id
stringlengths 7
8
| document_id
stringlengths 7
8
| passages
list | entities
list | events
list | coreferences
list | relations
list |
|---|---|---|---|---|---|---|
7721885 | 7721885 | [
{
"id": "7721885__text",
"type": "abstract",
"text": [
"Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. \nOur previous studies in human monocytes have demonstrated that interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha by blocking gene transcription. Using electrophoretic mobility shift assays (EMSA), we now show that, in monocytes stimulated with LPS or TNF alpha, IL-10 inhibits nuclear stimulation of nuclear factor kappa B (NF kappa B), a transcription factor involved in the expression of inflammatory cytokine genes. Several other transcription factors including NF-IL-6, AP-1, AP-2, GR, CREB, Oct-1, and Sp-1 are not affected by IL-10. This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness. Furthermore, compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS-stimulated monocytes. Taken together, these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes. IL-4, another cytokine that inhibits cytokine mRNA accumulation in monocytes, shows little inhibitory effect on LPS-induced NF kappa B activation. Further examination reveals that, unlike IL-10, IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription. These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms. "
],
"offsets": [
[
0,
1822
]
]
}
] | [
{
"id": "7721885_T1",
"type": "Protein",
"text": [
"Interleukin (IL)-10"
],
"offsets": [
[
0,
19
]
],
"normalized": []
},
{
"id": "7721885_T2",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
96,
101
]
],
"normalized": []
},
{
"id": "7721885_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
106,
110
]
],
"normalized": []
},
{
"id": "7721885_T4",
"type": "Protein",
"text": [
"interleukin (IL)-10"
],
"offsets": [
[
228,
247
]
],
"normalized": []
},
{
"id": "7721885_T5",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
331,
340
]
],
"normalized": []
},
{
"id": "7721885_T6",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
342,
346
]
],
"normalized": []
},
{
"id": "7721885_T7",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
348,
352
]
],
"normalized": []
},
{
"id": "7721885_T8",
"type": "Protein",
"text": [
"tumor necrosis factor (TNF)-alpha"
],
"offsets": [
[
358,
391
]
],
"normalized": []
},
{
"id": "7721885_T9",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
530,
539
]
],
"normalized": []
},
{
"id": "7721885_T10",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
541,
546
]
],
"normalized": []
},
{
"id": "7721885_T11",
"type": "Protein",
"text": [
"NF-IL-6"
],
"offsets": [
[
744,
751
]
],
"normalized": []
},
{
"id": "7721885_T12",
"type": "Protein",
"text": [
"AP-1"
],
"offsets": [
[
753,
757
]
],
"normalized": []
},
{
"id": "7721885_T13",
"type": "Protein",
"text": [
"AP-2"
],
"offsets": [
[
759,
763
]
],
"normalized": []
},
{
"id": "7721885_T14",
"type": "Protein",
"text": [
"GR"
],
"offsets": [
[
765,
767
]
],
"normalized": []
},
{
"id": "7721885_T15",
"type": "Protein",
"text": [
"CREB"
],
"offsets": [
[
769,
773
]
],
"normalized": []
},
{
"id": "7721885_T16",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
775,
780
]
],
"normalized": []
},
{
"id": "7721885_T17",
"type": "Protein",
"text": [
"Sp-1"
],
"offsets": [
[
786,
790
]
],
"normalized": []
},
{
"id": "7721885_T18",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
811,
816
]
],
"normalized": []
},
{
"id": "7721885_T19",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
847,
852
]
],
"normalized": []
},
{
"id": "7721885_T20",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
949,
954
]
],
"normalized": []
},
{
"id": "7721885_T21",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
1383,
1388
]
],
"normalized": []
},
{
"id": "7721885_T22",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1452,
1456
]
],
"normalized": []
},
{
"id": "7721885_T23",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
1640,
1645
]
],
"normalized": []
},
{
"id": "7721885_T24",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1647,
1651
]
],
"normalized": []
},
{
"id": "7721885_T25",
"type": "Protein",
"text": [
"IL-10"
],
"offsets": [
[
1754,
1759
]
],
"normalized": []
},
{
"id": "7721885_T26",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1764,
1768
]
],
"normalized": []
}
] | [
{
"id": "7721885_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
248,
256
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E5"
}
]
},
{
"id": "7721885_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
248,
256
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E8"
}
]
},
{
"id": "7721885_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
248,
256
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E6"
}
]
},
{
"id": "7721885_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
248,
256
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E7"
}
]
},
{
"id": "7721885_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
282,
292
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E12"
}
]
},
{
"id": "7721885_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
282,
292
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E9"
}
]
},
{
"id": "7721885_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
282,
292
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E10"
}
]
},
{
"id": "7721885_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
282,
292
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_E11"
}
]
},
{
"id": "7721885_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
293,
303
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T6"
}
]
},
{
"id": "7721885_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
293,
303
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T7"
}
]
},
{
"id": "7721885_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
293,
303
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T5"
}
]
},
{
"id": "7721885_E12",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
293,
303
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T8"
}
]
},
{
"id": "7721885_E13",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T13"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
},
{
"id": "7721885_E14",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T12"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
},
{
"id": "7721885_E15",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T15"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
},
{
"id": "7721885_E16",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T16"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
},
{
"id": "7721885_E17",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T14"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
},
{
"id": "7721885_E18",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T11"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
},
{
"id": "7721885_E19",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
799,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7721885_T17"
},
{
"role": "Cause",
"ref_id": "7721885_T18"
}
]
}
] | [] | [] |
8659190 | 8659190 | [
{
"id": "8659190__text",
"type": "abstract",
"text": [
"Transcription factors of T and B lymphocytes--basic research and clinical perspectives for gastroenterology. \nTissue specific regulation of gene expression by transcription factors is a fascinating new field in molecular immunology. This review summarizes data on specific regulation of promoters and enhancers by nuclear trans-acting factors in lymphocytes. The structural classes of transcription factors are described and basic methods for detection and analysis of transcription factors are detailed. Furthermore, the most important trans-acting factors of T and B lymphocytes (e.g. NF-kB, NF-AT and STAT families) and their functional importance are described. Several methods for specific down-regulation of transcription factors are shown that may be relevant to treatment of human disease. The data are discussed with regard to their potential clinical relevance for gastroenterology. "
],
"offsets": [
[
0,
893
]
]
}
] | [] | [] | [] | [] |
7862168 | 7862168 | [
{
"id": "7862168__text",
"type": "abstract",
"text": [
"Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. \nThe interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins. "
],
"offsets": [
[
0,
1545
]
]
}
] | [
{
"id": "7862168_T1",
"type": "Protein",
"text": [
"interleukin-2 receptor alpha-chain"
],
"offsets": [
[
33,
67
]
],
"normalized": []
},
{
"id": "7862168_T2",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
133,
138
]
],
"normalized": []
},
{
"id": "7862168_T3",
"type": "Protein",
"text": [
"HMG-I(Y)"
],
"offsets": [
[
140,
148
]
],
"normalized": []
},
{
"id": "7862168_T4",
"type": "Protein",
"text": [
"interleukin 2 receptor alpha-chain"
],
"offsets": [
[
187,
221
]
],
"normalized": []
},
{
"id": "7862168_T5",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
223,
234
]
],
"normalized": []
},
{
"id": "7862168_T6",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
580,
585
]
],
"normalized": []
},
{
"id": "7862168_T7",
"type": "Protein",
"text": [
"HMG-I(Y)"
],
"offsets": [
[
590,
598
]
],
"normalized": []
},
{
"id": "7862168_T8",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
694,
699
]
],
"normalized": []
},
{
"id": "7862168_T9",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
735,
746
]
],
"normalized": []
},
{
"id": "7862168_T10",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
786,
791
]
],
"normalized": []
},
{
"id": "7862168_T11",
"type": "Protein",
"text": [
"HMG-I(Y)"
],
"offsets": [
[
799,
807
]
],
"normalized": []
},
{
"id": "7862168_T12",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
931,
936
]
],
"normalized": []
},
{
"id": "7862168_T13",
"type": "Protein",
"text": [
"HMG-I"
],
"offsets": [
[
964,
969
]
],
"normalized": []
},
{
"id": "7862168_T14",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
990,
993
]
],
"normalized": []
},
{
"id": "7862168_T15",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
998,
1003
]
],
"normalized": []
},
{
"id": "7862168_T16",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1423,
1434
]
],
"normalized": []
},
{
"id": "7862168_T17",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
1507,
1512
]
],
"normalized": []
},
{
"id": "7862168_T27",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
747,
755
]
],
"normalized": []
}
] | [
{
"id": "7862168_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_E2"
}
]
},
{
"id": "7862168_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
73,
83
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T1"
}
]
},
{
"id": "7862168_E3",
"type": "Binding",
"trigger": {
"text": [
"interactions"
],
"offsets": [
[
112,
124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T2"
}
]
},
{
"id": "7862168_E4",
"type": "Binding",
"trigger": {
"text": [
"interactions"
],
"offsets": [
[
112,
124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T3"
}
]
},
{
"id": "7862168_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
265,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T5"
}
]
},
{
"id": "7862168_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
287,
295
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_E5"
}
]
},
{
"id": "7862168_E7",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
574,
579
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T7"
}
]
},
{
"id": "7862168_E8",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
574,
579
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T6"
}
]
},
{
"id": "7862168_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
700,
710
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T8"
}
]
},
{
"id": "7862168_E10",
"type": "Transcription",
"trigger": {
"text": [
"Transcription"
],
"offsets": [
[
712,
725
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T9"
}
]
},
{
"id": "7862168_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"from"
],
"offsets": [
[
726,
730
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_E10"
},
{
"role": "Cause",
"ref_id": "7862168_T9"
},
{
"role": "CSite",
"ref_id": "7862168_T27"
}
]
},
{
"id": "7862168_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
760,
769
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_E11"
}
]
},
{
"id": "7862168_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"Coexpression"
],
"offsets": [
[
834,
846
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T10"
}
]
},
{
"id": "7862168_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"Coexpression"
],
"offsets": [
[
834,
846
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T11"
}
]
},
{
"id": "7862168_E15",
"type": "Binding",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
948,
958
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T12"
},
{
"role": "Theme",
"ref_id": "7862168_T15"
}
]
},
{
"id": "7862168_E16",
"type": "Binding",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
948,
958
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T12"
},
{
"role": "Theme",
"ref_id": "7862168_T14"
}
]
},
{
"id": "7862168_E17",
"type": "Binding",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
948,
958
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T12"
},
{
"role": "Theme",
"ref_id": "7862168_T13"
}
]
},
{
"id": "7862168_E18",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
1381,
1389
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_E19"
}
]
},
{
"id": "7862168_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1440,
1450
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7862168_T16"
}
]
}
] | [
{
"id": "7862168_1",
"entity_ids": [
"7862168_T4",
"7862168_T5"
]
}
] | [] |
9394832 | 9394832 | [
{
"id": "9394832__text",
"type": "abstract",
"text": [
"Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B. \nThe interleukin-1 receptor type I (IL-1RI) is associated with other proteins thus forming a complex system by which IL-1 exerts its various signals. The initiating event is still uncertain, but activation of a recently described receptor-associated protein kinase is one of the earliest events detectable (Martin et al., Eur.J.Immunol.1994.24: 1566). IL-1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation. We therefore investigated whether the activation of the IL-1RI-associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL-1-mediated NF-kappa B activation. A murine T cell line, EL4, was stimulated with IL-1 with and without pretreatment with different compounds known to influence the cellular redox status. Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL-1-induced activation of the IL-1RI-associated protein kinase. N-Acetylcysteine, alpha,alpha'-dipyridyl, aminotriazole or nitrofurantoin did not show any effect. The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine. The described conditions which inhibited or prevented the activation of the IL-1RI-associated kinase similarly impaired the activation of NF-kappa B in EL4 cells. From these observations we conclude that free thiols in the IL-1RI complex are essential for the activation of the IL-1RI-associated protein kinase and that this process is mandatory for IL-1 signaling leading to NF-kappa B activation. "
],
"offsets": [
[
0,
1788
]
]
}
] | [
{
"id": "9394832_T1",
"type": "Protein",
"text": [
"IL-1 receptor"
],
"offsets": [
[
75,
88
]
],
"normalized": []
},
{
"id": "9394832_T2",
"type": "Protein",
"text": [
"interleukin-1 receptor type I"
],
"offsets": [
[
136,
165
]
],
"normalized": []
},
{
"id": "9394832_T3",
"type": "Protein",
"text": [
"IL-1RI"
],
"offsets": [
[
167,
173
]
],
"normalized": []
},
{
"id": "9394832_T4",
"type": "Protein",
"text": [
"IL-1RI"
],
"offsets": [
[
651,
657
]
],
"normalized": []
},
{
"id": "9394832_T5",
"type": "Protein",
"text": [
"IL-1RI"
],
"offsets": [
[
1150,
1156
]
],
"normalized": []
},
{
"id": "9394832_T6",
"type": "Protein",
"text": [
"IL-1RI"
],
"offsets": [
[
1465,
1471
]
],
"normalized": []
},
{
"id": "9394832_T7",
"type": "Protein",
"text": [
"IL-1RI"
],
"offsets": [
[
1612,
1618
]
],
"normalized": []
},
{
"id": "9394832_T8",
"type": "Protein",
"text": [
"IL-1RI"
],
"offsets": [
[
1667,
1673
]
],
"normalized": []
}
] | [
{
"id": "9394832_E1",
"type": "Binding",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
178,
188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9394832_T3"
}
]
}
] | [
{
"id": "9394832_1",
"entity_ids": [
"9394832_T2",
"9394832_T3"
]
}
] | [] |
1896644 | 1896644 | [
{
"id": "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
]
]
}
] | [] | [] | [] | [] |
8757326 | 8757326 | [
{
"id": "8757326__text",
"type": "abstract",
"text": [
"Defective transcription of the IL-2 gene is associated with impaired expression of c-Fos, FosB, and JunB in anergic T helper 1 cells. \nAnergic CD4+ Th cells do not produce IL-2 when challenged with Ag-pulsed accessory cells because of a transcriptional defect. In this work, we report that these anergic T cells are defective in their ability to up-regulate protein binding and transactivation at two critical IL-2 DNA enhancer elements: NF-AT (nuclear factor of activated T cells; a sequence that binds a heterotrimeric NFATp, Fos, and Jun protein complex) and Activator Protein-1 (AP-1) (that binds Fos and Jun heterodimers). Western blot analysis of nuclear extracts showed that the impaired DNA-protein interactions in anergic T cells were associated with poor expression of the inducible AP-1 family members c-Fos, FosB, and JunB. However, the reduced expression of these proteins was not the result of a global TCR/CD3-signaling defect because CD3 cross-linking induced an equivalent increase in intracellular-free calcium ions, as well as NFATp dephosphorylation, translocation to the nucleus, and DNA binding in both normal and anergic T cells. Thus, defective IL-2 gene transcription appears to be due, at least in part, to a selective block in the expression of the AP-1 Fos and Jun family members in anergic T cells. "
],
"offsets": [
[
0,
1328
]
]
}
] | [
{
"id": "8757326_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
31,
35
]
],
"normalized": []
},
{
"id": "8757326_T2",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
83,
88
]
],
"normalized": []
},
{
"id": "8757326_T3",
"type": "Protein",
"text": [
"FosB"
],
"offsets": [
[
90,
94
]
],
"normalized": []
},
{
"id": "8757326_T4",
"type": "Protein",
"text": [
"JunB"
],
"offsets": [
[
100,
104
]
],
"normalized": []
},
{
"id": "8757326_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
172,
176
]
],
"normalized": []
},
{
"id": "8757326_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
410,
414
]
],
"normalized": []
},
{
"id": "8757326_T7",
"type": "Protein",
"text": [
"NFATp"
],
"offsets": [
[
521,
526
]
],
"normalized": []
},
{
"id": "8757326_T8",
"type": "Protein",
"text": [
"Fos"
],
"offsets": [
[
528,
531
]
],
"normalized": []
},
{
"id": "8757326_T9",
"type": "Protein",
"text": [
"Jun"
],
"offsets": [
[
537,
540
]
],
"normalized": []
},
{
"id": "8757326_T10",
"type": "Protein",
"text": [
"Fos"
],
"offsets": [
[
601,
604
]
],
"normalized": []
},
{
"id": "8757326_T11",
"type": "Protein",
"text": [
"Jun"
],
"offsets": [
[
609,
612
]
],
"normalized": []
},
{
"id": "8757326_T12",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
813,
818
]
],
"normalized": []
},
{
"id": "8757326_T13",
"type": "Protein",
"text": [
"FosB"
],
"offsets": [
[
820,
824
]
],
"normalized": []
},
{
"id": "8757326_T14",
"type": "Protein",
"text": [
"JunB"
],
"offsets": [
[
830,
834
]
],
"normalized": []
},
{
"id": "8757326_T15",
"type": "Protein",
"text": [
"NFATp"
],
"offsets": [
[
1046,
1051
]
],
"normalized": []
},
{
"id": "8757326_T16",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1169,
1173
]
],
"normalized": []
},
{
"id": "8757326_T17",
"type": "Protein",
"text": [
"Fos"
],
"offsets": [
[
1281,
1284
]
],
"normalized": []
},
{
"id": "8757326_T18",
"type": "Protein",
"text": [
"Jun"
],
"offsets": [
[
1289,
1292
]
],
"normalized": []
},
{
"id": "8757326_T34",
"type": "Entity",
"text": [
"nucleus"
],
"offsets": [
[
1092,
1099
]
],
"normalized": []
}
] | [
{
"id": "8757326_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"Defective"
],
"offsets": [
[
0,
9
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E2"
}
]
},
{
"id": "8757326_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
10,
23
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T1"
}
]
},
{
"id": "8757326_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"impaired"
],
"offsets": [
[
60,
68
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E8"
}
]
},
{
"id": "8757326_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"impaired"
],
"offsets": [
[
60,
68
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E7"
}
]
},
{
"id": "8757326_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"impaired"
],
"offsets": [
[
60,
68
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E6"
}
]
},
{
"id": "8757326_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
69,
79
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T2"
}
]
},
{
"id": "8757326_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
69,
79
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T3"
}
]
},
{
"id": "8757326_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
69,
79
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T4"
}
]
},
{
"id": "8757326_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"produce"
],
"offsets": [
[
164,
171
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T5"
}
]
},
{
"id": "8757326_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"when"
],
"offsets": [
[
177,
181
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E9"
}
]
},
{
"id": "8757326_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"because of"
],
"offsets": [
[
224,
234
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E10"
}
]
},
{
"id": "8757326_E12",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
498,
503
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T9"
}
]
},
{
"id": "8757326_E13",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
498,
503
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T8"
}
]
},
{
"id": "8757326_E14",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
498,
503
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T7"
}
]
},
{
"id": "8757326_E15",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
595,
600
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T11"
}
]
},
{
"id": "8757326_E16",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
595,
600
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T10"
}
]
},
{
"id": "8757326_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"poor"
],
"offsets": [
[
760,
764
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E21"
}
]
},
{
"id": "8757326_E18",
"type": "Negative_regulation",
"trigger": {
"text": [
"poor"
],
"offsets": [
[
760,
764
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E20"
}
]
},
{
"id": "8757326_E19",
"type": "Negative_regulation",
"trigger": {
"text": [
"poor"
],
"offsets": [
[
760,
764
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E22"
}
]
},
{
"id": "8757326_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
765,
775
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T12"
}
]
},
{
"id": "8757326_E21",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
765,
775
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T13"
}
]
},
{
"id": "8757326_E22",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
765,
775
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T14"
}
]
},
{
"id": "8757326_E23",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
849,
856
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E26"
}
]
},
{
"id": "8757326_E24",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
849,
856
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E25"
}
]
},
{
"id": "8757326_E25",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
857,
867
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T13"
}
]
},
{
"id": "8757326_E26",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
857,
867
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T12"
}
]
},
{
"id": "8757326_E27",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
857,
867
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T14"
}
]
},
{
"id": "8757326_E28",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
968,
975
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E31"
}
]
},
{
"id": "8757326_E29",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
968,
975
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E32"
}
]
},
{
"id": "8757326_E30",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
968,
975
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E32"
},
{
"role": "Cause",
"ref_id": "8757326_E28"
}
]
},
{
"id": "8757326_E31",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1071,
1084
