE)-containing DNA fragments. Using this assay system, we have evaluated the contributions of ligand binding and heat activation to DNA binding by these glucocorticoid receptors. In vitro translated hGR was capable of selective DNA binding even in the absence of glucocorticoid. Treatment with dexamethasone or the antiglucocorticoid RU486 had no additional effect on the DNA-binding capacity when receptor preparations were maintained at 0 C (no activation). In contrast, addition of either ligand or antagonist in combination with a heat activation step promoted DNA binding by approximately 3-fold over that of heat-activated unliganded receptors. Agonist (dexamethasone) was slightly more effective in supporting specific DNA binding than antagonist (RU486). DNA binding by in vitro synthesized GR was blocked by the addition of sodium molybdate to the receptor preparations before steroid addition and thermal activation. Addition of KCl resulted in less DNA binding either due to blockage of DNA-receptor complex formation or disruption of the complexes. The specificity of DNA binding by cell-free synthesized hGR was analyzed further by examining the abilities of various DNAs to compete for binding to a naturally occurring GRE found in the mouse mammary tumor virus-long terminal repeat. Oligonucleotides containing the consensus GRE were the most efficient competitors, and fragments containing regulatory sequences from glucocorticoid-repressible genes were somewhat competitive, whereas single stranded oligonucleotides were unable to compete for mouse mammary tumor virus-long terminal repeat DNA binding, except when competitor was present at extremely high concentrations. Together these studies indicate that hGR synthesized in rabbit reticulocyte lysates displays many of the same properties, including GRE-specific DNA binding, observed for glucocorticoid receptor present in cytosolic extracts of mammalian cells and tissues. Similarities between the effects of dexamethasone and RU486 suggest that the antiglucocorticoid properties of RU486 do not occur at the level of specific DNA binding. " ], "offsets": [ [ 0, 2776 ] ] } ]

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[ { "id": "PMID-1945879__text", "type": "abstract", "text": [ "One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter. \nThe inducible, T cell-specific enhancers of murine and human Interleukin 2 (Il-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this so-called TCEd (distal T cell element) acts as an inducible proto-enhancer element in E14 T lymphoma cells, but not in HeLa cells. In extracts of induced, Il-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the proto-enhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50 kD and 105 kD; the former seems to be related to the 50 kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the 'converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and HeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the Il-2 gene. " ], "offsets": [ [ 0, 1477 ] ] } ]

[ { "id": "PMID-1945879_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 107, 120 ] ], "normalized": [] }, { "id": "PMID-1945879_T2", "type": "Protein", "text": [ "Interleukin 2" ], "offsets": [ [ 193, 206 ] ], "normalized": [] }, { "id": "PMID-1945879_T3", "type": "Protein", "text": [ "Il-2" ], "offsets": [ [ 208, 212 ] ], "normalized": [] }, { "id": "PMID-1945879_T4", "type": "Protein", "text": [ "Il-2" ], "offsets": [ [ 495, 499 ] ], "normalized": [] }, { "id": "PMID-1945879_T5", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "PMID-1945879_T6", "type": "Protein", "text": [ "T cell factor 1" ], "offsets": [ [ 626, 641 ] ], "normalized": [] }, { "id": "PMID-1945879_T7", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 700, 705 ] ], "normalized": [] }, { "id": "PMID-1945879_T8", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 881, 886 ] ], "normalized": [] }, { "id": "PMID-1945879_T9", "type": "Protein", "text": [ "Il-2" ], "offsets": [ [ 1466, 1470 ] ], "normalized": [] } ]

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[ { "id": "PMID-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 ] ] } ]

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[ { "id": "PMID-1946405__text", "type": "abstract", "text": [ "Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site. \nWe have determined that the developmental control of immunoglobulin kappa 3' enhancer (kappa E3') activity is the result of the combined influence of positive- and negative-acting elements. We show that a central core in the kappa E3' enhancer is active at the pre-B-cell stage but is repressed by flanking negative-acting elements. The negative-acting sequences repress enhancer activity in a position- and orientation-independent manner at the pre-B-cell stage. We have isolated a human cDNA clone encoding a zinc finger protein (NF-E1) that binds to the negative-acting segment of the kappa E3' enhancer. This protein also binds to the immunoglobulin heavy-chain enhancer mu E1 site. NF-E1 is encoded by the same gene as the YY-1 protein, which binds to the adeno-associated virus P5 promoter. NF-E1 is also the human homologue of the mouse delta protein, which binds to ribosomal protein gene promoters. The predicted amino acid sequence of this protein contains features characteristic of transcriptional activators as well as transcriptional repressors. Cotransfection studies with this cDNA indicate that it can repress basal promoter activity. The apparent dual function of this protein is discussed. " ], "offsets": [ [ 0, 1375 ] ] } ]

[ { "id": "PMID-1946405_T1", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 46, 51 ] ], "normalized": [] }, { "id": "PMID-1946405_T2", "type": "Protein", "text": [ "YY-1" ], "offsets": [ [ 53, 57 ] ], "normalized": [] }, { "id": "PMID-1946405_T3", "type": "Protein", "text": [ "delta" ], "offsets": [ [ 59, 64 ] ], "normalized": [] }, { "id": "PMID-1946405_T4", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 698, 703 ] ], "normalized": [] }, { "id": "PMID-1946405_T5", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 853, 858 ] ], "normalized": [] }, { "id": "PMID-1946405_T6", "type": "Protein", "text": [ "YY-1" ], "offsets": [ [ 894, 898 ] ], "normalized": [] }, { "id": "PMID-1946405_T7", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 963, 968 ] ], "normalized": [] }, { "id": "PMID-1946405_T8", "type": "Protein", "text": [ "delta" ], "offsets": [ [ 1010, 1015 ] ], "normalized": [] } ]

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[]