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T15"
},
{
"role": "ToLoc",
"ref_id": "8757326_T34"
}
]
},
{
"id": "8757326_E32",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1109,
1116
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T15"
}
]
},
{
"id": "8757326_E33",
"type": "Negative_regulation",
"trigger": {
"text": [
"defective"
],
"offsets": [
[
1159,
1168
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E34"
}
]
},
{
"id": "8757326_E34",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1179,
1192
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T16"
}
]
},
{
"id": "8757326_E35",
"type": "Positive_regulation",
"trigger": {
"text": [
"due"
],
"offsets": [
[
1207,
1210
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E33"
},
{
"role": "Cause",
"ref_id": "8757326_E37"
}
]
},
{
"id": "8757326_E36",
"type": "Positive_regulation",
"trigger": {
"text": [
"due"
],
"offsets": [
[
1207,
1210
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E33"
},
{
"role": "Cause",
"ref_id": "8757326_E38"
}
]
},
{
"id": "8757326_E37",
"type": "Negative_regulation",
"trigger": {
"text": [
"block"
],
"offsets": [
[
1245,
1250
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E40"
}
]
},
{
"id": "8757326_E38",
"type": "Negative_regulation",
"trigger": {
"text": [
"block"
],
"offsets": [
[
1245,
1250
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_E39"
}
]
},
{
"id": "8757326_E39",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1258,
1268
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T18"
}
]
},
{
"id": "8757326_E40",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1258,
1268
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8757326_T17"
}
]
}
] | [] | [] |
9094628 | 9094628 | [
{
"id": "9094628__text",
"type": "abstract",
"text": [
"Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells. \nThe transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors. Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2), suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution. Despite these findings, the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown. In the studies described in this report, we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells. This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins. In addition, the Ets-NF-kappaB/NFAT interaction requires the presence of DNA binding sites for both proteins, as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins. A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB (p50 + p65) and Ets-1, suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers. Taken together, these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses. These interactions represent a potential target for the development of novel immunosuppressive and antiviral therapies. "
],
"offsets": [
[
0,
2244
]
]
}
] | [
{
"id": "9094628_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1596,
1599
]
],
"normalized": []
},
{
"id": "9094628_T2",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1738,
1741
]
],
"normalized": []
},
{
"id": "9094628_T3",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1744,
1747
]
],
"normalized": []
},
{
"id": "9094628_T4",
"type": "Protein",
"text": [
"Ets-1"
],
"offsets": [
[
1753,
1758
]
],
"normalized": []
}
] | [
{
"id": "9094628_E1",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
1605,
1610
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9094628_T1"
}
]
},
{
"id": "9094628_E2",
"type": "Binding",
"trigger": {
"text": [
"fails to interact"
],
"offsets": [
[
1619,
1636
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9094628_T1"
}
]
}
] | [] | [] |
7718519 | 7718519 | [
{
"id": "7718519__text",
"type": "abstract",
"text": [
"IL-1 receptor and TCR signals synergize to activate NF-kappa B-mediated gene transcription. \nPrevious studies have demonstrated that IL-1 receptor (IL-1R)- and TCR-initiated signals can interact synergistically to increase the rate of transcription of several lymphokine and lymphokine receptor genes during the competence phase of the activation program in T helper lymphocytes. In this report we describe how signals initiated through the type I IL-1R interact with signals from the antigen receptor to synergistically augment the transactivating properties of NF-kappa B. The synergistic antigen receptor initiated signals are mediated through protein kinase C because they can be mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, but not with calcium ionophores; and are staurosporine sensitive but cyclosporine resistant. Gel shift analyses demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1 rather than by antigen receptor signals. Western blot and phosphorylation analyses demonstrate that the synergistic effect on NF-kappa B functional activity is independent of I kappa B alpha (MAD3)-NF-kappa B dissociation in the cytosol and is not associated with I kappa B nuclear translocation. The IL-1-induced NF-kappa B DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis. These results suggest that IL-1 induces both NF-kappa B nuclear translocation and the synthesis of a protein(s) responsible for terminating NF-kappa B-DNA interaction in the nucleus. Antigen receptor signals prolong NF-kappa B-DNA interaction, probably by functionally antagonizing the IL-1-induced synthesis of a protein(s) responsible for the transient NF-kappa B-DNA interaction and consequently synergistically enhance IL-1-induced NF-kappa B-dependent gene transcription. "
],
"offsets": [
[
0,
1891
]
]
}
] | [
{
"id": "7718519_T1",
"type": "Protein",
"text": [
"type I IL-1R"
],
"offsets": [
[
441,
453
]
],
"normalized": []
},
{
"id": "7718519_T2",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1122,
1137
]
],
"normalized": []
},
{
"id": "7718519_T3",
"type": "Protein",
"text": [
"MAD3"
],
"offsets": [
[
1139,
1143
]
],
"normalized": []
}
] | [] | [
{
"id": "7718519_1",
"entity_ids": [
"7718519_T2",
"7718519_T3"
]
}
] | [] |
8871617 | 8871617 | [
{
"id": "8871617__text",
"type": "abstract",
"text": [
"IL-12-induced activation of NK and T cells occurs in the absence of immediate-early activation gene expression. \nThe responses of lymphocytes to IL-2 and IL-12, involving proliferation, differentiation, and cytokine production, are only partially overlapping, and may depend on induced differential expression of specific sets of genes. Using reverse-transcription PCR differential display, we isolated an mRNA species expressed in IL-2- but not IL-12-stimulated NK cells. This was identified as the mRNA encoding the transcription factor egr-1, which is expressed with fast kinetics in T and NK cells upon IL-2, but not IL-12, stimulation. Analysis of the accumulation of mRNA-encoding members of the AP-1 transcription factor family demonstrated that c-fos and junB are also expressed upon stimulation of NK and T cells with IL-2, but not IL-12, whereas expression of c-jun and junD is not modified by either cytokine. Accordingly, increased AP-1 DNA-binding activity and AP-1-dependent transcriptional activity were detected exclusively in IL-2-stimulated cells. Analysis of the expression of genes reported to regulate cytokine-induced proliferation demonstrated that both IL-2 and IL-12 induce c-myc mRNA accumulation in NK and T cells, whereas only IL-2 induces bcl-2 expression. Our data provide the first demonstration that IL-12-mediated activation of T and NK cells does not involve expression of members of the immediate-early activation genes family (egr-1, c-fos, and junB), AP-1 transcriptional activity, or bcl-2 expression. This indicates that functional differences observed in IL-2- and IL-12-stimulated cells may depend, at least in part, on differential gene regulation. "
],
"offsets": [
[
0,
1691
]
]
}
] | [
{
"id": "8871617_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
432,
436
]
],
"normalized": []
},
{
"id": "8871617_T2",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
539,
544
]
],
"normalized": []
},
{
"id": "8871617_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
607,
611
]
],
"normalized": []
},
{
"id": "8871617_T4",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
753,
758
]
],
"normalized": []
},
{
"id": "8871617_T5",
"type": "Protein",
"text": [
"junB"
],
"offsets": [
[
763,
767
]
],
"normalized": []
},
{
"id": "8871617_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
827,
831
]
],
"normalized": []
},
{
"id": "8871617_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
870,
875
]
],
"normalized": []
},
{
"id": "8871617_T8",
"type": "Protein",
"text": [
"junD"
],
"offsets": [
[
880,
884
]
],
"normalized": []
},
{
"id": "8871617_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1043,
1047
]
],
"normalized": []
},
{
"id": "8871617_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1177,
1181
]
],
"normalized": []
},
{
"id": "8871617_T11",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
1199,
1204
]
],
"normalized": []
},
{
"id": "8871617_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1255,
1259
]
],
"normalized": []
},
{
"id": "8871617_T13",
"type": "Protein",
"text": [
"bcl-2"
],
"offsets": [
[
1268,
1273
]
],
"normalized": []
},
{
"id": "8871617_T14",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
1463,
1468
]
],
"normalized": []
},
{
"id": "8871617_T15",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1470,
1475
]
],
"normalized": []
},
{
"id": "8871617_T16",
"type": "Protein",
"text": [
"junB"
],
"offsets": [
[
1481,
1485
]
],
"normalized": []
},
{
"id": "8871617_T17",
"type": "Protein",
"text": [
"bcl-2"
],
"offsets": [
[
1522,
1527
]
],
"normalized": []
},
{
"id": "8871617_T18",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1595,
1599
]
],
"normalized": []
}
] | [
{
"id": "8871617_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
555,
564
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T2"
}
]
},
{
"id": "8871617_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
777,
786
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T4"
}
]
},
{
"id": "8871617_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
777,
786
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T5"
}
]
},
{
"id": "8871617_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"upon"
],
"offsets": [
[
787,
791
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E2"
}
]
},
{
"id": "8871617_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"upon"
],
"offsets": [
[
787,
791
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E3"
}
]
},
{
"id": "8871617_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
856,
866
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T8"
}
]
},
{
"id": "8871617_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
856,
866
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T7"
}
]
},
{
"id": "8871617_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
892,
900
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E7"
}
]
},
{
"id": "8871617_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
892,
900
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E6"
},
{
"role": "Cause",
"ref_id": "8871617_T6"
}
]
},
{
"id": "8871617_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
892,
900
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E7"
},
{
"role": "Cause",
"ref_id": "8871617_T6"
}
]
},
{
"id": "8871617_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
892,
900
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E6"
}
]
},
{
"id": "8871617_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
1192,
1198
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E14"
},
{
"role": "Cause",
"ref_id": "8871617_T10"
}
]
},
{
"id": "8871617_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
1192,
1198
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E14"
}
]
},
{
"id": "8871617_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"accumulation"
],
"offsets": [
[
1210,
1222
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T11"
}
]
},
{
"id": "8871617_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1260,
1267
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_E16"
},
{
"role": "Cause",
"ref_id": "8871617_T12"
}
]
},
{
"id": "8871617_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1274,
1284
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T13"
}
]
},
{
"id": "8871617_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1393,
1403
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T16"
}
]
},
{
"id": "8871617_E18",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1393,
1403
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T14"
}
]
},
{
"id": "8871617_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1393,
1403
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T15"
}
]
},
{
"id": "8871617_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1528,
1538
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8871617_T17"
}
]
}
] | [] | [] |
9188651 | 9188651 | [
{
"id": "9188651__text",
"type": "abstract",
"text": [
"Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF-kappaB-binding sites of the interleukin-8 gene. \nCytomegalovirus (CMV) infection induced interleukin-8 (IL-8) gene transcription in a human monocytic cell line, THP-1 cells, leading to IL-8 secretion. The functional analysis of the IL-8 gene revealed that both AP-1- and NF-kappaB factor-binding elements were involved in conferring the responsiveness to CMV. Moreover, electrophoretic mobility shift assays demonstrated that CMV induced the formation of NF-kappaB and AP-1 complexes. These results suggest that CMV activates these transcriptional factors, resulting in IL-8 gene expression. "
],
"offsets": [
[
0,
730
]
]
}
] | [
{
"id": "9188651_T1",
"type": "Protein",
"text": [
"interleukin-8"
],
"offsets": [
[
30,
43
]
],
"normalized": []
},
{
"id": "9188651_T2",
"type": "Protein",
"text": [
"interleukin-8"
],
"offsets": [
[
166,
179
]
],
"normalized": []
},
{
"id": "9188651_T3",
"type": "Protein",
"text": [
"interleukin-8"
],
"offsets": [
[
227,
240
]
],
"normalized": []
},
{
"id": "9188651_T4",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
242,
246
]
],
"normalized": []
},
{
"id": "9188651_T5",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
323,
327
]
],
"normalized": []
},
{
"id": "9188651_T6",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
370,
374
]
],
"normalized": []
},
{
"id": "9188651_T7",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
708,
712
]
],
"normalized": []
}
] | [
{
"id": "9188651_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
22,
29
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_E2"
}
]
},
{
"id": "9188651_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
44,
54
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_T1"
}
]
},
{
"id": "9188651_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
219,
226
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_E4"
}
]
},
{
"id": "9188651_E4",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
253,
266
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_T4"
}
]
},
{
"id": "9188651_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"leading"
],
"offsets": [
[
312,
319
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_E6"
},
{
"role": "Cause",
"ref_id": "9188651_E3"
}
]
},
{
"id": "9188651_E6",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
328,
337
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_T5"
}
]
},
{
"id": "9188651_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"resulting"
],
"offsets": [
[
695,
704
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_E8"
}
]
},
{
"id": "9188651_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
718,
728
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188651_T7"
}
]
}
] | [
{
"id": "9188651_1",
"entity_ids": [
"9188651_T3",
"9188651_T4"
]
}
] | [] |
8670269 | 8670269 | [
{
"id": "8670269__text",
"type": "abstract",
"text": [
"An alternatively spliced isoform of the Spi-B transcription factor. \nSpi-B is an Ets transcription factor related to the oncoprotein Spi-1/PU.1 and highly expressed in B lymphoid cells. The Ets proteins share a conserved Ets domain that mediates specific DNA binding. Spi-B binds DNA sequences containing a core 5'-GGAA-3' and activates transcription through this motif. Up to date, the biological function of Spi-B remains unknown. Here, we describe the characterization of an alternatively spliced variant of Spi-B, named deltaSpi-B, which has lost the Ets domain. In B lymphoid cells, deltaspi-B and spi-B mRNAs were present simultaneously in a ratio of around 10%. DeltaSpi-B product was not able to bind DNA and was recovered in cytoplasmic cellular extracts. We raise the hypothesis that delta Spi-B might affect Spi-B function by recruiting factors involved in Spi-B activity. "
],
"offsets": [
[
0,
884
]
]
}
] | [
{
"id": "8670269_T1",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
40,
45
]
],
"normalized": []
},
{
"id": "8670269_T2",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
69,
74
]
],
"normalized": []
},
{
"id": "8670269_T3",
"type": "Protein",
"text": [
"Spi-1"
],
"offsets": [
[
133,
138
]
],
"normalized": []
},
{
"id": "8670269_T4",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
139,
143
]
],
"normalized": []
},
{
"id": "8670269_T5",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
268,
273
]
],
"normalized": []
},
{
"id": "8670269_T6",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
410,
415
]
],
"normalized": []
},
{
"id": "8670269_T7",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
511,
516
]
],
"normalized": []
},
{
"id": "8670269_T8",
"type": "Protein",
"text": [
"deltaSpi-B"
],
"offsets": [
[
524,
534
]
],
"normalized": []
},
{
"id": "8670269_T9",
"type": "Protein",
"text": [
"deltaspi-B"
],
"offsets": [
[
588,
598
]
],
"normalized": []
},
{
"id": "8670269_T10",
"type": "Protein",
"text": [
"spi-B"
],
"offsets": [
[
603,
608
]
],
"normalized": []
},
{
"id": "8670269_T11",
"type": "Protein",
"text": [
"DeltaSpi-B"
],
"offsets": [
[
669,
679
]
],
"normalized": []
},
{
"id": "8670269_T12",
"type": "Protein",
"text": [
"delta Spi-B"
],
"offsets": [
[
794,
805
]
],
"normalized": []
},
{
"id": "8670269_T13",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
819,
824
]
],
"normalized": []
},
{
"id": "8670269_T14",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
868,
873
]
],
"normalized": []
},
{
"id": "8670269_T20",
"type": "Entity",
"text": [
"cytoplasmic cellular extracts"
],
"offsets": [
[
734,
763
]
],
"normalized": []
}
] | [
{
"id": "8670269_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
155,
164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T2"
}
]
},
{
"id": "8670269_E2",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
274,
279
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T5"
}
]
},
{
"id": "8670269_E3",
"type": "Transcription",
"trigger": {
"text": [
"present"
],
"offsets": [
[
620,
627
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T10"
}
]
},
{
"id": "8670269_E4",
"type": "Transcription",
"trigger": {
"text": [
"present"
],
"offsets": [
[
620,
627
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T9"
}
]
},
{
"id": "8670269_E5",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
704,
708
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T11"
}
]
},
{
"id": "8670269_E6",
"type": "Localization",
"trigger": {
"text": [
"recovered"
],
"offsets": [
[
721,
730
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T11"
},
{
"role": "AtLoc",
"ref_id": "8670269_T20"
}
]
},
{
"id": "8670269_E7",
"type": "Regulation",
"trigger": {
"text": [
"affect"
],
"offsets": [
[
812,
818
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8670269_T13"
}
]
}
] | [
{
"id": "8670269_1",
"entity_ids": [
"8670269_T3",
"8670269_T4"
]
}
] | [] |
7853483 | 7853483 | [
{
"id": "7853483__text",
"type": "abstract",
"text": [
"Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus. \nThe mechanisms regulating human immunodeficiency virus (HIV) persistence in human monocytes/macrophages are partially understood. Persistent HIV infection of U937 monocytic cells results in NF-kappa B activation. Whether virus-induced NF-kappa B activation is a mechanism that favors continuous viral replication in macrophages remains unknown. To further delineate the molecular mechanisms involved in the activation of NF-kappa B in HIV-infected monocytes and macrophages, we have focused on the regulation of the I kappa B molecules. First, we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in macrophages. In HIV-infected cells, I kappa B alpha protein levels are decreased secondary to enhanced protein degradation. This parallels the increased I kappa B alpha synthesis secondary to increased I kappa B alpha gene transcription, i.e., increased RNA and transcriptional activity of its promoter-enhancer. Another protein with I kappa B function, p105, is also modified in HIV-infected cells: p105 and p50 steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of p105. Transcriptional activity of p105 is also increased in infected cells and is also mediated by NF-kappa B through a specific kappa B motif. These results demonstrate the existence of a triple autoregulatory loop in monocytes and macrophages involving HIV, p105 and p50, and MAD3, with the end result of persistent NF-kappa B activation and viral persistence. Furthermore, persistent HIV infection of monocytes and macrophages provides a useful model with which to study concomitant modifications of different I kappa B molecules. "
],
"offsets": [
[
0,
1842
]
]
}
] | [
{
"id": "7853483_T1",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
14,
29
]
],
"normalized": []
},
{
"id": "7853483_T2",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
34,
38
]
],
"normalized": []
},
{
"id": "7853483_T3",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
824,
839
]
],
"normalized": []
},
{
"id": "7853483_T4",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
941,
956
]
],
"normalized": []
},
{
"id": "7853483_T5",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
990,
1005
]
],
"normalized": []
},
{
"id": "7853483_T6",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1142,
1146
]
],
"normalized": []
},
{
"id": "7853483_T7",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1188,
1192
]
],
"normalized": []
},
{
"id": "7853483_T8",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1197,
1200
]
],
"normalized": []
},
{
"id": "7853483_T9",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1308,
1312
]
],
"normalized": []
},
{
"id": "7853483_T10",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1342,
1346
]
],
"normalized": []
},
{
"id": "7853483_T11",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1568,
1572
]
],
"normalized": []
},
{
"id": "7853483_T12",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1577,
1580
]
],
"normalized": []
},
{
"id": "7853483_T13",
"type": "Protein",
"text": [
"MAD3"
],
"offsets": [
[
1586,
1590
]
],
"normalized": []
}
] | [
{
"id": "7853483_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T1"
}
]
},
{
"id": "7853483_E2",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T2"
}
]
},
{
"id": "7853483_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
859,
868
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T3"
}
]
},
{
"id": "7853483_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
980,
989
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_E5"
}
]
},
{
"id": "7853483_E5",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1011,
1024
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T5"
}
]
},
{
"id": "7853483_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1032,
1041
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T5"
}
]
},
{
"id": "7853483_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1032,
1041
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_E8"
}
]
},
{
"id": "7853483_E8",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional activity"
],
"offsets": [
[
1050,
1074
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T5"
}
]
},
{
"id": "7853483_E9",
"type": "Regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
1156,
1164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T6"
}
]
},
{
"id": "7853483_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1233,
1242
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T7"
}
]
},
{
"id": "7853483_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1233,
1242
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T8"
}
]
},
{
"id": "7853483_E12",
"type": "Transcription",
"trigger": {
"text": [
"Transcriptional activity"
],
"offsets": [
[
1314,
1338
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T10"
}
]
},
{
"id": "7853483_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1355,
1364
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_E12"
}
]
},
{
"id": "7853483_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
1395,
1403
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_E12"
}
]
},
{
"id": "7853483_E15",
"type": "Regulation",
"trigger": {
"text": [
"triple autoregulatory loop"
],
"offsets": [
[
1497,
1523
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T13"
}
]
},
{
"id": "7853483_E16",
"type": "Regulation",
"trigger": {
"text": [
"triple autoregulatory loop"
],
"offsets": [
[
1497,
1523
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T11"
}
]
},
{
"id": "7853483_E17",
"type": "Regulation",
"trigger": {
"text": [
"triple autoregulatory loop"
],
"offsets": [
[
1497,
1523
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7853483_T12"
}
]
}
] | [] | [] |
8943338 | 8943338 | [
{
"id": "8943338__text",
"type": "abstract",
"text": [
"Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene [published erratum appears in Mol Cell Biol 1997 Apr;17(4):2351] \nThe interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides -276 and -244, which contains NF-kappaB and SRE/CArG motifs. PRRII is a T-cell-specific enhancer, located between nucleotides -137 and -64, which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins. However, none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2. To find new regulatory regions of the IL-2R alpha gene, 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced. We identified an 86-nucleotide fragment that is 90% identical to the recently characterized murine IL-2-responsive element (mIL-2rE). This putative human IL-2rE, designated PRRIII, confers IL-2 responsiveness on a heterologous promoter. PRRIII contains a Stat protein binding site that overlaps with an EBS motif (GASd/EBSd). These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs. IL-2 induced the binding of Stat5a and b proteins to the human GASd element. To confirm the physiological relevance of these findings, we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element. Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor. "
],
"offsets": [
[
0,
1994
]
]
}
] | [
{
"id": "8943338_T1",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "8943338_T2",
"type": "Protein",
"text": [
"Stat5"
],
"offsets": [
[
10,
15
]
],
"normalized": []
},
{
"id": "8943338_T3",
"type": "Protein",
"text": [
"interleukin-2 receptor alpha"
],
"offsets": [
[
74,
102
]
],
"normalized": []
},
{
"id": "8943338_T4",
"type": "Protein",
"text": [
"interleukin 2 receptor alpha-chain"
],
"offsets": [
[
178,
212
]
],
"normalized": []
},
{
"id": "8943338_T5",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
214,
225
]
],
"normalized": []
},
{
"id": "8943338_T6",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
280,
291
]
],
"normalized": []
},
{
"id": "8943338_T7",
"type": "Protein",
"text": [
"Interleukin 2"
],
"offsets": [
[
369,
382
]
],
"normalized": []
},
{
"id": "8943338_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
384,
388
]
],
"normalized": []
},
{
"id": "8943338_T9",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
401,
412
]
],
"normalized": []
},
{
"id": "8943338_T10",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
493,
504
]
],
"normalized": []
},
{
"id": "8943338_T11",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
854,
859
]
],
"normalized": []
},
{
"id": "8943338_T12",
"type": "Protein",
"text": [
"HMG-I(Y)"
],
"offsets": [
[
864,
872
]
],
"normalized": []
},
{
"id": "8943338_T13",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
952,
963
]
],
"normalized": []
},
{
"id": "8943338_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
981,
985
]
],
"normalized": []
},
{
"id": "8943338_T15",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1025,
1036
]
],
"normalized": []
},
{
"id": "8943338_T16",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1090,
1101
]
],
"normalized": []
},
{
"id": "8943338_T17",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1227,
1231
]
],
"normalized": []
},
{
"id": "8943338_T18",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1317,
1321
]
],
"normalized": []
},
{
"id": "8943338_T19",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1478,
1482
]
],
"normalized": []
},
{
"id": "8943338_T20",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1506,
1509
]
],
"normalized": []
},
{
"id": "8943338_T21",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1531,
1535
]
],
"normalized": []
},
{
"id": "8943338_T22",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1747,
1758
]
],
"normalized": []
},
{
"id": "8943338_T23",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1879,
1890
]
],
"normalized": []
},
{
"id": "8943338_T24",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
1939,
1944
]
],
"normalized": []
}
] | [
{
"id": "8943338_E1",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
16,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T2"
},
{
"role": "Theme",
"ref_id": "8943338_T3"
}
]
},
{
"id": "8943338_E2",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
16,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T1"
},
{
"role": "Theme",
"ref_id": "8943338_T3"
}
]
},
{
"id": "8943338_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
316,
323
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T6"
}
]
},
{
"id": "8943338_E4",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
505,
518
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T10"
}
]
},
{
"id": "8943338_E5",
"type": "Regulation",
"trigger": {
"text": [
"controlled"
],
"offsets": [
[
539,
549
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_E4"
}
]
},
{
"id": "8943338_E6",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
816,
821
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T12"
}
]
},
{
"id": "8943338_E7",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
816,
821
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T11"
}
]
},
{
"id": "8943338_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
939,
948
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_E9"
},
{
"role": "Cause",
"ref_id": "8943338_T14"
}
]
},
{
"id": "8943338_E9",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
964,
977
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T13"
}
]
},
{
"id": "8943338_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1732,
1743
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_E11"
}
]
},
{
"id": "8943338_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1759,
1769
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T22"
}
]
},
{
"id": "8943338_E12",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
1846,
1850
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_E13"
}
]
},
{
"id": "8943338_E13",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1891,
1901
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8943338_T23"
}
]
}
] | [
{
"id": "8943338_1",
"entity_ids": [
"8943338_T7",
"8943338_T8"
]
},
{
"id": "8943338_2",
"entity_ids": [
"8943338_T4",
"8943338_T5"
]
}
] | [] |
8985116 | 8985116 | [
{
"id": "8985116__text",
"type": "abstract",
"text": [
"Sequence analysis and expression in cultured lymphocytes of the human FOSB gene (G0S3). \nG0S3 is a member of a set of putative G0/G1 switch regulatory genes (G0S genes) selected by screening cDNA libraries prepared from human blood mononuclear cells cultured for 2 hr with lectin and cycloheximide. The sequence shows high homology with the murine FOSB gene, which encodes a component of the AP1 transcriptional regulator. Comparison of cDNA and genomic sequences reveals a 4-exon structure characteristic of the FOS family of genes. Freshly isolated cells show high levels of FOSB/G0S3 and FOS/G0S7 mRNAs, which decline rapidly during incubation in culture medium. The kinetics of expression suggest that the high initial levels are caused by the isolation procedure, and do not reflect constitutive expression. In cells preincubated for a day, levels of FOS mRNA reach a maximum 20 min after the addition of lectin and decline to control levels over the next 3 hr. Levels of FOSB mRNA reach a maximum 40 min after the addition of lectin and decline to control levels over the next 6 hr. In freshly isolated cells, both FOS and FOSB mRNAs increase dramatically in response to the protein synthesis inhibitor cycloheximide. In preincubated cells, the cycloheximide response is decreased, especially in the case of FOSB. These differences in expression of FOS and FOSB suggest different roles and regulation. Regions of low base order-dependent stem-loop potential in the region of the gene are defined. These indicate where base order has been adapted for purposes other than stem-loop stability (e.g., encoding proteins or gene regulation). Regions of low potential in a 68.5-kb genomic segment containing the FOSB gene suggest that the potential may help locate genes in uncharted DNA sequences. "
],
"offsets": [
[
0,
1798
]
]
}
] | [
{
"id": "8985116_T1",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
70,
74
]
],
"normalized": []
},
{
"id": "8985116_T2",
"type": "Protein",
"text": [
"G0S3"
],
"offsets": [
[
81,
85
]
],
"normalized": []
},
{
"id": "8985116_T3",
"type": "Protein",
"text": [
"G0S3"
],
"offsets": [
[
89,
93
]
],
"normalized": []
},
{
"id": "8985116_T4",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
348,
352
]
],
"normalized": []
},
{
"id": "8985116_T5",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
577,
581
]
],
"normalized": []
},
{
"id": "8985116_T6",
"type": "Protein",
"text": [
"G0S3"
],
"offsets": [
[
582,
586
]
],
"normalized": []
},
{
"id": "8985116_T7",
"type": "Protein",
"text": [
"FOS"
],
"offsets": [
[
591,
594
]
],
"normalized": []
},
{
"id": "8985116_T8",
"type": "Protein",
"text": [
"G0S7"
],
"offsets": [
[
595,
599
]
],
"normalized": []
},
{
"id": "8985116_T9",
"type": "Protein",
"text": [
"FOS"
],
"offsets": [
[
856,
859
]
],
"normalized": []
},
{
"id": "8985116_T10",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
977,
981
]
],
"normalized": []
},
{
"id": "8985116_T11",
"type": "Protein",
"text": [
"FOS"
],
"offsets": [
[
1121,
1124
]
],
"normalized": []
},
{
"id": "8985116_T12",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
1129,
1133
]
],
"normalized": []
},
{
"id": "8985116_T13",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
1314,
1318
]
],
"normalized": []
},
{
"id": "8985116_T14",
"type": "Protein",
"text": [
"FOS"
],
"offsets": [
[
1355,
1358
]
],
"normalized": []
},
{
"id": "8985116_T15",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
1363,
1367
]
],
"normalized": []
},
{
"id": "8985116_T16",
"type": "Protein",
"text": [
"FOSB"
],
"offsets": [
[
1711,
1715
]
],
"normalized": []
}
] | [
{
"id": "8985116_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
22,
32
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T1"
}
]
},
{
"id": "8985116_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"selected"
],
"offsets": [
[
169,
177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T3"
}
]
},
{
"id": "8985116_E3",
"type": "Transcription",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
567,
573
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T5"
}
]
},
{
"id": "8985116_E4",
"type": "Transcription",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
567,
573
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T7"
}
]
},
{
"id": "8985116_E5",
"type": "Transcription",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
846,
852
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T9"
}
]
},
{
"id": "8985116_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"reach a maximum"
],
"offsets": [
[
865,
880
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_E5"
}
]
},
{
"id": "8985116_E7",
"type": "Transcription",
"trigger": {
"text": [
"Levels"
],
"offsets": [
[
967,
973
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T10"
}
]
},
{
"id": "8985116_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"reach a maximum"
],
"offsets": [
[
987,
1002
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_E7"
}
]
},
{
"id": "8985116_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1140,
1148
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T11"
}
]
},
{
"id": "8985116_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1140,
1148
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T12"
}
]
},
{
"id": "8985116_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
1277,
1286
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_E9"
}
]
},
{
"id": "8985116_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
1277,
1286
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_E10"
}
]
},
{
"id": "8985116_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1341,
1351
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T15"
}
]
},
{
"id": "8985116_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1341,
1351
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8985116_T14"
}
]
}
] | [
{
"id": "8985116_1",
"entity_ids": [
"8985116_T7",
"8985116_T8"
]
},
{
"id": "8985116_2",
"entity_ids": [
"8985116_T5",
"8985116_T6"
]
}
] | [] |
9291089 | 9291089 | [
{
"id": "9291089__text",
"type": "abstract",
"text": [
"Transcriptional regulation during myelopoiesis. \nThe coordinated production of all blood cells from a common stem cell is a highly regulated process involving successive stages of commitment and differentiation. From analyses of mice deficient in transcription factor genes and from the characterizations of chromosome breakpoints in human leukemias, it has become evident that transcription factors are important regulators of hematopoiesis. During myelopoiesis, which includes the development of granulocytic and monocytic lineages, transcription factors from several families are active, including AML1/CBF beta, C/EBP, Ets, c-Myb, HOX, and MZF-1. Few of these factors are expressed exclusively in myeloid cells; instead it appears that they cooperatively regulate transcription of myeloid-specific genes. Here we discuss recent advances in transcriptional regulation during myelopoiesis. "
],
"offsets": [
[
0,
892
]
]
}
] | [
{
"id": "9291089_T1",
"type": "Protein",
"text": [
"AML1"
],
"offsets": [
[
601,
605
]
],
"normalized": []
},
{
"id": "9291089_T2",
"type": "Protein",
"text": [
"CBF beta"
],
"offsets": [
[
606,
614
]
],
"normalized": []
},
{
"id": "9291089_T3",
"type": "Protein",
"text": [
"c-Myb"
],
"offsets": [
[
628,
633
]
],
"normalized": []
},
{
"id": "9291089_T4",
"type": "Protein",
"text": [
"MZF-1"
],
"offsets": [
[
644,
649
]
],
"normalized": []
}
] | [
{
"id": "9291089_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"active"
],
"offsets": [
[
583,
589
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T1"
}
]
},
{
"id": "9291089_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"active"
],
"offsets": [
[
583,
589
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T2"
}
]
},
{
"id": "9291089_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"active"
],
"offsets": [
[
583,
589
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T4"
}
]
},
{
"id": "9291089_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"active"
],
"offsets": [
[
583,
589
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T3"
}
]
},
{
"id": "9291089_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
676,
685
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T1"
}
]
},
{
"id": "9291089_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
676,
685
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T4"
}
]
},
{
"id": "9291089_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
676,
685
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T2"
}
]
},
{
"id": "9291089_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
676,
685
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9291089_T3"
}
]
}
] | [] | [] |
9265727 | 9265727 | [
{
"id": "9265727__text",
"type": "abstract",
"text": [
"Transcription factors in immune-mediated disease. \nA large amount of detailed information about the intracellular proteins regulating NF-kappa B activation and the cellular response to NF-kappa B activation has emerged recently. Several small molecules, an antisense oligonucleotide, and gene therapeutic agents that inhibit NF-kappa b activation have been described. Despite this, there are still significant gaps in our understanding of this process and its consequences. In contrast, the characterization of transcription factors selectively regulating cytokine production by CD4+ T cell subsets is at a very early stage. Three interacting proteins have recently been shown to contribute to subset-restricted expression of the IL-4 gene. There are other elements regulating IL-4 gene expression, however, and the relative importance of these recently identified proteins has yet to be determined. "
],
"offsets": [
[
0,
900
]
]
}
] | [
{
"id": "9265727_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
579,
582
]
],
"normalized": []
},
{
"id": "9265727_T2",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
730,
734
]
],
"normalized": []
},
{
"id": "9265727_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
777,
781
]
],
"normalized": []
}
] | [
{
"id": "9265727_E1",
"type": "Regulation",
"trigger": {
"text": [
"contribute"
],
"offsets": [
[
680,
690
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9265727_E2"
}
]
},
{
"id": "9265727_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
712,
722
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9265727_T2"
}
]
},
{
"id": "9265727_E3",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
766,
776
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9265727_E4"
}
]
},
{
"id": "9265727_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
787,
797
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9265727_T3"
}
]
}
] | [] | [] |
7961690 | 7961690 | [
{
"id": "7961690__text",
"type": "abstract",
"text": [
"Erythropoietin-dependent induction of hemoglobin synthesis in a cytokine-dependent cell line M-TAT. \nM-TAT is a cytokine-dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages. We cultured M-TAT cells long term (> 1 year) in the continuous presence of erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF). These long term cultures are referred to as M-TAT/EPO, M-TAT/GM-CSF, and M-TAT/SCF cells, respectively. Hemoglobin concentration and gamma-globin and erythroid delta-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells. When the supplemented cytokine was switched from GM-CSF to EPO, hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly (within 5 h), and the level of GATA-1 mRNA increased. In contrast, the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin, even in the presence of EPO, indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF. Thus, erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF. These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation. "
],
"offsets": [
[
0,
1326
]
]
}
] | [
{
"id": "7961690_T1",
"type": "Protein",
"text": [
"Erythropoietin"
],
"offsets": [
[
0,
14
]
],
"normalized": []
},
{
"id": "7961690_T2",
"type": "Protein",
"text": [
"erythropoietin"
],
"offsets": [
[
301,
315
]
],
"normalized": []
},
{
"id": "7961690_T3",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
317,
320
]
],
"normalized": []
},
{
"id": "7961690_T4",
"type": "Protein",
"text": [
"granulocyte-macrophage colony-stimulating factor"
],
"offsets": [
[
323,
371
]
],
"normalized": []
},
{
"id": "7961690_T5",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
373,
379
]
],
"normalized": []
},
{
"id": "7961690_T6",
"type": "Protein",
"text": [
"stem cell factor"
],
"offsets": [
[
385,
401
]
],
"normalized": []
},
{
"id": "7961690_T7",
"type": "Protein",
"text": [
"SCF"
],
"offsets": [
[
403,
406
]
],
"normalized": []
},
{
"id": "7961690_T8",
"type": "Protein",
"text": [
"erythroid delta-aminolevulinate synthase"
],
"offsets": [
[
559,
599
]
],
"normalized": []
},
{
"id": "7961690_T9",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
647,
650
]
],
"normalized": []
},
{
"id": "7961690_T10",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
671,
677
]
],
"normalized": []
},
{
"id": "7961690_T11",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
734,
740
]
],
"normalized": []
},
{
"id": "7961690_T12",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
744,
747
]
],
"normalized": []
},
{
"id": "7961690_T13",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
779,
785
]
],
"normalized": []
},
{
"id": "7961690_T14",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
841,
847
]
],
"normalized": []
},
{
"id": "7961690_T15",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
893,
899
]
],
"normalized": []
},
{
"id": "7961690_T16",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
913,
916
]
],
"normalized": []
},
{
"id": "7961690_T17",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
990,
993
]
],
"normalized": []
},
{
"id": "7961690_T18",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
1015,
1018
]
],
"normalized": []
},
{
"id": "7961690_T19",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
1073,
1079
]
],
"normalized": []
},
{
"id": "7961690_T20",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
1139,
1142
]
],
"normalized": []
},
{
"id": "7961690_T21",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
1161,
1167
]
],
"normalized": []
},
{
"id": "7961690_T22",
"type": "Protein",
"text": [
"EPO"
],
"offsets": [
[
1211,
1214
]
],
"normalized": []
}
] | [
{
"id": "7961690_E1",
"type": "Transcription",
"trigger": {
"text": [
"mRNA levels"
],
"offsets": [
[
600,
611
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7961690_T8"
}
]
},
{
"id": "7961690_E2",
"type": "Transcription",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
605,
611
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7961690_T8"
}
]
},
{
"id": "7961690_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
853,
862
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7961690_T14"
}
]
}
] | [
{
"id": "7961690_1",
"entity_ids": [
"7961690_T2",
"7961690_T3"
]
},
{
"id": "7961690_2",
"entity_ids": [
"7961690_T4",
"7961690_T5"
]
},
{
"id": "7961690_3",
"entity_ids": [
"7961690_T6",
"7961690_T7"
]
}
] | [] |
9224203 | 9224203 | [
{
"id": "9224203__text",
"type": "abstract",
"text": [
"The role of nuclear factor-kappa B in cytokine gene regulation. \nTranscription factors are DNA-binding proteins that regulate gene expression. Nuclear factor-kappa B (NF-kappa B) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as adult respiratory distress syndrome (ARDS) and sepsis syndrome. Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins (I kappa B) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells. NF-kappa B activation involves signaled phosphorylation, ubiquitination, and proteolysis of I kappa B. Liberated NF-kappa B migrates to the nucleus, where it binds to specific promoter sites and activates gene transcription. The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation. Recently, activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models. Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants, corticosteroids, and the induction of endotoxin tolerance. Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases. "
],
"offsets": [
[
0,
1488
]
]
}
] | [] | [] | [] | [] |
9686612 | 9686612 | [
{
"id": "9686612__text",
"type": "abstract",
"text": [
"Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes. \nAdhesion to extracellular matrices is known to modulate leukocyte activation, although the mechanisms are not fully understood. Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci, so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors. U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins, predominately CD11b/CD18, and to a lesser extent, CD11c/CD18. Cells stimulated with fibrinogen (10-100 microg/ml)/Mn2+ (50 microM) for 2 h were examined by electrophoretic mobility shift assay. NF-kappa B activation, minimal in unstimulated cells, was substantially up-regulated by fibrinogen. Fibrinogen also caused activation of AP-1, but not SP1 or cAMP response element-binding protein (CREB) factors. Blocking mAbs against CD18 and CD11b abrogated fibrinogen-induced NF-kappa B activation. To determine the effects on transcriptional regulation, U937 cells were transfected with a plasmid containing the HIV-1 enhancer (bearing two NF-kappa B sites) coupled to a chloramphenicol acetyltransferase (CAT) reporter. Cells were subsequently stimulated with 1) PMA for 24 h, inducing CAT activity by 2.6-fold, 2) fibrinogen/Mn2+ for 2 h, inducing CAT activity by 3.2-fold, or 3) costimulation with fibrinogen and PMA, inducing 5.7-fold the CAT activity induced by PMA alone. We conclude that contact with fibrinogen-derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18, resulting in selective activation of transcriptional regulatory factors, including NF-kappa B. "
],
"offsets": [
[
0,
1766
]
]
}
] | [
{
"id": "9686612_T1",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
568,
573
]
],
"normalized": []
},
{
"id": "9686612_T2",
"type": "Protein",
"text": [
"CD18"
],
"offsets": [
[
574,
578
]
],
"normalized": []
},
{
"id": "9686612_T3",
"type": "Protein",
"text": [
"CD11c"
],
"offsets": [
[
604,
609
]
],
"normalized": []
},
{
"id": "9686612_T4",
"type": "Protein",
"text": [
"CD18"
],
"offsets": [
[
610,
614
]
],
"normalized": []
},
{
"id": "9686612_T5",
"type": "Protein",
"text": [
"SP1"
],
"offsets": [
[
899,
902
]
],
"normalized": []
},
{
"id": "9686612_T6",
"type": "Protein",
"text": [
"CD18"
],
"offsets": [
[
982,
986
]
],
"normalized": []
},
{
"id": "9686612_T7",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
991,
996
]
],
"normalized": []
},
{
"id": "9686612_T8",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
1222,
1255
]
],
"normalized": []
},
{
"id": "9686612_T9",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1257,
1260
]
],
"normalized": []
},
{
"id": "9686612_T10",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1338,
1341
]
],
"normalized": []
},
{
"id": "9686612_T11",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1401,
1404
]
],
"normalized": []
},
{
"id": "9686612_T12",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1494,
1497
]
],
"normalized": []
},
{
"id": "9686612_T13",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
1659,
1664
]
],
"normalized": []
},
{
"id": "9686612_T14",
"type": "Protein",
"text": [
"CD18"
],
"offsets": [
[
1665,
1669
]
],
"normalized": []
}
] | [
{
"id": "9686612_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
512,
519
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T4"
}
]
},
{
"id": "9686612_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
512,
519
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T3"
}
]
},
{
"id": "9686612_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
512,
519
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T2"
}
]
},
{
"id": "9686612_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
512,
519
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T1"
}
]
},
{
"id": "9686612_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"caused"
],
"offsets": [
[
864,
870
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_E6"
}
]
},
{
"id": "9686612_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
871,
881
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T5"
}
]
},
{
"id": "9686612_E7",
"type": "Binding",
"trigger": {
"text": [
"Blocking"
],
"offsets": [
[
960,
968
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T7"
}
]
},
{
"id": "9686612_E8",
"type": "Binding",
"trigger": {
"text": [
"Blocking"
],
"offsets": [
[
960,
968
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T6"
}
]
},
{
"id": "9686612_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducing"
],
"offsets": [
[
1329,
1337
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T10"
}
]
},
{
"id": "9686612_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducing"
],
"offsets": [
[
1392,
1400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T11"
}
]
},
{
"id": "9686612_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducing"
],
"offsets": [
[
1472,
1480
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T12"
}
]
},
{
"id": "9686612_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1507,
1514
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9686612_T12"
}
]
}
] | [
{
"id": "9686612_1",
"entity_ids": [
"9686612_T8",
"9686612_T9"
]
}
] | [] |
8428000 | 8428000 | [
{
"id": "8428000__text",
"type": "abstract",
"text": [
"Interleukin-3 expression by activated T cells involves an inducible, T-cell-specific factor and an octamer binding protein. \nInterleukin-3 (IL-3) is exclusively expressed by activated T and natural killer cells, a function that is tightly controlled both in a lineage-specific and in a stimulation-dependent manner. We have investigated the protein binding characteristics and functional importance of the ACT-1-activating region of the IL-3 promoter. This region binds an inducible, T-cell-specific factor over its 5' end, a site that is necessary for the expression of IL-3 in the absence of other upstream elements. Over its 3' end, it binds a factor that is ubiquitously and constitutively expressed. This factor is Oct-1 or an immunologically related octamer-binding protein, and it plays a role in coordinating the activity of several regulatory elements. These characteristics make the ACT-1 site analogous to the activating ARRE-1 site in the IL-2 promoter. Furthermore, and despite a lack of sequence homology, the promoters of IL-3 and IL-2 share an organizational pattern of regulatory elements that is likely to be important for the T-cell-specific expression of these genes. "
],
"offsets": [
[
0,
1188
]
]
}
] | [
{
"id": "8428000_T1",
"type": "Protein",
"text": [
"Interleukin-3"
],
"offsets": [
[
0,
13
]
],
"normalized": []
},
{
"id": "8428000_T2",
"type": "Protein",
"text": [
"Interleukin-3"
],
"offsets": [
[
125,
138
]
],
"normalized": []
},
{
"id": "8428000_T3",
"type": "Protein",
"text": [
"IL-3"
],
"offsets": [
[
140,
144
]
],
"normalized": []
},
{
"id": "8428000_T4",
"type": "Protein",
"text": [
"IL-3"
],
"offsets": [
[
437,
441
]
],
"normalized": []
},
{
"id": "8428000_T5",
"type": "Protein",
"text": [
"IL-3"
],
"offsets": [
[
571,
575
]
],
"normalized": []
},
{
"id": "8428000_T6",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
720,
725
]
],
"normalized": []
},
{
"id": "8428000_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
951,
955
]
],
"normalized": []
},
{
"id": "8428000_T8",
"type": "Protein",
"text": [
"IL-3"
],
"offsets": [
[
1037,
1041
]
],
"normalized": []
},
{
"id": "8428000_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1046,
1050
]
],
"normalized": []
},
{
"id": "8428000_T13",
"type": "Entity",
"text": [
"ACT-1-activating region"
],
"offsets": [
[
406,
429
]
],
"normalized": []
},
{
"id": "8428000_T19",
"type": "Entity",
"text": [
"ARRE-1 site"
],
"offsets": [
[
932,
943
]
],
"normalized": []
}
] | [
{
"id": "8428000_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
14,
24
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T1"
}
]
},
{
"id": "8428000_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
161,
170
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T3"
}
]
},
{
"id": "8428000_E3",
"type": "Regulation",
"trigger": {
"text": [
"controlled"
],
"offsets": [
[
239,
249
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T3"
}
]
},
{
"id": "8428000_E4",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
464,
469
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T4"
},
{
"role": "Site",
"ref_id": "8428000_T13"
}
]
},
{
"id": "8428000_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
"offsets": [
[
539,
548
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_E6"
}
]
},
{
"id": "8428000_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
557,
567
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T5"
}
]
},
{
"id": "8428000_E7",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
639,
644
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T4"
},
{
"role": "Site",
"ref_id": "8428000_T13"
}
]
},
{
"id": "8428000_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"activating"
],
"offsets": [
[
921,
931
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T7"
},
{
"role": "Site",
"ref_id": "8428000_T19"
}
]
},
{
"id": "8428000_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"important"
],
"offsets": [
[
1127,
1136
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_E12"
}
]
},
{
"id": "8428000_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"important"
],
"offsets": [
[
1127,
1136
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_E11"
}
]
},
{
"id": "8428000_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1161,
1171
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T8"
}
]
},
{
"id": "8428000_E12",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1161,
1171
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8428000_T9"
}
]
}
] | [
{
"id": "8428000_1",
"entity_ids": [
"8428000_T2",
"8428000_T3"
]
}
] | [] |
2216722 | 2216722 | [
{
"id": "2216722__text",
"type": "abstract",
"text": [
"Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. \nThe 'octamer' sequence, ATGCAAAT or its complement ATTTGCAT, is a key element for the transcriptional regulation of immunoglobulin genes in B-lymphocytes as well as a number of housekeeping genes in all cell types. In lymphocytes, the octamer-binding protein Oct-2A and variants thereof are thought to contribute to the B-cell specific gene expression, while the ubiquitous protein Oct-1 seems to control general octamer site-dependent transcription. Various other genes, for example interleukin-1 and MHC class II genes, contain an octamer sequence in the promoter and are expressed in cells of both the immune and nervous systems. This prompted us to analyze the octamer-binding proteins in the latter cells. Using the electrophoretic mobility shift assay, at least six novel octamer binding proteins were detected in nuclear extracts of cultured mouse astrocytes. These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines. The nervous system-derived (N-Oct) proteins bound to the octamer DNA sequence in a manner which is indistinguishable from the Oct-1 and Oct-2A proteins. The relationship of the N-Oct proteins to Oct-1 and Oct-2A was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant Oct-1 and Oct-2A proteins. On the basis of these assays, all N-Oct-factors were found to be distinct from the ubiquitous Oct-1 and the lymphoid-specific Oct-2A proteins. In melanoma cells that contain the N-Oct-3 factor, a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an Oct-2A expression vector. We therefore speculate that N-Oct-3 and other N-Oct factors have a specific role in gene expression in cells of the nervous system. "
],
"offsets": [
[
0,
1936
]
]
}
] | [
{
"id": "2216722_T1",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
106,
111
]
],
"normalized": []
},
{
"id": "2216722_T2",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
128,
133
]
],
"normalized": []
},
{
"id": "2216722_T3",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
404,
410
]
],
"normalized": []
},
{
"id": "2216722_T4",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
527,
532
]
],
"normalized": []
},
{
"id": "2216722_T5",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
1234,
1239
]
],
"normalized": []
},
{
"id": "2216722_T6",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
1244,
1250
]
],
"normalized": []
},
{
"id": "2216722_T7",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
1303,
1308
]
],
"normalized": []
},
{
"id": "2216722_T8",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
1313,
1319
]
],
"normalized": []
},
{
"id": "2216722_T9",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
1442,
1447
]
],
"normalized": []
},
{
"id": "2216722_T10",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
1452,
1458
]
],
"normalized": []
},
{
"id": "2216722_T11",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
1563,
1568
]
],
"normalized": []
},
{
"id": "2216722_T12",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
1595,
1601
]
],
"normalized": []
},
{
"id": "2216722_T13",
"type": "Protein",
"text": [
"N-Oct-3"
],
"offsets": [
[
1647,
1654
]
],
"normalized": []
},
{
"id": "2216722_T14",
"type": "Protein",
"text": [
"Oct-2A"
],
"offsets": [
[
1778,
1784
]
],
"normalized": []
},
{
"id": "2216722_T15",
"type": "Protein",
"text": [
"N-Oct-3"
],
"offsets": [
[
1832,
1839
]
],
"normalized": []
}
] | [] | [] | [] |
2144551 | 2144551 | [
{
"id": "2144551__text",
"type": "abstract",
"text": [
"Induction of immediate early response genes by macrophage colony-stimulating factor in normal human monocytes. \nA group of coordinately induced protooncogenes, cytoskeletal, and extracellular matrix genes have been termed immediate early response genes, and their induction has been associated with growth factor-stimulated cell proliferation. We have investigated the induction of these genes by macrophage-CSF (M-CSF) in human monocytes that do not proliferate in response to M-CSF but require the factor for optimal cell differentiation. Normal human monocytes were isolated, carefully washed, and incubated for 36 to 48 h in fetal bovine serum-containing medium. At the end of this incubation the resting cells were stimulated with M-CSF, and RNA was isolated for analysis by Northern blotting. RNA from control resting cells contained low to undetectable levels of c-jun, fibronectin receptor, and actin mRNA. Within 15 to 30 min of addition of M-CSF, however, there was a dramatic coordinate induction of these genes. The c-jun gene expression was very transient and was not detectable by 60 min after M-CSF addition. In contrast, the expression of actin and fibronectin receptor mRNA was more sustained, and the expression of these genes remained elevated at 24 to 48 h after M-CSF addition. We also observed the induction of the myelomonocytic specific tyrosine kinase hck gene simultaneously with the other immediate early response genes. The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes, and in fact, super-induced the expression of c-jun and hck. Nuclear run on transcription of the c-jun, hck, and actin genes. Therefore, in normal human monocytes M-CSF induces immediate early response genes without inducing cell proliferation. These genes may then play a role in altering the physiologic status of the cells in response to CSF. "
],
"offsets": [
[
0,
1890
]
]
}
] | [
{
"id": "2144551_T1",
"type": "Protein",
"text": [
"macrophage-CSF"
],
"offsets": [
[
397,
411
]
],
"normalized": []
},
{
"id": "2144551_T2",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
413,
418
]
],
"normalized": []
},
{
"id": "2144551_T3",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
478,
483
]
],
"normalized": []
},
{
"id": "2144551_T4",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
736,
741
]
],
"normalized": []
},
{
"id": "2144551_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
870,
875
]
],
"normalized": []
},
{
"id": "2144551_T6",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
950,
955
]
],
"normalized": []
},
{
"id": "2144551_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1028,
1033
]
],
"normalized": []
},
{
"id": "2144551_T8",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
1108,
1113
]
],
"normalized": []
},
{
"id": "2144551_T9",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
1283,
1288
]
],
"normalized": []
},
{
"id": "2144551_T10",
"type": "Protein",
"text": [
"hck"
],
"offsets": [
[
1377,
1380
]
],
"normalized": []
},
{
"id": "2144551_T11",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1590,
1595
]
],
"normalized": []
},
{
"id": "2144551_T12",
"type": "Protein",
"text": [
"hck"
],
"offsets": [
[
1600,
1603
]
],
"normalized": []
},
{
"id": "2144551_T13",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1641,
1646
]
],
"normalized": []
},
{
"id": "2144551_T14",
"type": "Protein",
"text": [
"hck"
],
"offsets": [
[
1648,
1651
]
],
"normalized": []
},
{
"id": "2144551_T15",
"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
1707,
1712
]
],
"normalized": []
}
] | [
{
"id": "2144551_E1",
"type": "Transcription",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
860,
866
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T5"
}
]
},
{
"id": "2144551_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
998,
1007
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T5"
}
]
},
{
"id": "2144551_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1039,
1049
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T7"
}
]
},
{
"id": "2144551_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"after"
],
"offsets": [
[
1102,
1107
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_E3"
},
{
"role": "Cause",
"ref_id": "2144551_T8"
}
]
},
{
"id": "2144551_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1320,
1329
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T10"
}
]
},
{
"id": "2144551_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"super-induced"
],
"offsets": [
[
1558,
1571
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_E8"
}
]
},
{
"id": "2144551_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1576,
1586
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T12"
}
]
},
{
"id": "2144551_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1576,
1586
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T11"
}
]
},
{
"id": "2144551_E9",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1620,
1633
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T13"
}
]
},
{
"id": "2144551_E10",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1620,
1633
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "2144551_T14"
}
]
}
] | [
{
"id": "2144551_1",
"entity_ids": [
"2144551_T1",
"2144551_T2"
]
}
] | [] |
9322967 | 9322967 | [
{
"id": "9322967__text",
"type": "abstract",
"text": [
"Human neutrophils express GH-N gene transcripts and the pituitary transcription factor Pit-1b. \nSince GH stimulates the development and function of granulocytes, we investigated the expression of GH in granulocyte subsets. By immunocytochemistry, 25 +/- 7% of the human neutrophils were shown to express immunoreactive GH, whereas eosinophils were negative. Reversed transcription (RT)-PCR analysis demonstrated GH mRNA in neutrophils. Restriction analysis revealed that neutrophils express the GH-N gene but not the GH-V gene. Furthermore, we demonstrated by western blot analysis that neutrophils express an alternatively spliced variant of the pituitary transcription factor Pit-1, designated Pit-1b. "
],
"offsets": [
[
0,
704
]
]
}
] | [
{
"id": "9322967_T1",
"type": "Protein",
"text": [
"GH-N"
],
"offsets": [
[
26,
30
]
],
"normalized": []
},
{
"id": "9322967_T2",
"type": "Protein",
"text": [
"Pit-1b"
],
"offsets": [
[
87,
93
]
],
"normalized": []
},
{
"id": "9322967_T3",
"type": "Protein",
"text": [
"GH"
],
"offsets": [
[
102,
104
]
],
"normalized": []
},
{
"id": "9322967_T4",
"type": "Protein",
"text": [
"GH"
],
"offsets": [
[
196,
198
]
],
"normalized": []
},
{
"id": "9322967_T5",
"type": "Protein",
"text": [
"GH"
],
"offsets": [
[
319,
321
]
],
"normalized": []
},
{
"id": "9322967_T6",
"type": "Protein",
"text": [
"GH"
],
"offsets": [
[
412,
414
]
],
"normalized": []
},
{
"id": "9322967_T7",
"type": "Protein",
"text": [
"GH-N"
],
"offsets": [
[
495,
499
]
],
"normalized": []
},
{
"id": "9322967_T8",
"type": "Protein",
"text": [
"GH-V"
],
"offsets": [
[
517,
521
]
],
"normalized": []
},
{
"id": "9322967_T9",
"type": "Protein",
"text": [
"Pit-1"
],
"offsets": [
[
678,
683
]
],
"normalized": []
},
{
"id": "9322967_T10",
"type": "Protein",
"text": [
"Pit-1b"
],
"offsets": [
[
696,
702
]
],
"normalized": []
}
] | [
{
"id": "9322967_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
18,
25
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T2"
}
]
},
{
"id": "9322967_E2",
"type": "Transcription",
"trigger": {
"text": [
"express"
],
"offsets": [
[
18,
25
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T1"
}
]
},
{
"id": "9322967_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
182,
192
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T4"
}
]
},
{
"id": "9322967_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
296,
303
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T5"
}
]
},
{
"id": "9322967_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"negative"
],
"offsets": [
[
348,
356
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T5"
}
]
},
{
"id": "9322967_E6",
"type": "Transcription",
"trigger": {
"text": [
"demonstrated"
],
"offsets": [
[
399,
411
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T6"
}
]
},
{
"id": "9322967_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
483,
490
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T7"
}
]
},
{
"id": "9322967_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
483,
490
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T8"
}
]
},
{
"id": "9322967_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
599,
606
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9322967_T10"
}
]
}
] | [] | [] |
9285527 | 9285527 | [
{
"id": "9285527__text",
"type": "abstract",
"text": [
"The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha. \nThe binding of oxidized low-density lipoprotein (Ox LDL) by monocyte-macrophages causes pleiotropic effects, including changes in gene expression, and is thought to represent an early event in atherogenesis. The integral membrane glycoprotein CD36 appears to play a physiological role in binding and uptake of Ox LDL by monocyte-macrophages, although the molecular events associated with CD36-Ox LDL interaction are unknown. To approach this issue, we used CD36 transfected Chinese hampster ovary (CHO) cells, exposed them to Ox LDL, and determined changes in the activity of the transcription factor NF-kappaB. We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence following activation of CD36-producing CHO cells with the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). This enhanced DNA binding activity was inhibited by coincubation of CD36 transfected cells with the human CD36-specific antibody OKM5. We also determined that activation of NF-kappaB DNA binding activity required an intact carboxyl-terminal cytoplasmic segment on CD36. Our results support the idea that human CD36 mediates signal transduction events in response to Ox LDL. "
],
"offsets": [
[
0,
1376
]
]
}
] | [
{
"id": "9285527_T1",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
44,
48
]
],
"normalized": []
},
{
"id": "9285527_T2",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
134,
161
]
],
"normalized": []
},
{
"id": "9285527_T3",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
407,
411
]
],
"normalized": []
},
{
"id": "9285527_T4",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
552,
556
]
],
"normalized": []
},
{
"id": "9285527_T5",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
621,
625
]
],
"normalized": []
},
{
"id": "9285527_T6",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
902,
906
]
],
"normalized": []
},
{
"id": "9285527_T7",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
961,
988
]
],
"normalized": []
},
{
"id": "9285527_T8",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
990,
999
]
],
"normalized": []
},
{
"id": "9285527_T9",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
1070,
1074
]
],
"normalized": []
},
{
"id": "9285527_T10",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
1108,
1112
]
],
"normalized": []
},
{
"id": "9285527_T11",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
1266,
1270
]
],
"normalized": []
},
{
"id": "9285527_T12",
"type": "Protein",
"text": [
"CD36"
],
"offsets": [
[
1312,
1316
]
],
"normalized": []
}
] | [
{
"id": "9285527_E1",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
564,
575
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9285527_T4"
}
]
},
{
"id": "9285527_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"producing"
],
"offsets": [
[
907,
916
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9285527_T6"
}
]
}
] | [
{
"id": "9285527_1",
"entity_ids": [
"9285527_T7",
"9285527_T8"
]
}
] | [] |
8809409 | 8809409 | [
{
"id": "8809409__text",
"type": "abstract",
"text": [
"Regulation of GM-CSF gene transcription by core-binding factor. \nGM-CSF gene activation in T cells is known to involve the transcription factors nuclear factor-kappa B, AP-1, NFAT, and Sp1. Here we demonstrate that the human GM-CSF promoter and enhancer also encompass binding sites for core-binding factor (CBF). Significantly, the CBF sites are in each case contained within the minimum essential core regions required for inducible activation of transcription. Furthermore, these core regions of the enhancer and promoter each encompass closely linked binding sites for CBF, AP-1, and NFATp. The GM-CSF promoter CBF site TGTGGTCA is located 51 bp upstream of the transcription start site and also overlaps a YY-1 binding site. A 2-bp mutation within the CBF site resulted in a 2-3-fold decrease in the activities of both a 69-bp proximal promoter fragment and a 627-bp full-length promoter fragment. Stepwise deletions into the proximal promoter also revealed that the CBF site, but not the YY-1 site, was required for efficient induction of transcriptional activation. The AML1 and CBF beta genes that encode CBF each have the ability to influence cell growth and differentiation and have been implicated as proto-oncogenes in acute myeloid leukemia. This study adds GM-CSF to a growing list of cytokines and receptors that are regulated by CBF and which control the growth, differentiation, and activation of hemopoietic cells. The GM-CSF locus may represent one of several target genes that are dysregulated in acute myeloid leukemia. "
],
"offsets": [
[
0,
1541
]
]
}
] | [
{
"id": "8809409_T1",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
14,
20
]
],
"normalized": []
},
{
"id": "8809409_T2",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
65,
71
]
],
"normalized": []
},
{
"id": "8809409_T3",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
185,
188
]
],
"normalized": []
},
{
"id": "8809409_T4",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
225,
231
]
],
"normalized": []
},
{
"id": "8809409_T5",
"type": "Protein",
"text": [
"NFATp"
],
"offsets": [
[
588,
593
]
],
"normalized": []
},
{
"id": "8809409_T6",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
599,
605
]
],
"normalized": []
},
{
"id": "8809409_T7",
"type": "Protein",
"text": [
"YY-1"
],
"offsets": [
[
711,
715
]
],
"normalized": []
},
{
"id": "8809409_T8",
"type": "Protein",
"text": [
"YY-1"
],
"offsets": [
[
994,
998
]
],
"normalized": []
},
{
"id": "8809409_T9",
"type": "Protein",
"text": [
"AML1"
],
"offsets": [
[
1077,
1081
]
],
"normalized": []
},
{
"id": "8809409_T10",
"type": "Protein",
"text": [
"CBF beta"
],
"offsets": [
[
1086,
1094
]
],
"normalized": []
},
{
"id": "8809409_T11",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
1271,
1277
]
],
"normalized": []
},
{
"id": "8809409_T12",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
1437,
1443
]
],
"normalized": []
},
{
"id": "8809409_T16",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
232,
240
]
],
"normalized": []
},
{
"id": "8809409_T17",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
245,
253
]
],
"normalized": []
}
] | [
{
"id": "8809409_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_E2"
}
]
},
{
"id": "8809409_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
26,
39
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_T1"
}
]
},
{
"id": "8809409_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
77,
87
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_T2"
}
]
},
{
"id": "8809409_E4",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
269,
276
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_T4"
},
{
"role": "Site",
"ref_id": "8809409_T16"
}
]
},
{
"id": "8809409_E5",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
269,
276
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_T4"
},
{
"role": "Site",
"ref_id": "8809409_T17"
}
]
},
{
"id": "8809409_E6",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
555,
562
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_T5"
}
]
},
{
"id": "8809409_E7",
"type": "Regulation",
"trigger": {
"text": [
"dysregulated"
],
"offsets": [
[
1501,
1513
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8809409_T12"
}
]
}
] | [] | [] |
8449904 | 8449904 | [
{
"id": "8449904__text",
"type": "abstract",
"text": [
"Transcriptional regulation of the pyruvate kinase erythroid-specific promoter. \nMammal pyruvate kinases are encoded by two genes. The L gene produces the erythroid (R-PK) or the hepatic (L-PK) isozymes by the alternative use of two promoters. We report the characterization of the cis- and trans-acting elements involved in the tissue-specific activity of the L gene erythroid promoter. A R-PK DNA fragment extending from -870 to +54 relative to the cap site confers erythroid specificity to a reporter gene. Within this region, we define a minimal promoter (-62 to +54) that displays erythroid-specific activity and contains two DNA binding sites. One, located at -50, binds members of the CCACC/Sp1 family and the other, located at -20, binds the erythroid factor GATA-1. Although the -20 GATA binding site (AGATAA) is also a potential TFIID binding site, it does not bind TFIID. Furthermore, the substitution of this GATA binding site by a canonical TFIID binding site suppresses the promoter activity. Mutations and deletions of both sites indicate that only the association of CCACC/Sp1 and GATA binding sites can drive efficient and tissue-specific expression of this R-PK minimal promoter. Finally, by co-transfection experiments, we study the elements involved in the hGATA-1 transactivation of the R-PK promoter in HeLa cells. "
],
"offsets": [
[
0,
1336
]
]
}
] | [
{
"id": "8449904_T1",
"type": "Protein",
"text": [
"L"
],
"offsets": [
[
134,
135
]
],
"normalized": []
},
{
"id": "8449904_T2",
"type": "Protein",
"text": [
"R-PK"
],
"offsets": [
[
165,
169
]
],
"normalized": []
},
{
"id": "8449904_T3",
"type": "Protein",
"text": [
"L-PK"
],
"offsets": [
[
187,
191
]
],
"normalized": []
},
{
"id": "8449904_T4",
"type": "Protein",
"text": [
"L"
],
"offsets": [
[
360,
361
]
],
"normalized": []
},
{
"id": "8449904_T5",
"type": "Protein",
"text": [
"R-PK"
],
"offsets": [
[
389,
393
]
],
"normalized": []
},
{
"id": "8449904_T6",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
766,
772
]
],
"normalized": []
},
{
"id": "8449904_T7",
"type": "Protein",
"text": [
"R-PK"
],
"offsets": [
[
1174,
1178
]
],
"normalized": []
},
{
"id": "8449904_T8",
"type": "Protein",
"text": [
"hGATA-1"
],
"offsets": [
[
1276,
1283
]
],
"normalized": []
},
{
"id": "8449904_T9",
"type": "Protein",
"text": [
"R-PK"
],
"offsets": [
[
1307,
1311
]
],
"normalized": []
},
{
"id": "8449904_T13",
"type": "Entity",
"text": [
"erythroid promoter"
],
"offsets": [
[
367,
385
]
],
"normalized": []
},
{
"id": "8449904_T18",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1312,
1320
]
],
"normalized": []
}
] | [
{
"id": "8449904_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"produces"
],
"offsets": [
[
141,
149
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_T3"
}
]
},
{
"id": "8449904_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"by the alternative use of"
],
"offsets": [
[
202,
227
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_E1"
}
]
},
{
"id": "8449904_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activity"
],
"offsets": [
[
344,
352
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_T4"
},
{
"role": "Site",
"ref_id": "8449904_T13"
}
]
},
{
"id": "8449904_E4",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
739,
744
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_T6"
}
]
},
{
"id": "8449904_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"drive"
],
"offsets": [
[
1119,
1124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_E6"
}
]
},
{
"id": "8449904_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1155,
1165
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_T7"
}
]
},
{
"id": "8449904_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
1284,
1299
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8449904_T9"
},
{
"role": "Cause",
"ref_id": "8449904_T8"
},
{
"role": "Site",
"ref_id": "8449904_T18"
}
]
}
] | [] | [] |
1829648 | 1829648 | [
{
"id": "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": "1829648_T1",
"type": "Protein",
"text": [
"MAD-3"
],
"offsets": [
[
261,
266
]
],
"normalized": []
},
{
"id": "1829648_T2",
"type": "Protein",
"text": [
"KBF1"
],
"offsets": [
[
477,
481
]
],
"normalized": []
},
{
"id": "1829648_T3",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
482,
485
]
],
"normalized": []
},
{
"id": "1829648_T4",
"type": "Protein",
"text": [
"MAD-3"
],
"offsets": [
[
576,
581
]
],
"normalized": []
},
{
"id": "1829648_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
656,
659
]
],
"normalized": []
},
{
"id": "1829648_T6",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
660,
663
]
],
"normalized": []
},
{
"id": "1829648_T7",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
703,
706
]
],
"normalized": []
},
{
"id": "1829648_T8",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
707,
710
]
],
"normalized": []
},
{
"id": "1829648_T9",
"type": "Protein",
"text": [
"KBF1"
],
"offsets": [
[
711,
715
]
],
"normalized": []
},
{
"id": "1829648_T10",
"type": "Protein",
"text": [
"MAD-3"
],
"offsets": [
[
761,
766
]
],
"normalized": []
}
] | [
{
"id": "1829648_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
240,
247
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_T1"
}
]
},
{
"id": "1829648_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
616,
623
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_E6"
}
]
},
{
"id": "1829648_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
616,
623
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_E5"
}
]
},
{
"id": "1829648_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
616,
623
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_E7"
}
]
},
{
"id": "1829648_E5",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
632,
648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_T6"
}
]
},
{
"id": "1829648_E6",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
632,
648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_T7"
}
]
},
{
"id": "1829648_E7",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
632,
648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1829648_T5"
}
]
}
] | [
{
"id": "1829648_1",
"entity_ids": [
"1829648_T7",
"1829648_T8",
"1829648_T9"
]
},
{
"id": "1829648_2",
"entity_ids": [
"1829648_T2",
"1829648_T3"
]
}
] | [] |
1314139 | 1314139 | [
{
"id": "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": "1314139_T1",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
146,
151
]
],
"normalized": []
},
{
"id": "1314139_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
156,
161
]
],
"normalized": []
},
{
"id": "1314139_T3",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
303,
308
]
],
"normalized": []
},
{
"id": "1314139_T4",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
313,
318
]
],
"normalized": []
},
{
"id": "1314139_T5",
"type": "Protein",
"text": [
"Interferon gamma"
],
"offsets": [
[
356,
372
]
],
"normalized": []
},
{
"id": "1314139_T6",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
392,
397
]
],
"normalized": []
},
{
"id": "1314139_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
409,
414
]
],
"normalized": []
},
{
"id": "1314139_T8",
"type": "Protein",
"text": [
"Tumor necrosis factor"
],
"offsets": [
[
424,
445
]
],
"normalized": []
},
{
"id": "1314139_T9",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
463,
468
]
],
"normalized": []
},
{
"id": "1314139_T10",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
497,
502
]
],
"normalized": []
}
] | [
{
"id": "1314139_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"Activation"
],
"offsets": [
[
80,
90
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E4"
}
]
},
{
"id": "1314139_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"Activation"
],
"offsets": [
[
80,
90
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E3"
}
]
},
{
"id": "1314139_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
94,
104
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T1"
}
]
},
{
"id": "1314139_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
94,
104
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T2"
}
]
},
{
"id": "1314139_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
281,
288
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E7"
}
]
},
{
"id": "1314139_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
281,
288
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E8"
}
]
},
{
"id": "1314139_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
319,
329
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T3"
}
]
},
{
"id": "1314139_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
319,
329
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T4"
}
]
},
{
"id": "1314139_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
373,
382
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T7"
},
{
"role": "Cause",
"ref_id": "1314139_T5"
}
]
},
{
"id": "1314139_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
373,
382
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T6"
},
{
"role": "Cause",
"ref_id": "1314139_T5"
}
]
},
{
"id": "1314139_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
446,
453
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T9"
},
{
"role": "Cause",
"ref_id": "1314139_T8"
}
]
},
{
"id": "1314139_E12",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
487,
493
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_T10"
},
{
"role": "Cause",
"ref_id": "1314139_T8"
}
]
},
{
"id": "1314139_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
620,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E11"
}
]
},
{
"id": "1314139_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
620,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E5"
}
]
},
{
"id": "1314139_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
620,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E9"
}
]
},
{
"id": "1314139_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
620,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E6"
}
]
},
{
"id": "1314139_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
620,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E12"
}
]
},
{
"id": "1314139_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
620,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1314139_E10"
}
]
}
] | [] | [] |
9175835 | 9175835 | [
{
"id": "9175835__text",
"type": "abstract",
"text": [
"Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. \nTip of herpesvirus saimiri associates with Lck and down-regulates Lck-mediated activation. We identified a novel cellular Tip-associated protein (Tap) by a yeast two-hybrid screen. Tap associated with Tip following transient expression in COS-1 cells and stable expression in human Jurkat-T cells. Expression of Tip and Tap in Jurkat-T cells induced dramatic cell aggregation. Aggregation was likely caused by the up-regulated surface expression of adhesion molecules including integrin alpha, L-selectin, ICAM-3, and H-CAM. Furthermore, NF-kappaB transcriptional factor of aggregated cells had approximately 40-fold higher activity than that of parental cells. Thus, Tap is likely to be an important cellular mediator of Tip function in T cell transformation by herpesvirus saimiri. "
],
"offsets": [
[
0,
898
]
]
}
] | [
{
"id": "9175835_T1",
"type": "Protein",
"text": [
"Lck"
],
"offsets": [
[
157,
160
]
],
"normalized": []
},
{
"id": "9175835_T2",
"type": "Protein",
"text": [
"Lck"
],
"offsets": [
[
180,
183
]
],
"normalized": []
},
{
"id": "9175835_T3",
"type": "Protein",
"text": [
"L-selectin"
],
"offsets": [
[
608,
618
]
],
"normalized": []
},
{
"id": "9175835_T4",
"type": "Protein",
"text": [
"ICAM-3"
],
"offsets": [
[
620,
626
]
],
"normalized": []
},
{
"id": "9175835_T5",
"type": "Protein",
"text": [
"H-CAM"
],
"offsets": [
[
632,
637
]
],
"normalized": []
}
] | [
{
"id": "9175835_E1",
"type": "Binding",
"trigger": {
"text": [
"associates"
],
"offsets": [
[
141,
151
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_T1"
}
]
},
{
"id": "9175835_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulated"
],
"offsets": [
[
528,
540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_E7"
}
]
},
{
"id": "9175835_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulated"
],
"offsets": [
[
528,
540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_E6"
}
]
},
{
"id": "9175835_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulated"
],
"offsets": [
[
528,
540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_E5"
}
]
},
{
"id": "9175835_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
549,
559
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_T5"
}
]
},
{
"id": "9175835_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
549,
559
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_T3"
}
]
},
{
"id": "9175835_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
549,
559
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9175835_T4"
}
]
}
] | [] | [] |
9058790 | 9058790 | [
{
"id": "9058790__text",
"type": "abstract",
"text": [
"Nuclear Rel-A and c-Rel protein complexes are differentially distributed within human thymocytes. \nNuclear factor-kappa B (NF-kappa B)/Rel proteins are inducible transcriptional regulators of numerous cellular genes. They are particularly abundant in lymphoid tissues and are thought to be critical for the transcription of genes involved in immune and inflammatory responses. We have reported previously that a nuclear NF-kappa B activity was present in freshly extracted human thymocytes in the absence of in vitro treatment of these cells. In the present report, we identified NF-kappa B proteins extracted from human thymocyte nuclei as being p50/p65 and p50/c-Rel complexes. Immunochemical and immunofluorescent staining of thymus sections using specific Abs allowed visualization of nuclear NF-kappa B proteins in both thymocytes and nonthymocyte cells. This detection suggested a preferential activation of p50/c-Rel in medullary thymocytes, whereas p50/p65 was present in both cortical and medullary regions of human thymus lobules. However, the intensity of p65 labeling was much higher in several thymocytes from the medulla. p65, p50, and c-Rel activities were found in both CD4- and CD8-positive thymocytes. These observations suggest that p65 and c-Rel complexes play distinct roles in gene expression and that both forms of NF-kappa B play critical roles during late stages of the intrathymic maturation of T cells. "
],
"offsets": [
[
0,
1430
]
]
}
] | [
{
"id": "9058790_T1",
"type": "Protein",
"text": [
"Rel-A"
],
"offsets": [
[
8,
13
]
],
"normalized": []
},
{
"id": "9058790_T2",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
18,
23
]
],
"normalized": []
},
{
"id": "9058790_T3",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
647,
650
]
],
"normalized": []
},
{
"id": "9058790_T4",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
651,
654
]
],
"normalized": []
},
{
"id": "9058790_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
659,
662
]
],
"normalized": []
},
{
"id": "9058790_T6",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
663,
668
]
],
"normalized": []
},
{
"id": "9058790_T7",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
914,
917
]
],
"normalized": []
},
{
"id": "9058790_T8",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
918,
923
]
],
"normalized": []
},
{
"id": "9058790_T9",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
957,
960
]
],
"normalized": []
},
{
"id": "9058790_T10",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
961,
964
]
],
"normalized": []
},
{
"id": "9058790_T11",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1067,
1070
]
],
"normalized": []
},
{
"id": "9058790_T12",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1136,
1139
]
],
"normalized": []
},
{
"id": "9058790_T13",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1141,
1144
]
],
"normalized": []
},
{
"id": "9058790_T14",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1150,
1155
]
],
"normalized": []
},
{
"id": "9058790_T15",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1186,
1189
]
],
"normalized": []
},
{
"id": "9058790_T16",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1252,
1255
]
],
"normalized": []
},
{
"id": "9058790_T17",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1260,
1265
]
],
"normalized": []
},
{
"id": "9058790_T18",
"type": "Entity",
"text": [
"Nuclear"
],
"offsets": [
[
0,
7
]
],
"normalized": []
}
] | [
{
"id": "9058790_E1",
"type": "Localization",
"trigger": {
"text": [
"distributed"
],
"offsets": [
[
61,
72
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T2"
},
{
"role": "AtLoc",
"ref_id": "9058790_T18"
}
]
},
{
"id": "9058790_E2",
"type": "Localization",
"trigger": {
"text": [
"distributed"
],
"offsets": [
[
61,
72
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T1"
},
{
"role": "AtLoc",
"ref_id": "9058790_T18"
}
]
},
{
"id": "9058790_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
900,
910
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T8"
}
]
},
{
"id": "9058790_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
900,
910
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T7"
}
]
},
{
"id": "9058790_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"present"
],
"offsets": [
[
969,
976
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T10"
}
]
},
{
"id": "9058790_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"present"
],
"offsets": [
[
969,
976
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T9"
}
]
},
{
"id": "9058790_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"higher"
],
"offsets": [
[
1089,
1095
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T11"
}
]
},
{
"id": "9058790_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"found"
],
"offsets": [
[
1172,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T12"
}
]
},
{
"id": "9058790_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"found"
],
"offsets": [
[
1172,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T14"
}
]
},
{
"id": "9058790_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"found"
],
"offsets": [
[
1172,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9058790_T13"
}
]
}
] | [] | [] |
9724088 | 9724088 | [
{
"id": "9724088__text",
"type": "abstract",
"text": [
"Peripheral T lymphocytes from women with breast cancer exhibit abnormal protein expression of several signaling molecules. \nWe examined signaling molecules of peripheral blood T lymphocytes obtained from women with breast cancer. In 6 of 14 patients, T lymphocytes displayed an impaired ability to translocate NFeB p65 (Rel-A) following activation by anti-CD3 and IL-2. This observation was made despite normal cytoplasmic levels of the Rel-A protein. We also detected abnormally low levels of the signaling molecules T-cell receptor (TCR)-zeta, ZAP-70 and p56lck in 4 of 14 breast cancer patients, i.e., defects in T-cell signaling molecules. T lymphocytes from 6 of the 14 patients also exhibited an increased expression of the dual specificity phosphatase, map kinase phosphatase-1 (MKP-1). MKP-1 inactivates MAP kinase and therefore may interfere with the activation of c-jun and c-fos. Abnormalities of I or more signaling molecules were found in 9 of 14 patients; however, only 3 patients had T cells that exhibited all 5 defects. Our data have implications for the detection of potentially dysfunctional T cells in patients with cancer. For example, the analysis of only 1 signaling molecule may allow patients with significant defects in T-cell signaling to go unnoticed. Finally, despite impaired Rel-A translocation, T cells were capable of transcribing IL-2. Impairments in the translocation of Rel-B and c-Rel further suggest that the NFKB family members Rel-A, Rel-B and c-Rel are not required for the transcription of IL-2 in the peripheral T lymphocytes of patients with breast cancer. "
],
"offsets": [
[
0,
1601
]
]
}
] | [
{
"id": "9724088_T1",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
315,
318
]
],
"normalized": []
},
{
"id": "9724088_T2",
"type": "Protein",
"text": [
"Rel-A"
],
"offsets": [
[
320,
325
]
],
"normalized": []
},
{
"id": "9724088_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
364,
368
]
],
"normalized": []
},
{
"id": "9724088_T4",
"type": "Protein",
"text": [
"Rel-A"
],
"offsets": [
[
437,
442
]
],
"normalized": []
},
{
"id": "9724088_T5",
"type": "Protein",
"text": [
"T-cell receptor (TCR)-zeta"
],
"offsets": [
[
518,
544
]
],
"normalized": []
},
{
"id": "9724088_T6",
"type": "Protein",
"text": [
"ZAP-70"
],
"offsets": [
[
546,
552
]
],
"normalized": []
},
{
"id": "9724088_T7",
"type": "Protein",
"text": [
"p56lck"
],
"offsets": [
[
557,
563
]
],
"normalized": []
},
{
"id": "9724088_T8",
"type": "Protein",
"text": [
"map kinase phosphatase-1"
],
"offsets": [
[
760,
784
]
],
"normalized": []
},
{
"id": "9724088_T9",
"type": "Protein",
"text": [
"MKP-1"
],
"offsets": [
[
786,
791
]
],
"normalized": []
},
{
"id": "9724088_T10",
"type": "Protein",
"text": [
"MKP-1"
],
"offsets": [
[
794,
799
]
],
"normalized": []
},
{
"id": "9724088_T11",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
874,
879
]
],
"normalized": []
},
{
"id": "9724088_T12",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
884,
889
]
],
"normalized": []
},
{
"id": "9724088_T13",
"type": "Protein",
"text": [
"Rel-A"
],
"offsets": [
[
1306,
1311
]
],
"normalized": []
},
{
"id": "9724088_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1364,
1368
]
],
"normalized": []
},
{
"id": "9724088_T15",
"type": "Protein",
"text": [
"Rel-B"
],
"offsets": [
[
1406,
1411
]
],
"normalized": []
},
{
"id": "9724088_T16",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1416,
1421
]
],
"normalized": []
},
{
"id": "9724088_T17",
"type": "Protein",
"text": [
"Rel-A"
],
"offsets": [
[
1467,
1472
]
],
"normalized": []
},
{
"id": "9724088_T18",
"type": "Protein",
"text": [
"Rel-B"
],
"offsets": [
[
1474,
1479
]
],
"normalized": []
},
{
"id": "9724088_T19",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1484,
1489
]
],
"normalized": []
},
{
"id": "9724088_T20",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1532,
1536
]
],
"normalized": []
}
] | [
{
"id": "9724088_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"impaired"
],
"offsets": [
[
278,
286
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E3"
}
]
},
{
"id": "9724088_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"impaired"
],
"offsets": [
[
278,
286
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E4"
}
]
},
{
"id": "9724088_E3",
"type": "Localization",
"trigger": {
"text": [
"translocate"
],
"offsets": [
[
298,
309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T2"
}
]
},
{
"id": "9724088_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"following"
],
"offsets": [
[
327,
336
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E3"
}
]
},
{
"id": "9724088_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
423,
429
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T4"
}
]
},
{
"id": "9724088_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"abnormally low levels"
],
"offsets": [
[
469,
490
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T7"
}
]
},
{
"id": "9724088_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"abnormally low levels"
],
"offsets": [
[
469,
490
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T6"
}
]
},
{
"id": "9724088_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"abnormally low levels"
],
"offsets": [
[
469,
490
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T5"
}
]
},
{
"id": "9724088_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
702,
711
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E10"
}
]
},
{
"id": "9724088_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
712,
722
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T9"
}
]
},
{
"id": "9724088_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"interfere"
],
"offsets": [
[
841,
850
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E13"
}
]
},
{
"id": "9724088_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"interfere"
],
"offsets": [
[
841,
850
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E14"
}
]
},
{
"id": "9724088_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
860,
870
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T12"
}
]
},
{
"id": "9724088_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
860,
870
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T11"
}
]
},
{
"id": "9724088_E15",
"type": "Negative_regulation",
"trigger": {
"text": [
"despite"
],
"offsets": [
[
1289,
1296
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E18"
},
{
"role": "Cause",
"ref_id": "9724088_E16"
}
]
},
{
"id": "9724088_E16",
"type": "Negative_regulation",
"trigger": {
"text": [
"impaired"
],
"offsets": [
[
1297,
1305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E17"
}
]
},
{
"id": "9724088_E17",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1312,
1325
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T13"
}
]
},
{
"id": "9724088_E18",
"type": "Transcription",
"trigger": {
"text": [
"transcribing"
],
"offsets": [
[
1351,
1363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T14"
}
]
},
{
"id": "9724088_E19",
"type": "Negative_regulation",
"trigger": {
"text": [
"Impairments"
],
"offsets": [
[
1370,
1381
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E22"
}
]
},
{
"id": "9724088_E20",
"type": "Negative_regulation",
"trigger": {
"text": [
"Impairments"
],
"offsets": [
[
1370,
1381
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E21"
}
]
},
{
"id": "9724088_E21",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1389,
1402
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T16"
}
]
},
{
"id": "9724088_E22",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1389,
1402
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T15"
}
]
},
{
"id": "9724088_E23",
"type": "Regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
1498,
1506
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E26"
},
{
"role": "Cause",
"ref_id": "9724088_T17"
}
]
},
{
"id": "9724088_E24",
"type": "Regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
1498,
1506
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E26"
},
{
"role": "Cause",
"ref_id": "9724088_T18"
}
]
},
{
"id": "9724088_E25",
"type": "Regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
1498,
1506
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_E26"
},
{
"role": "Cause",
"ref_id": "9724088_T19"
}
]
},
{
"id": "9724088_E26",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1515,
1528
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9724088_T20"
}
]
}
] | [
{
"id": "9724088_1",
"entity_ids": [
"9724088_T1",
"9724088_T2"
]
},
{
"id": "9724088_2",
"entity_ids": [
"9724088_T8",
"9724088_T9"
]
}
] | [] |
9690455 | 9690455 | [
{
"id": "9690455__text",
"type": "abstract",
"text": [
"Ex vivo activation of tumor-draining lymph node T cells reverses defects in signal transduction molecules. \nThe adoptive transfer of tumor-draining lymph node (LN) T cells activated ex vivo with anti-CD3 and interleukin 2 (IL-2) mediates the regression of the poorly immunogenic murine melanoma D5. The efficacy of the activated LN cells is augmented when the sensitizing tumor is a genetically modified variant (designated D5G6) that secretes granulocyte/macrophage-colony-stimulating factor. In contrast to anti-CD3/IL-2-activated LN cells, adoptive transfer of freshly isolated tumor-draining LN T cells has no therapeutic activity. To determine whether the acquisition of antitumor function during ex vivo activation is associated with modifications in signal transduction capacity, the protein tyrosine kinases p56lck and p59fyn and proteins of the NF-kappaB family were analyzed in tumor-draining LN T cells. The levels of p56lck and p59fyn were lower in tumor-draining than in normal LN T cells and production of tyrosine-phosphorylated substrates was markedly depressed following anti-CD3 stimulation. After 5-day anti-CD3/IL-2 activation, levels of p56lck and p59fyn and protein tyrosine kinase activity increased. Interestingly, the levels of p56lck, p59fyn, and tyrosine kinase activity were higher in activated T cells derived from LN that drained D5G6 than they were in those from D5 tumors. In contrast, the cytoplasmic levels of c-Rel and Rel A were normal in freshly isolated tumor-draining LN, as was nuclear kappaB DNA-binding activity induced by anti-CD3 mAb or phorbol myristate acetate. Stimulation of activated LN cells with D5 tumor cells induced the nuclear translocation of NF-kappaB. These findings indicate that the recovery of proteins mediating signal transduction through the T cell receptor/CD3 complex in LN T cells activated ex vivo was associated with the acquisition of antitumor function. "
],
"offsets": [
[
0,
1925
]
]
}
] | [
{
"id": "9690455_T1",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
208,
221
]
],
"normalized": []
},
{
"id": "9690455_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
223,
227
]
],
"normalized": []
},
{
"id": "9690455_T3",
"type": "Protein",
"text": [
"granulocyte/macrophage-colony-stimulating factor"
],
"offsets": [
[
444,
492
]
],
"normalized": []
},
{
"id": "9690455_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
518,
522
]
],
"normalized": []
},
{
"id": "9690455_T5",
"type": "Protein",
"text": [
"p56lck"
],
"offsets": [
[
816,
822
]
],
"normalized": []
},
{
"id": "9690455_T6",
"type": "Protein",
"text": [
"p59fyn"
],
"offsets": [
[
827,
833
]
],
"normalized": []
},
{
"id": "9690455_T7",
"type": "Protein",
"text": [
"p56lck"
],
"offsets": [
[
929,
935
]
],
"normalized": []
},
{
"id": "9690455_T8",
"type": "Protein",
"text": [
"p59fyn"
],
"offsets": [
[
940,
946
]
],
"normalized": []
},
{
"id": "9690455_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1131,
1135
]
],
"normalized": []
},
{
"id": "9690455_T10",
"type": "Protein",
"text": [
"p56lck"
],
"offsets": [
[
1158,
1164
]
],
"normalized": []
},
{
"id": "9690455_T11",
"type": "Protein",
"text": [
"p59fyn"
],
"offsets": [
[
1169,
1175
]
],
"normalized": []
},
{
"id": "9690455_T12",
"type": "Protein",
"text": [
"p56lck"
],
"offsets": [
[
1253,
1259
]
],
"normalized": []
},
{
"id": "9690455_T13",
"type": "Protein",
"text": [
"p59fyn"
],
"offsets": [
[
1261,
1267
]
],
"normalized": []
},
{
"id": "9690455_T14",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1444,
1449
]
],
"normalized": []
},
{
"id": "9690455_T15",
"type": "Protein",
"text": [
"Rel A"
],
"offsets": [
[
1454,
1459
]
],
"normalized": []
}
] | [
{
"id": "9690455_E1",
"type": "Localization",
"trigger": {
"text": [
"secretes"
],
"offsets": [
[
435,
443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T3"
}
]
},
{
"id": "9690455_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"analyzed"
],
"offsets": [
[
876,
884
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T6"
}
]
},
{
"id": "9690455_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"analyzed"
],
"offsets": [
[
876,
884
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T5"
}
]
},
{
"id": "9690455_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
919,
925
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T8"
}
]
},
{
"id": "9690455_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
919,
925
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T7"
}
]
},
{
"id": "9690455_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1148,
1154
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T11"
}
]
},
{
"id": "9690455_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1148,
1154
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T10"
}
]
},
{
"id": "9690455_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1213,
1222
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_E7"
}
]
},
{
"id": "9690455_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1213,
1222
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_E6"
}
]
},
{
"id": "9690455_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1243,
1249
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T13"
}
]
},
{
"id": "9690455_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1243,
1249
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T12"
}
]
},
{
"id": "9690455_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"higher"
],
"offsets": [
[
1303,
1309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_E11"
}
]
},
{
"id": "9690455_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"higher"
],
"offsets": [
[
1303,
1309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_E10"
}
]
},
{
"id": "9690455_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1434,
1440
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T14"
}
]
},
{
"id": "9690455_E15",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1434,
1440
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9690455_T15"
}
]
}
] | [
{
"id": "9690455_1",
"entity_ids": [
"9690455_T1",
"9690455_T2"
]
}
] | [] |
7927175 | 7927175 | [
{
"id": "7927175__text",
"type": "abstract",
"text": [
"[An overexpression of retinoic acid receptor alpha blocks myeloid cell differentiation at the promyelocyte stage] \nRetinoic acid (RA), a vitamin A derivative, exerts a wide range of biological effects related to cell proliferation and differentiation. The pleiotropic effects of RA are thought to be mediated through specific nuclear RA receptors (RARs). RARs are members of the steroid/thyroid hormone receptor superfamily and exhibit a molecular structure that possess discrete DNA-binding and RA (ligand)-binding domains. In hematopoietic system, RA and RARs, predominantly RAR alpha may play key roles for the proliferation and differentiation of hematopoietic progenitors. However, it is currently unknown how RA and RARs are involved in regulating normal hematopoietic differentiation. To make clear the roles of RA and RAR alpha in the normal hematopoiesis, I have introduced the construct of human RAR alpha (hRAR alpha) into murine bone marrow cells with retroviral vector, and selected infected cells with drug resistant marker (Neo(r)) cultured on the stroma cell line (PA6-neo), and analyzed the behavior of infected cells. All of procedure were done in vitro. Most cells infected with hRAR alpha exhibited promyelocytic morphology and were thought to be blocked at the promyelocytic stage in their myeloid differentiation. Furthermore, these immature cells differentiated terminally into mature granulocytes by adding with RA (10(-6) M). RAR alpha infected cells were also able to differentiate into mature macrophages in the both of long term culture and IL3 colony. These observations suggest that an overexpression of RAR alpha alone is effective to suppress myeloid cell differentiation and RAR alpha plays a crucial role in the terminal differentiation of myeloid precursors. The system described here may serve as a model for studying the the essential genes for differentiation of normal bone marrow cells. "
],
"offsets": [
[
0,
1927
]
]
}
] | [
{
"id": "7927175_T1",
"type": "Protein",
"text": [
"retinoic acid receptor alpha"
],
"offsets": [
[
22,
50
]
],
"normalized": []
},
{
"id": "7927175_T2",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
577,
586
]
],
"normalized": []
},
{
"id": "7927175_T3",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
826,
835
]
],
"normalized": []
},
{
"id": "7927175_T4",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
906,
915
]
],
"normalized": []
},
{
"id": "7927175_T5",
"type": "Protein",
"text": [
"hRAR alpha"
],
"offsets": [
[
917,
927
]
],
"normalized": []
},
{
"id": "7927175_T6",
"type": "Protein",
"text": [
"hRAR alpha"
],
"offsets": [
[
1198,
1208
]
],
"normalized": []
},
{
"id": "7927175_T7",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
1451,
1460
]
],
"normalized": []
},
{
"id": "7927175_T8",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
1634,
1643
]
],
"normalized": []
},
{
"id": "7927175_T9",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
1708,
1717
]
],
"normalized": []
}
] | [
{
"id": "7927175_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
4,
18
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7927175_E2"
}
]
},
{
"id": "7927175_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
4,
18
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7927175_T1"
}
]
},
{
"id": "7927175_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1616,
1630
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7927175_T8"
}
]
},
{
"id": "7927175_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1616,
1630
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7927175_E3"
}
]
}
] | [
{
"id": "7927175_1",
"entity_ids": [
"7927175_T4",
"7927175_T5"
]
}
] | [] |
8702849 | 8702849 | [
{
"id": "8702849__text",
"type": "abstract",
"text": [
"Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc [published erratum appears in J Biol Chem 1996 Dec 27;271(52):33705] \nThe cyclosporin A (CsA)/FK506-sensitive nuclear factor of activated T cells (NFAT) plays a key role in the inducible expression of cytokine genes in T cells. Although NFAT has been recently shown to be inducible in several non-T immune cells, the NFAT gene family members characterized to date have been isolated only from T cells. To further characterize NFAT function in human B cells and to demonstrate cytokine gene specificity of NFAT proteins, we report here the isolation and characterization of a cDNA clone from the Raji B cell line. The cDNA clone encodes a new isoform, NFATc.beta, of the NFAT gene family member NFATc (designated here NFATc.alpha). The amino acid sequence of NFATc.beta differs from that of NFATc.alpha in the first NH2-terminal 29 residues and contains an additional region of 142 residues at the COOH terminus. Northern analysis using a probe encompassing a common region of both isoforms showed two mRNA species of 2.7 and 4.5 kilobase pairs, while an NFATc.beta-specific probe detected only the 4.5-kilobase pair mRNA which was preferentially expressed in the spleen. Transient expression of NFATc.beta was capable of activating an interleukin-2 NFAT-driven reporter gene in stimulated Jurkat cells in a CsA-sensitive manner. However, NFATc.beta neither bound to the kappa3 element ( an NFAT-binding site ) in the tumor necrosis factor-alpha promoter nor activated the tumor necrosis factor-alpha promoter in cotransfection assays. These data suggest that different members or isoforms of NFAT gene family may regulate inducible expression of different cytokine genes. "
],
"offsets": [
[
0,
1781
]
]
}
] | [
{
"id": "8702849_T1",
"type": "Protein",
"text": [
"NFATc"
],
"offsets": [
[
103,
108
]
],
"normalized": []
},
{
"id": "8702849_T2",
"type": "Protein",
"text": [
"NFATc.beta"
],
"offsets": [
[
760,
770
]
],
"normalized": []
},
{
"id": "8702849_T3",
"type": "Protein",
"text": [
"NFATc"
],
"offsets": [
[
803,
808
]
],
"normalized": []
},
{
"id": "8702849_T4",
"type": "Protein",
"text": [
"NFATc.alpha"
],
"offsets": [
[
826,
837
]
],
"normalized": []
},
{
"id": "8702849_T5",
"type": "Protein",
"text": [
"NFATc.beta"
],
"offsets": [
[
867,
877
]
],
"normalized": []
},
{
"id": "8702849_T6",
"type": "Protein",
"text": [
"NFATc.alpha"
],
"offsets": [
[
899,
910
]
],
"normalized": []
},
{
"id": "8702849_T7",
"type": "Protein",
"text": [
"NFATc.beta"
],
"offsets": [
[
1163,
1173
]
],
"normalized": []
},
{
"id": "8702849_T8",
"type": "Protein",
"text": [
"NFATc.beta"
],
"offsets": [
[
1304,
1314
]
],
"normalized": []
},
{
"id": "8702849_T9",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
1344,
1357
]
],
"normalized": []
},
{
"id": "8702849_T10",
"type": "Protein",
"text": [
"NFATc.beta"
],
"offsets": [
[
1447,
1457
]
],
"normalized": []
},
{
"id": "8702849_T11",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
1526,
1553
]
],
"normalized": []
},
{
"id": "8702849_T12",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
1581,
1608
]
],
"normalized": []
},
{
"id": "8702849_T15",
"type": "Entity",
"text": [
"kappa3 element"
],
"offsets": [
[
1479,
1493
]
],
"normalized": []
},
{
"id": "8702849_T17",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1609,
1617
]
],
"normalized": []
}
] | [
{
"id": "8702849_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1290,
1300
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8702849_T8"
}
]
},
{
"id": "8702849_E2",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
1466,
1471
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8702849_T10"
},
{
"role": "Theme",
"ref_id": "8702849_T11"
},
{
"role": "Site",
"ref_id": "8702849_T15"
}
]
},
{
"id": "8702849_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1567,
1576
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8702849_T12"
},
{
"role": "Cause",
"ref_id": "8702849_T10"
},
{
"role": "Site",
"ref_id": "8702849_T17"
}
]
}
] | [] | [] |
9257843 | 9257843 | [
{
"id": "9257843__text",
"type": "abstract",
"text": [
"Differential interaction of nuclear factors with the leukocyte-specific pp52 promoter in B and T cells. \nThe leukocyte-specific, cytoskeleton-binding pp52 (LSP-1, WP-34) protein is widely expressed in multiple leukocyte lineages, including B and T lymphocytes, granulocytes, and macrophages. We previously detected a tissue-specific promoter preceding the exon encoding the N terminus of the pp52 leukocyte protein. Here we describe the functional characterization of this promoter and identification of the factors in B and T cells that regulate its activity. The pp52 promoter contains an initiator specifying the unique 5' terminus of pp52 mRNA, tandem pairs of Ets and SP1 motifs, and a lone C/EBP motif. All these motifs are essential and collectively control transcriptional activity. DNA binding studies and Ab supershift assays revealed that different combinations of factors interact with these motifs in B cells vs T cells. The Ets motifs are preferentially bound by PU-1 in B cell extracts from all stages of development, whereas a different Ets family member reacts with these motifs in T cell extracts. The C/EBP motif is bound by Ig/EBP-1 in pre-B cell and T cell extracts, but is replaced by nuclear factor-IL-6beta or a nuclear factor-IL-6beta-Ig/EBP-1 heterodimer in plasmacytoma cell extracts. Despite its reported role as a negative regulator of transcription, Ig/EBP-1 appears to exert a stimulatory effect on this promoter. These findings reveal the features controlling the pp52 promoter in B and T cells and provide the foundation for determining the regulation of this promoter in other leukocyte lineages. "
],
"offsets": [
[
0,
1631
]
]
}
] | [
{
"id": "9257843_T1",
"type": "Protein",
"text": [
"pp52"
],
"offsets": [
[
72,
76
]
],
"normalized": []
},
{
"id": "9257843_T2",
"type": "Protein",
"text": [
"pp52"
],
"offsets": [
[
150,
154
]
],
"normalized": []
},
{
"id": "9257843_T3",
"type": "Protein",
"text": [
"LSP-1"
],
"offsets": [
[
156,
161
]
],
"normalized": []
},
{
"id": "9257843_T4",
"type": "Protein",
"text": [
"WP-34"
],
"offsets": [
[
163,
168
]
],
"normalized": []
},
{
"id": "9257843_T5",
"type": "Protein",
"text": [
"pp52 leukocyte protein"
],
"offsets": [
[
392,
414
]
],
"normalized": []
},
{
"id": "9257843_T6",
"type": "Protein",
"text": [
"pp52"
],
"offsets": [
[
565,
569
]
],
"normalized": []
},
{
"id": "9257843_T7",
"type": "Protein",
"text": [
"pp52"
],
"offsets": [
[
638,
642
]
],
"normalized": []
},
{
"id": "9257843_T8",
"type": "Protein",
"text": [
"PU-1"
],
"offsets": [
[
977,
981
]
],
"normalized": []
},
{
"id": "9257843_T9",
"type": "Protein",
"text": [
"Ig/EBP-1"
],
"offsets": [
[
1144,
1152
]
],
"normalized": []
},
{
"id": "9257843_T10",
"type": "Protein",
"text": [
"nuclear factor-IL-6beta"
],
"offsets": [
[
1207,
1230
]
],
"normalized": []
},
{
"id": "9257843_T11",
"type": "Protein",
"text": [
"nuclear factor-IL-6beta"
],
"offsets": [
[
1236,
1259
]
],
"normalized": []
},
{
"id": "9257843_T12",
"type": "Protein",
"text": [
"Ig/EBP-1"
],
"offsets": [
[
1260,
1268
]
],
"normalized": []
},
{
"id": "9257843_T13",
"type": "Protein",
"text": [
"Ig/EBP-1"
],
"offsets": [
[
1380,
1388
]
],
"normalized": []
},
{
"id": "9257843_T14",
"type": "Protein",
"text": [
"pp52"
],
"offsets": [
[
1496,
1500
]
],
"normalized": []
},
{
"id": "9257843_T16",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
570,
578
]
],
"normalized": []
},
{
"id": "9257843_T17",
"type": "Entity",
"text": [
"initiator"
],
"offsets": [
[
591,
600
]
],
"normalized": []
},
{
"id": "9257843_T19",
"type": "Entity",
"text": [
"5' terminus"
],
"offsets": [
[
623,
634
]
],
"normalized": []
},
{
"id": "9257843_T20",
"type": "Entity",
"text": [
"C/EBP motif"
],
"offsets": [
[
696,
707
]
],
"normalized": []
},
{
"id": "9257843_T27",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1501,
1509
]
],
"normalized": []
}
] | [
{
"id": "9257843_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
188,
197
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T3"
}
]
},
{
"id": "9257843_E2",
"type": "Regulation",
"trigger": {
"text": [
"specifying"
],
"offsets": [
[
601,
611
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T7"
},
{
"role": "Cause",
"ref_id": "9257843_T6"
},
{
"role": "Site",
"ref_id": "9257843_T19"
},
{
"role": "CSite",
"ref_id": "9257843_T17"
}
]
},
{
"id": "9257843_E3",
"type": "Binding",
"trigger": {
"text": [
"interact"
],
"offsets": [
[
884,
892
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T6"
},
{
"role": "Site",
"ref_id": "9257843_T20"
}
]
},
{
"id": "9257843_E4",
"type": "Binding",
"trigger": {
"text": [
"interact"
],
"offsets": [
[
884,
892
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T6"
},
{
"role": "Site",
"ref_id": "9257843_T17"
}
]
},
{
"id": "9257843_E5",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
968,
973
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T8"
}
]
},
{
"id": "9257843_E6",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
1135,
1140
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T9"
}
]
},
{
"id": "9257843_E7",
"type": "Binding",
"trigger": {
"text": [
"replaced"
],
"offsets": [
[
1195,
1203
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T10"
}
]
},
{
"id": "9257843_E8",
"type": "Binding",
"trigger": {
"text": [
"replaced"
],
"offsets": [
[
1195,
1203
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T11"
}
]
},
{
"id": "9257843_E9",
"type": "Binding",
"trigger": {
"text": [
"replaced"
],
"offsets": [
[
1195,
1203
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T12"
}
]
},
{
"id": "9257843_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"exert a stimulatory effect"
],
"offsets": [
[
1400,
1426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T6"
},
{
"role": "Cause",
"ref_id": "9257843_T13"
},
{
"role": "Site",
"ref_id": "9257843_T16"
}
]
},
{
"id": "9257843_E11",
"type": "Regulation",
"trigger": {
"text": [
"controlling"
],
"offsets": [
[
1480,
1491
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T14"
},
{
"role": "Site",
"ref_id": "9257843_T27"
}
]
},
{
"id": "9257843_E12",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1574,
1584
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9257843_T14"
},
{
"role": "Site",
"ref_id": "9257843_T27"
}
]
}
] | [
{
"id": "9257843_1",
"entity_ids": [
"9257843_T2",
"9257843_T3",
"9257843_T4"
]
}
] | [] |
7640302 | 7640302 | [
{
"id": "7640302__text",
"type": "abstract",
"text": [
"Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during erythroid differentiation [published erratum appears in Biochim Biophys Acta 1995 Dec 27;1264(3):409] \nHydroxyurea (HU) is an antitumor agent which also induces hemoglobinization during erythroid differentiation. In addition, HU stimulates the synthesis of fetal hemoglobin in sickle cell anemia patients. To further understand its mechanism of action, we investigated the effects of HU on regulation of c-jun expression prior to the onset of erythroid differentiation of K562 cells. HU induced a dose-dependent stimulation of c-jun synthesis. The levels of c-jun mRNA was elevated 4 to 7.5-fold by HU within 2 h. This was followed by a gradual decline to the basal level by 24 h. Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates c-jun mRNA expression by increasing the rate of synthesis as well as stabilizing the c-jun mRNA. In addition, the level of jun protein was elevated by 2 to 5-fold within 4 h in HU treated cells. Furthermore, concentrations of HU below 250 microM slightly increased the 5X AP-1/CAT activity. These results strongly suggest that HU induces both transcriptional and post-transcription regulation of c-jun during erythroid differentiation. "
],
"offsets": [
[
0,
1287
]
]
}
] | [
{
"id": "7640302_T1",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
14,
19
]
],
"normalized": []
},
{
"id": "7640302_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
482,
487
]
],
"normalized": []
},
{
"id": "7640302_T3",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
605,
610
]
],
"normalized": []
},
{
"id": "7640302_T4",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
636,
641
]
],
"normalized": []
},
{
"id": "7640302_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
851,
856
]
],
"normalized": []
},
{
"id": "7640302_T6",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
936,
941
]
],
"normalized": []
},
{
"id": "7640302_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1247,
1252
]
],
"normalized": []
}
] | [
{
"id": "7640302_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E2"
}
]
},
{
"id": "7640302_E2",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
25,
35
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T1"
}
]
},
{
"id": "7640302_E3",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
451,
458
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E4"
}
]
},
{
"id": "7640302_E4",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
468,
478
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E5"
}
]
},
{
"id": "7640302_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
488,
498
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T2"
}
]
},
{
"id": "7640302_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
565,
572
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E7"
}
]
},
{
"id": "7640302_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
590,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E8"
}
]
},
{
"id": "7640302_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
611,
620
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T3"
}
]
},
{
"id": "7640302_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"elevated"
],
"offsets": [
[
651,
659
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T4"
}
]
},
{
"id": "7640302_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"decline"
],
"offsets": [
[
723,
730
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E9"
}
]
},
{
"id": "7640302_E11",
"type": "Regulation",
"trigger": {
"text": [
"regulates"
],
"offsets": [
[
841,
850
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E12"
},
{
"role": "Cause",
"ref_id": "7640302_E13"
}
]
},
{
"id": "7640302_E12",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
862,
872
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T5"
}
]
},
{
"id": "7640302_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"increasing"
],
"offsets": [
[
876,
886
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E14"
}
]
},
{
"id": "7640302_E14",
"type": "Transcription",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
899,
908
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T6"
}
]
},
{
"id": "7640302_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"stabilizing"
],
"offsets": [
[
920,
931
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T6"
}
]
},
{
"id": "7640302_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1181,
1188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E21"
}
]
},
{
"id": "7640302_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1181,
1188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E20"
}
]
},
{
"id": "7640302_E18",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional"
],
"offsets": [
[
1194,
1209
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T7"
}
]
},
{
"id": "7640302_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"post-transcription"
],
"offsets": [
[
1214,
1232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_T7"
}
]
},
{
"id": "7640302_E20",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1233,
1243
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E19"
}
]
},
{
"id": "7640302_E21",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1233,
1243
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7640302_E18"
}
]
}
] | [] | [] |
10491412 | 10491412 | [
{
"id": "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": "10491412_T1",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
424,
436
]
],
"normalized": []
},
{
"id": "10491412_T2",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
601,
613
]
],
"normalized": []
},
{
"id": "10491412_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1144,
1148
]
],
"normalized": []
},
{
"id": "10491412_T4",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
1153,
1162
]
],
"normalized": []
}
] | [
{
"id": "10491412_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
378,
385
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_E2"
}
]
},
{
"id": "10491412_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
386,
397
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_T1"
}
]
},
{
"id": "10491412_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"normal level"
],
"offsets": [
[
568,
580
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_E5"
}
]
},
{
"id": "10491412_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
593,
600
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_E5"
}
]
},
{
"id": "10491412_E5",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
614,
625
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_T2"
}
]
},
{
"id": "10491412_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
1108,
1115
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_E8"
}
]
},
{
"id": "10491412_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
1108,
1115
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_E9"
}
]
},
{
"id": "10491412_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1116,
1126
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_T4"
}
]
},
{
"id": "10491412_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1116,
1126
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10491412_T3"
}
]
}
] | [] | [] |
9878608 | 9878608 | [
{
"id": "9878608__text",
"type": "abstract",
"text": [
"Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. \nKaposi's sarcoma (KS)-associated herpesvirus (KSHV), or human herpesvirus 8, is a lymphotropic virus strongly linked to several AIDS-related neoplasms. The primary reservoir of infection consists of latently infected B lymphocytes and possibly other mononuclear cells. Viral reactivation from latency and spread from this lymphoid reservoir is presumably required for development of nonlymphoid tumors like KS. Here we show that deregulated expression of a single viral gene, ORF 50, which encodes a transactivator able to selectively upregulate delayed-early viral genes, suffices to disrupt latency and induce the lytic gene cascade in latently infected B cells. The identification of this gene opens the way to studies of the physiologic mechanisms controlling reactvation of KSHV from latency. Copyright 1998 Academic Press. "
],
"offsets": [
[
0,
985
]
]
}
] | [
{
"id": "9878608_T1",
"type": "Protein",
"text": [
"ORF 50 transactivator"
],
"offsets": [
[
100,
121
]
],
"normalized": []
},
{
"id": "9878608_T2",
"type": "Protein",
"text": [
"EBV R"
],
"offsets": [
[
140,
145
]
],
"normalized": []
},
{
"id": "9878608_T3",
"type": "Protein",
"text": [
"ORF 50"
],
"offsets": [
[
632,
638
]
],
"normalized": []
}
] | [
{
"id": "9878608_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
82,
92
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9878608_T1"
}
]
},
{
"id": "9878608_E2",
"type": "Regulation",
"trigger": {
"text": [
"deregulated"
],
"offsets": [
[
585,
596
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9878608_E3"
}
]
},
{
"id": "9878608_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
597,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9878608_T3"
}
]
}
] | [] | [] |
8207643 | 8207643 | [
{
"id": "8207643__text",
"type": "abstract",
"text": [
"Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor. \nThis study examined the effects of leukemia inhibitory factor (LIF) on human immunodeficiency virus (HIV) replication in mononuclear phagocytes (MNP). LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1. The magnitude and time kinetics of the LIF effects were similar to interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF), other cytokines known to induce HIV replication in this cell line. To characterize mechanisms responsible for these LIF effects, levels of HIV mRNA, activation of the DNA binding protein nuclear factor (NF)-kB, signal transduction pathways, and potential interactions with other cytokines were analyzed. LIF increased steady-state levels of HIV mRNA at 2.0, 4.3, and 9.2 kB. This was detectable by 24 h and persisted until 72 h. The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription. NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937. In both cell lines LIF increased NF-kB activity. Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates. The oxygen radical scavenger N-acetyl-L-cysteine, but not an inhibitor of nitric oxide synthase, inhibited LIF-induced HIV replication. LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1, TNF, or IL-6. These results identify LIF as a stimulus of HIV replication. (ABSTRACT TRUNCATED AT 250 WORDS) "
],
"offsets": [
[
0,
1652
]
]
}
] | [
{
"id": "8207643_T1",
"type": "Protein",
"text": [
"leukemia inhibitory factor"
],
"offsets": [
[
60,
86
]
],
"normalized": []
},
{
"id": "8207643_T2",
"type": "Protein",
"text": [
"leukemia inhibitory factor"
],
"offsets": [
[
124,
150
]
],
"normalized": []
},
{
"id": "8207643_T3",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
152,
155
]
],
"normalized": []
},
{
"id": "8207643_T4",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
240,
243
]
],
"normalized": []
},
{
"id": "8207643_T5",
"type": "Protein",
"text": [
"p24 antigen"
],
"offsets": [
[
281,
292
]
],
"normalized": []
},
{
"id": "8207643_T6",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
398,
401
]
],
"normalized": []
},
{
"id": "8207643_T7",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
448,
452
]
],
"normalized": []
},
{
"id": "8207643_T8",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
603,
606
]
],
"normalized": []
},
{
"id": "8207643_T9",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
791,
794
]
],
"normalized": []
},
{
"id": "8207643_T10",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
1124,
1127
]
],
"normalized": []
},
{
"id": "8207643_T11",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
1378,
1381
]
],
"normalized": []
},
{
"id": "8207643_T12",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
1407,
1410
]
],
"normalized": []
},
{
"id": "8207643_T13",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1551,
1555
]
],
"normalized": []
},
{
"id": "8207643_T14",
"type": "Protein",
"text": [
"LIF"
],
"offsets": [
[
1580,
1583
]
],
"normalized": []
}
] | [
{
"id": "8207643_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
269,
277
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207643_E2"
},
{
"role": "Cause",
"ref_id": "8207643_T4"
}
]
},
{
"id": "8207643_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
293,
303
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207643_T5"
}
]
}
] | [
{
"id": "8207643_1",
"entity_ids": [
"8207643_T2",
"8207643_T3"
]
}
] | [] |
7543515 | 7543515 | [
{
"id": "7543515__text",
"type": "abstract",
"text": [
"Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors. \nWe have earlier shown that stimulation of human CD4+ T cells with SEA presented on Chinese hamster ovary (CHO)-DR transfectants coexpressing either B7 or LFA-3 resulted in distinct cytokine profiles. We now demonstrate that B7, but not LFA-3, strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells. Maximal increase in IL-2 transcription was recorded with CHO-DR/B7/LFA-3, suggesting a cooperative effect of B7 and LFA-3 at the transcriptional level. Gel-shift analysis demonstrated that stimulation of CD4+ T cells with CHO-DR and staphylococcal enterotoxin A was sufficient to induce significant amounts of NF-kappa B binding proteins, whereas induction of AP-1 binding proteins required costimulation. LFA-3 induced moderate levels of AP-1, but did not influence the levels of NF-kappa B, while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins. The CHO-DR/B7/LFA-3 triple transfectant induced a further increase in AP-1 and NF-kappa B binding proteins compared with the double transfectants. The level of Oct-1 binding proteins remained similar in all samples. Super-shift analysis revealed that the NF-kappa B complex of costimulated CD4+ T cells contained large amounts of p50, substantial amounts of p65, and marginal levels of c-Rel proteins. The AP-1 binding proteins contained c-Jun, Jun-D, and Fra-1, but marginal amounts of Jun-B and c-Fos. Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B. These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression. "
],
"offsets": [
[
0,
1761
]
]
}
] | [
{
"id": "7543515_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
23,
26
]
],
"normalized": []
},
{
"id": "7543515_T2",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
41,
46
]
],
"normalized": []
},
{
"id": "7543515_T3",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
51,
53
]
],
"normalized": []
},
{
"id": "7543515_T4",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
173,
176
]
],
"normalized": []
},
{
"id": "7543515_T5",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
273,
275
]
],
"normalized": []
},
{
"id": "7543515_T6",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
279,
284
]
],
"normalized": []
},
{
"id": "7543515_T7",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
349,
351
]
],
"normalized": []
},
{
"id": "7543515_T8",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
361,
366
]
],
"normalized": []
},
{
"id": "7543515_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
390,
394
]
],
"normalized": []
},
{
"id": "7543515_T10",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
432,
435
]
],
"normalized": []
},
{
"id": "7543515_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
466,
470
]
],
"normalized": []
},
{
"id": "7543515_T12",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
510,
512
]
],
"normalized": []
},
{
"id": "7543515_T13",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
513,
518
]
],
"normalized": []
},
{
"id": "7543515_T14",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
555,
557
]
],
"normalized": []
},
{
"id": "7543515_T15",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
562,
567
]
],
"normalized": []
},
{
"id": "7543515_T16",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
650,
653
]
],
"normalized": []
},
{
"id": "7543515_T17",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
852,
857
]
],
"normalized": []
},
{
"id": "7543515_T18",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
945,
947
]
],
"normalized": []
},
{
"id": "7543515_T19",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
1056,
1058
]
],
"normalized": []
},
{
"id": "7543515_T20",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
1059,
1064
]
],
"normalized": []
},
{
"id": "7543515_T21",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1335,
1338
]
],
"normalized": []
},
{
"id": "7543515_T22",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1375,
1378
]
],
"normalized": []
},
{
"id": "7543515_T23",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1403,
1406
]
],
"normalized": []
},
{
"id": "7543515_T24",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1431,
1436
]
],
"normalized": []
},
{
"id": "7543515_T25",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
1483,
1488
]
],
"normalized": []
},
{
"id": "7543515_T26",
"type": "Protein",
"text": [
"Jun-D"
],
"offsets": [
[
1490,
1495
]
],
"normalized": []
},
{
"id": "7543515_T27",
"type": "Protein",
"text": [
"Fra-1"
],
"offsets": [
[
1501,
1506
]
],
"normalized": []
},
{
"id": "7543515_T28",
"type": "Protein",
"text": [
"Jun-B"
],
"offsets": [
[
1532,
1537
]
],
"normalized": []
},
{
"id": "7543515_T29",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
1542,
1547
]
],
"normalized": []
},
{
"id": "7543515_T30",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
1590,
1592
]
],
"normalized": []
},
{
"id": "7543515_T31",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
1597,
1602
]
],
"normalized": []
},
{
"id": "7543515_T32",
"type": "Protein",
"text": [
"B7"
],
"offsets": [
[
1714,
1716
]
],
"normalized": []
},
{
"id": "7543515_T33",
"type": "Protein",
"text": [
"LFA-3"
],
"offsets": [
[
1721,
1726
]
],
"normalized": []
},
{
"id": "7543515_T34",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1744,
1748
]
],
"normalized": []
}
] | [
{
"id": "7543515_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpressing"
],
"offsets": [
[
253,
265
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_T6"
}
]
},
{
"id": "7543515_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpressing"
],
"offsets": [
[
253,
265
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_T5"
}
]
},
{
"id": "7543515_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"costimulated"
],
"offsets": [
[
377,
389
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E7"
},
{
"role": "Cause",
"ref_id": "7543515_T7"
}
]
},
{
"id": "7543515_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"costimulated"
],
"offsets": [
[
377,
389
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E8"
},
{
"role": "Cause",
"ref_id": "7543515_T7"
}
]
},
{
"id": "7543515_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"costimulated"
],
"offsets": [
[
377,
389
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E8"
},
{
"role": "Cause",
"ref_id": "7543515_T8"
}
]
},
{
"id": "7543515_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"costimulated"
],
"offsets": [
[
377,
389
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E7"
},
{
"role": "Cause",
"ref_id": "7543515_T8"
}
]
},
{
"id": "7543515_E7",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
395,
408
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_T9"
}
]
},
{
"id": "7543515_E8",
"type": "Transcription",
"trigger": {
"text": [
"mRNA expression"
],
"offsets": [
[
413,
428
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_T9"
}
]
},
{
"id": "7543515_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
454,
462
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E10"
}
]
},
{
"id": "7543515_E10",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
471,
484
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_T11"
}
]
},
{
"id": "7543515_E11",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
545,
551
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E10"
},
{
"role": "Cause",
"ref_id": "7543515_T14"
}
]
},
{
"id": "7543515_E12",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
545,
551
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E10"
},
{
"role": "Cause",
"ref_id": "7543515_T15"
}
]
},
{
"id": "7543515_E13",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
1703,
1710
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_E14"
}
]
},
{
"id": "7543515_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1749,
1759
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7543515_T34"
}
]
}
] | [] | [] |
9712047 | 9712047 | [
{
"id": "9712047__text",
"type": "abstract",
"text": [
"Cyclosporin A-resistant transactivation of the IL-2 promoter requires activity of okadaic acid-sensitive serine/threonine phosphatases. \nExpression of the IL-2 gene requires activation of T cells through stimulation of the TCR and costimulation through accessory receptors. We have found recently that okadaic acid-sensitive Ser/Thr phosphatases are involved in a cyclosporin A-insensitive pathway that selectively transmits costimulatory signals. In this study, we analyzed whether activities of these phosphatases are necessary for the expression of the IL-2 gene. In both activated peripheral blood T lymphocytes and activated tumorigenic T cell lines, IL-2 gene expression was blocked at the transcriptional level by okadaic acid. The transcription factors active at the IL-2 promoter were differentially influenced: upon down-modulation of okadaic acid-sensitive phosphatases, transactivation by octamer, NF-kappa B, and NF of activated T cells proteins was abrogated, while transactivation by AP-1 proteins was even enhanced. "
],
"offsets": [
[
0,
1032
]
]
}
] | [
{
"id": "9712047_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
47,
51
]
],
"normalized": []
},
{
"id": "9712047_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
155,
159
]
],
"normalized": []
},
{
"id": "9712047_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
556,
560
]
],
"normalized": []
},
{
"id": "9712047_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
656,
660
]
],
"normalized": []
},
{
"id": "9712047_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
775,
779
]
],
"normalized": []
},
{
"id": "9712047_T8",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
52,
60
]
],
"normalized": []
},
{
"id": "9712047_T17",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
780,
788
]
],
"normalized": []
}
] | [
{
"id": "9712047_E1",
"type": "Regulation",
"trigger": {
"text": [
"resistant"
],
"offsets": [
[
14,
23
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E2"
}
]
},
{
"id": "9712047_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
24,
39
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T1"
},
{
"role": "Site",
"ref_id": "9712047_T8"
}
]
},
{
"id": "9712047_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"requires"
],
"offsets": [
[
61,
69
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E2"
}
]
},
{
"id": "9712047_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"Expression"
],
"offsets": [
[
137,
147
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T2"
}
]
},
{
"id": "9712047_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"requires"
],
"offsets": [
[
165,
173
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E4"
}
]
},
{
"id": "9712047_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
"offsets": [
[
520,
529
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E7"
}
]
},
{
"id": "9712047_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
538,
548
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T3"
}
]
},
{
"id": "9712047_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocked"
],
"offsets": [
[
681,
688
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E9"
}
]
},
{
"id": "9712047_E9",
"type": "Transcription",
"trigger": {
"text": [
"at the transcriptional level"
],
"offsets": [
[
689,
717
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T4"
}
]
},
{
"id": "9712047_E10",
"type": "Binding",
"trigger": {
"text": [
"at"
],
"offsets": [
[
768,
770
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T5"
},
{
"role": "Site",
"ref_id": "9712047_T17"
}
]
},
{
"id": "9712047_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
882,
897
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T5"
},
{
"role": "Site",
"ref_id": "9712047_T17"
}
]
},
{
"id": "9712047_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"abrogated"
],
"offsets": [
[
963,
972
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E11"
}
]
},
{
"id": "9712047_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
980,
995
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_T5"
},
{
"role": "Site",
"ref_id": "9712047_T17"
}
]
},
{
"id": "9712047_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
1022,
1030
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9712047_E13"
}
]
}
] | [] | [] |
10069428 | 10069428 | [
{
"id": "10069428__text",
"type": "abstract",
"text": [
"Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients. \nAllergen-specific T cells in atopic patients are polarized IL-4-producing Th2 cells, promoting IgE synthesis by B cells. The molecular basis for increased IL-4 gene expression in atopy is not fully understood. IL-4 gene regulation in general involves the nuclear factor of activated T cells (NFAT) family of transcription factors, of which NFAT1 and NFAT2 are most prominent in peripheral T cells. Recently, a unique inhibitory role of NFAT1 in IL-4 gene control was shown in the mouse. In a series of electrophoretic mobility shift assays with protein extracts of highly polarized Th2 clones from atopics and Th1 clones from controls we compared DNA-binding activities at the two NFAT-binding elements P0 and P1 of the crucial proximal human IL-4 promoter. At the most proximal P0 site, NFAT-containing complexes devoid of NFAT2 were readily inducible in the Th1 clones, but hardly or not in the Th2 clones. In contrast, both in Th1 and Th2 clones NFAT-containing complexes were strongly inducible at the P1 site, consisting of NFAT2 and a P0-compatible NFAT activity, without apparent differences between Th1 and Th2 clones. Like in Th2 clones, suppressed NFAT-P0 complex formation was observed also at the polyclonal level in peripheral blood mononuclear cells (PBMC) of three of five severe atopic dermatitis patients with strongly elevated serum IgE levels, but not in control PBMC. These findings suggest that high-level IL-4 production in atopic Th2 cells is associated with selective reduction of suppressive NFAT1 activity at the IL-4 P0 element and that some patients with this multifactorial disease may have a putative systemic disorder at this level. "
],
"offsets": [
[
0,
1868
]
]
}
] | [
{
"id": "10069428_T1",
"type": "Protein",
"text": [
"NFAT1"
],
"offsets": [
[
61,
66
]
],
"normalized": []
},
{
"id": "10069428_T2",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
109,
113
]
],
"normalized": []
},
{
"id": "10069428_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
148,
152
]
],
"normalized": []
},
{
"id": "10069428_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
263,
267
]
],
"normalized": []
},
{
"id": "10069428_T5",
"type": "Protein",
"text": [
"IgE"
],
"offsets": [
[
299,
302
]
],
"normalized": []
},
{
"id": "10069428_T6",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
359,
363
]
],
"normalized": []
},
{
"id": "10069428_T7",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
414,
418
]
],
"normalized": []
},
{
"id": "10069428_T8",
"type": "Protein",
"text": [
"NFAT1"
],
"offsets": [
[
544,
549
]
],
"normalized": []
},
{
"id": "10069428_T9",
"type": "Protein",
"text": [
"NFAT2"
],
"offsets": [
[
554,
559
]
],
"normalized": []
},
{
"id": "10069428_T10",
"type": "Protein",
"text": [
"NFAT1"
],
"offsets": [
[
640,
645
]
],
"normalized": []
},
{
"id": "10069428_T11",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
649,
653
]
],
"normalized": []
},
{
"id": "10069428_T12",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
947,
951
]
],
"normalized": []
},
{
"id": "10069428_T13",
"type": "Protein",
"text": [
"NFAT2"
],
"offsets": [
[
1028,
1033
]
],
"normalized": []
},
{
"id": "10069428_T14",
"type": "Protein",
"text": [
"NFAT2"
],
"offsets": [
[
1233,
1238
]
],
"normalized": []
},
{
"id": "10069428_T15",
"type": "Protein",
"text": [
"IgE"
],
"offsets": [
[
1555,
1558
]
],
"normalized": []
},
{
"id": "10069428_T16",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1631,
1635
]
],
"normalized": []
},
{
"id": "10069428_T17",
"type": "Protein",
"text": [
"NFAT1"
],
"offsets": [
[
1721,
1726
]
],
"normalized": []
},
{
"id": "10069428_T18",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1743,
1747
]
],
"normalized": []
},
{
"id": "10069428_T20",
"type": "Entity",
"text": [
"proximal binding element P0"
],
"offsets": [
[
74,
101
]
],
"normalized": []
}
] | [
{
"id": "10069428_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"suppressed"
],
"offsets": [
[
13,
23
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T1"
},
{
"role": "Cause",
"ref_id": "10069428_E2"
}
]
},
{
"id": "10069428_E2",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
83,
90
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T1"
},
{
"role": "Theme",
"ref_id": "10069428_T2"
},
{
"role": "Site",
"ref_id": "10069428_T20"
}
]
},
{
"id": "10069428_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
139,
147
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E4"
}
]
},
{
"id": "10069428_E4",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
158,
171
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T3"
}
]
},
{
"id": "10069428_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"producing"
],
"offsets": [
[
268,
277
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T4"
}
]
},
{
"id": "10069428_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"promoting"
],
"offsets": [
[
289,
298
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E7"
},
{
"role": "Cause",
"ref_id": "10069428_E5"
}
]
},
{
"id": "10069428_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
303,
312
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T5"
}
]
},
{
"id": "10069428_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
349,
358
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E9"
}
]
},
{
"id": "10069428_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
369,
379
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T6"
}
]
},
{
"id": "10069428_E10",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
424,
434
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T7"
}
]
},
{
"id": "10069428_E11",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
446,
454
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E10"
},
{
"role": "Cause",
"ref_id": "10069428_T9"
}
]
},
{
"id": "10069428_E12",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
446,
454
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E10"
},
{
"role": "Cause",
"ref_id": "10069428_T8"
}
]
},
{
"id": "10069428_E13",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory role"
],
"offsets": [
[
621,
636
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E14"
},
{
"role": "Cause",
"ref_id": "10069428_T10"
}
]
},
{
"id": "10069428_E14",
"type": "Regulation",
"trigger": {
"text": [
"control"
],
"offsets": [
[
659,
666
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T11"
}
]
},
{
"id": "10069428_E15",
"type": "Binding",
"trigger": {
"text": [
"complexes"
],
"offsets": [
[
1008,
1017
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T13"
}
]
},
{
"id": "10069428_E16",
"type": "Binding",
"trigger": {
"text": [
"complexes"
],
"offsets": [
[
1169,
1178
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T14"
}
]
},
{
"id": "10069428_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducible"
],
"offsets": [
[
1193,
1202
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E16"
}
]
},
{
"id": "10069428_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"elevated"
],
"offsets": [
[
1540,
1548
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E19"
}
]
},
{
"id": "10069428_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
1559,
1565
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T15"
}
]
},
{
"id": "10069428_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"high-level"
],
"offsets": [
[
1620,
1630
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_E21"
}
]
},
{
"id": "10069428_E21",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1636,
1646
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10069428_T16"
}
]
}
] | [] | [] |
1448931 | 1448931 | [
{
"id": "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": "1448931_T1",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
385,
388
]
],
"normalized": []
},
{
"id": "1448931_T2",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
658,
661
]
],
"normalized": []
},
{
"id": "1448931_T3",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
776,
779
]
],
"normalized": []
},
{
"id": "1448931_T4",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1039,
1042
]
],
"normalized": []
},
{
"id": "1448931_T5",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1071,
1074
]
],
"normalized": []
}
] | [] | [] | [] |
9341193 | 9341193 | [
{
"id": "9341193__text",
"type": "abstract",
"text": [
"The tax protein of human T-cell leukemia virus type 1 mediates the transactivation of the c-sis/platelet-derived growth factor-B promoter through interactions with the zinc finger transcription factors Sp1 and NGFI-A/Egr-1. \nTranscriptional up-regulation of the c-sis/platelet-derived growth factor-B (PDGF-B) proto-oncogene by the Tax protein of human T-cell leukemia virus type 1 has been implicated as one possible mechanism of cellular transformation by human T-cell leukemia virus type 1. In previous work, we identified an essential site in the c-sis/PDGF-B promoter, Tax-responsive element 1 (TRE1), necessary for transactivation by Tax. We also identified Sp1, Sp3, and NGFI-A/Egr-1 as the primary nuclear transcription factors binding to TRE1 which mediate Tax responsiveness. In the present work, we have investigated the mechanism(s) whereby Tax transactivates the c-sis/PDGF-B proto-oncogene. In vitro transcription assays showed that Tax was able to significantly increase the transcriptional activity of a template containing the -257 to +74 region of the c-sis/PDGF-B promoter. Electrophoretic mobility shift assay analysis showed that Tax increased the DNA binding activity of both Sp1 and NGFI-A/Egr-1 using a TRE1 probe. Analysis of Tax mutants showed that two mutants, IEXC29S and IEXL320G, were unable to significantly transactivate the c-sis/PDGF-B promoter. Finally, co-immunoprecipitation analysis revealed that Tax is able to stably bind to both Sp1 and NGFI-A/Egr-1. Interestingly, co-immunoprecipitation analysis also revealed that Tax mutant IEXC29S is unable to interact with NGFI-A/Egr-1, whereas Tax mutant IEXL320G is able to interact with NGFI-A/Egr-1. "
],
"offsets": [
[
0,
1685
]
]
}
] | [
{
"id": "9341193_T1",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
4,
7
]
],
"normalized": []
},
{
"id": "9341193_T2",
"type": "Protein",
"text": [
"c-sis"
],
"offsets": [
[
90,
95
]
],
"normalized": []
},
{
"id": "9341193_T3",
"type": "Protein",
"text": [
"platelet-derived growth factor-B"
],
"offsets": [
[
96,
128
]
],
"normalized": []
},
{
"id": "9341193_T4",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
202,
205
]
],
"normalized": []
},
{
"id": "9341193_T5",
"type": "Protein",
"text": [
"NGFI-A"
],
"offsets": [
[
210,
216
]
],
"normalized": []
},
{
"id": "9341193_T6",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
217,
222
]
],
"normalized": []
},
{
"id": "9341193_T7",
"type": "Protein",
"text": [
"c-sis"
],
"offsets": [
[
262,
267
]
],
"normalized": []
},
{
"id": "9341193_T8",
"type": "Protein",
"text": [
"platelet-derived growth factor-B"
],
"offsets": [
[
268,
300
]
],
"normalized": []
},
{
"id": "9341193_T9",
"type": "Protein",
"text": [
"PDGF-B"
],
"offsets": [
[
302,
308
]
],
"normalized": []
},
{
"id": "9341193_T10",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
332,
335
]
],
"normalized": []
},
{
"id": "9341193_T11",
"type": "Protein",
"text": [
"c-sis"
],
"offsets": [
[
551,
556
]
],
"normalized": []
},
{
"id": "9341193_T12",
"type": "Protein",
"text": [
"PDGF-B"
],
"offsets": [
[
557,
563
]
],
"normalized": []
},
{
"id": "9341193_T13",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
574,
577
]
],
"normalized": []
},
{
"id": "9341193_T14",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
640,
643
]
],
"normalized": []
},
{
"id": "9341193_T15",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
664,
667
]
],
"normalized": []
},
{
"id": "9341193_T16",
"type": "Protein",
"text": [
"Sp3"
],
"offsets": [
[
669,
672
]
],
"normalized": []
},
{
"id": "9341193_T17",
"type": "Protein",
"text": [
"NGFI-A"
],
"offsets": [
[
678,
684
]
],
"normalized": []
},
{
"id": "9341193_T18",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
685,
690
]
],
"normalized": []
},
{
"id": "9341193_T19",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
766,
769
]
],
"normalized": []
},
{
"id": "9341193_T20",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
853,
856
]
],
"normalized": []
},
{
"id": "9341193_T21",
"type": "Protein",
"text": [
"c-sis"
],
"offsets": [
[
876,
881
]
],
"normalized": []
},
{
"id": "9341193_T22",
"type": "Protein",
"text": [
"PDGF-B"
],
"offsets": [
[
882,
888
]
],
"normalized": []
},
{
"id": "9341193_T23",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
947,
950
]
],
"normalized": []
},
{
"id": "9341193_T24",
"type": "Protein",
"text": [
"c-sis"
],
"offsets": [
[
1070,
1075
]
],
"normalized": []
},
{
"id": "9341193_T25",
"type": "Protein",
"text": [
"PDGF-B"
],
"offsets": [
[
1076,
1082
]
],
"normalized": []
},
{
"id": "9341193_T26",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1151,
1154
]
],
"normalized": []
},
{
"id": "9341193_T27",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1198,
1201
]
],
"normalized": []
},
{
"id": "9341193_T28",
"type": "Protein",
"text": [
"NGFI-A"
],
"offsets": [
[
1206,
1212
]
],
"normalized": []
},
{
"id": "9341193_T29",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
1213,
1218
]
],
"normalized": []
},
{
"id": "9341193_T30",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1251,
1254
]
],
"normalized": []
},
{
"id": "9341193_T31",
"type": "Protein",
"text": [
"c-sis"
],
"offsets": [
[
1357,
1362
]
],
"normalized": []
},
{
"id": "9341193_T32",
"type": "Protein",
"text": [
"PDGF-B"
],
"offsets": [
[
1363,
1369
]
],
"normalized": []
},
{
"id": "9341193_T33",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1435,
1438
]
],
"normalized": []
},
{
"id": "9341193_T34",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1470,
1473
]
],
"normalized": []
},
{
"id": "9341193_T35",
"type": "Protein",
"text": [
"NGFI-A"
],
"offsets": [
[
1478,
1484
]
],
"normalized": []
},
{
"id": "9341193_T36",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
1485,
1490
]
],
"normalized": []
},
{
"id": "9341193_T37",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1558,
1561
]
],
"normalized": []
},
{
"id": "9341193_T38",
"type": "Protein",
"text": [
"NGFI-A"
],
"offsets": [
[
1604,
1610
]
],
"normalized": []
},
{
"id": "9341193_T39",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
1611,
1616
]
],
"normalized": []
},
{
"id": "9341193_T40",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1626,
1629
]
],
"normalized": []
},
{
"id": "9341193_T41",
"type": "Protein",
"text": [
"NGFI-A"
],
"offsets": [
[
1671,
1677
]
],
"normalized": []
},
{
"id": "9341193_T42",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
1678,
1683
]
],
"normalized": []
},
{
"id": "9341193_T44",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
129,
137
]
],
"normalized": []
},
{
"id": "9341193_T54",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1370,
1378
]
],
"normalized": []
}
] | [
{
"id": "9341193_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
67,
82
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T2"
},
{
"role": "Cause",
"ref_id": "9341193_E4"
},
{
"role": "Site",
"ref_id": "9341193_T44"
}
]
},
{
"id": "9341193_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
67,
82
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T2"
},
{
"role": "Cause",
"ref_id": "9341193_E3"
},
{
"role": "Site",
"ref_id": "9341193_T44"
}
]
},
{
"id": "9341193_E3",
"type": "Binding",
"trigger": {
"text": [
"interactions"
],
"offsets": [
[
146,
158
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T1"
},
{
"role": "Theme",
"ref_id": "9341193_T4"
}
]
},
{
"id": "9341193_E4",
"type": "Binding",
"trigger": {
"text": [
"interactions"
],
"offsets": [
[
146,
158
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T1"
},
{
"role": "Theme",
"ref_id": "9341193_T5"
}
]
},
{
"id": "9341193_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"Transcriptional up-regulation"
],
"offsets": [
[
225,
254
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T7"
},
{
"role": "Cause",
"ref_id": "9341193_T10"
}
]
},
{
"id": "9341193_E6",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
736,
743
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T15"
}
]
},
{
"id": "9341193_E7",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
736,
743
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T16"
}
]
},
{
"id": "9341193_E8",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
736,
743
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T17"
}
]
},
{
"id": "9341193_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivates"
],
"offsets": [
[
857,
871
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T21"
},
{
"role": "Cause",
"ref_id": "9341193_T20"
}
]
},
{
"id": "9341193_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
977,
985
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_E11"
},
{
"role": "Cause",
"ref_id": "9341193_T23"
}
]
},
{
"id": "9341193_E11",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional activity"
],
"offsets": [
[
990,
1014
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T24"
}
]
},
{
"id": "9341193_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1155,
1164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_E15"
},
{
"role": "Cause",
"ref_id": "9341193_T26"
}
]
},
{
"id": "9341193_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1155,
1164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_E14"
},
{
"role": "Cause",
"ref_id": "9341193_T26"
}
]
},
{
"id": "9341193_E14",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
1173,
1189
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T28"
}
]
},
{
"id": "9341193_E15",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
1173,
1189
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T27"
}
]
},
{
"id": "9341193_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivate"
],
"offsets": [
[
1339,
1352
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T31"
},
{
"role": "Site",
"ref_id": "9341193_T54"
}
]
},
{
"id": "9341193_E17",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
1457,
1461
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T33"
},
{
"role": "Theme",
"ref_id": "9341193_T34"
}
]
},
{
"id": "9341193_E18",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
1457,
1461
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T33"
},
{
"role": "Theme",
"ref_id": "9341193_T35"
}
]
},
{
"id": "9341193_E19",
"type": "Binding",
"trigger": {
"text": [
"interact"
],
"offsets": [
[
1590,
1598
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T38"
}
]
},
{
"id": "9341193_E20",
"type": "Binding",
"trigger": {
"text": [
"interact"
],
"offsets": [
[
1657,
1665
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9341193_T42"
}
]
}
] | [
{
"id": "9341193_1",
"entity_ids": [
"9341193_T28",
"9341193_T29"
]
},
{
"id": "9341193_2",
"entity_ids": [
"9341193_T11",
"9341193_T12"
]
},
{
"id": "9341193_3",
"entity_ids": [
"9341193_T35",
"9341193_T36"
]
},
{
"id": "9341193_4",
"entity_ids": [
"9341193_T2",
"9341193_T3"
]
},
{
"id": "9341193_5",
"entity_ids": [
"9341193_T17",
"9341193_T18"
]
},
{
"id": "9341193_6",
"entity_ids": [
"9341193_T38",
"9341193_T39"
]
},
{
"id": "9341193_7",
"entity_ids": [
"9341193_T24",
"9341193_T25"
]
},
{
"id": "9341193_8",
"entity_ids": [
"9341193_T31",
"9341193_T32"
]
},
{
"id": "9341193_9",
"entity_ids": [
"9341193_T21",
"9341193_T22"
]
},
{
"id": "9341193_10",
"entity_ids": [
"9341193_T5",
"9341193_T6"
]
},
{
"id": "9341193_11",
"entity_ids": [
"9341193_T41",
"9341193_T42"
]
},
{
"id": "9341193_12",
"entity_ids": [
"9341193_T7",
"9341193_T8",
"9341193_T9"
]
}
] | [] |
8506326 | 8506326 | [
{
"id": "8506326__text",
"type": "abstract",
"text": [
"Molecular basis of a multiple lymphokine deficiency in a patient with severe combined immunodeficiency. \nWe have previously reported that the T lymphocytes of a child with severe combined immunodeficiency are defective in the transcription of several lymphokine genes that include IL2, IL3, IL4, and IL5, which encode interleukins 2, 3, 4, and 5 (IL-2, -3, -4, and -5). To determine whether the defect in the patient's T lymphocytes involved a trans-acting factor common to the affected lymphokine genes, we examined the ability of nuclear factors from the patient's T lymphocytes to bind response elements present in the regulatory region of IL2. Nuclear factor NF-kB, activation protein 1 (AP-1), OCT-1, and NF-IL-2B binding activity were normal. In contrast, the binding of the nuclear factor of activated T cells (NF-AT) to its response element in the IL2 enhancer and to an NF-AT-like response element present in the IL4 enhancer was abnormal. To ascertain whether the abnormal NF-AT binding activity was related to an impaired function, we transfected patient and control T lymphocytes with constructs containing the reporter gene encoding chloramphenicol acetyl transferase (CAT) under the control of the entire IL2 regulatory region or of multimers of individual enhancer sequences. CAT expression directed by the IL2 regulatory region or by a multimer of the NF-AT-binding site was markedly lower in the patient relative to controls. In contrast, CAT gene expression directed by a multimer of the OCT-1 proximal (OCT-1p)-binding site was equivalent in patient and controls. These results indicate that an abnormality of/or influencing NF-AT may underlie the multiple lymphokine deficiency in this patient. "
],
"offsets": [
[
0,
1715
]
]
}
] | [
{
"id": "8506326_T1",
"type": "Protein",
"text": [
"IL2"
],
"offsets": [
[
281,
284
]
],
"normalized": []
},
{
"id": "8506326_T2",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
286,
289
]
],
"normalized": []
},
{
"id": "8506326_T3",
"type": "Protein",
"text": [
"IL4"
],
"offsets": [
[
291,
294
]
],
"normalized": []
},
{
"id": "8506326_T4",
"type": "Protein",
"text": [
"IL5"
],
"offsets": [
[
300,
303
]
],
"normalized": []
},
{
"id": "8506326_T5",
"type": "Protein",
"text": [
"interleukins 2"
],
"offsets": [
[
318,
332
]
],
"normalized": []
},
{
"id": "8506326_T6",
"type": "Protein",
"text": [
"3"
],
"offsets": [
[
334,
335
]
],
"normalized": []
},
{
"id": "8506326_T7",
"type": "Protein",
"text": [
"4"
],
"offsets": [
[
337,
338
]
],
"normalized": []
},
{
"id": "8506326_T8",
"type": "Protein",
"text": [
"5"
],
"offsets": [
[
344,
345
]
],
"normalized": []
},
{
"id": "8506326_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
347,
351
]
],
"normalized": []
},
{
"id": "8506326_T10",
"type": "Protein",
"text": [
"-3"
],
"offsets": [
[
353,
355
]
],
"normalized": []
},
{
"id": "8506326_T11",
"type": "Protein",
"text": [
"-4"
],
"offsets": [
[
357,
359
]
],
"normalized": []
},
{
"id": "8506326_T12",
"type": "Protein",
"text": [
"-5"
],
"offsets": [
[
365,
367
]
],
"normalized": []
},
{
"id": "8506326_T13",
"type": "Protein",
"text": [
"IL2"
],
"offsets": [
[
643,
646
]
],
"normalized": []
},
{
"id": "8506326_T14",
"type": "Protein",
"text": [
"OCT-1"
],
"offsets": [
[
699,
704
]
],
"normalized": []
},
{
"id": "8506326_T15",
"type": "Protein",
"text": [
"IL2"
],
"offsets": [
[
856,
859
]
],
"normalized": []
},
{
"id": "8506326_T16",
"type": "Protein",
"text": [
"IL4"
],
"offsets": [
[
922,
925
]
],
"normalized": []
},
{
"id": "8506326_T17",
"type": "Protein",
"text": [
"chloramphenicol acetyl transferase"
],
"offsets": [
[
1146,
1180
]
],
"normalized": []
},
{
"id": "8506326_T18",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1182,
1185
]
],
"normalized": []
},
{
"id": "8506326_T19",
"type": "Protein",
"text": [
"IL2"
],
"offsets": [
[
1219,
1222
]
],
"normalized": []
},
{
"id": "8506326_T20",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1291,
1294
]
],
"normalized": []
},
{
"id": "8506326_T21",
"type": "Protein",
"text": [
"IL2"
],
"offsets": [
[
1322,
1325
]
],
"normalized": []
},
{
"id": "8506326_T22",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1456,
1459
]
],
"normalized": []
},
{
"id": "8506326_T23",
"type": "Protein",
"text": [
"OCT-1"
],
"offsets": [
[
1506,
1511
]
],
"normalized": []
},
{
"id": "8506326_T27",
"type": "Entity",
"text": [
"response elements"
],
"offsets": [
[
589,
606
]
],
"normalized": []
},
{
"id": "8506326_T30",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
860,
868
]
],
"normalized": []
},
{
"id": "8506326_T31",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
926,
934
]
],
"normalized": []
}
] | [
{
"id": "8506326_E1",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
226,
239
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T1"
}
]
},
{
"id": "8506326_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
226,
239
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T3"
}
]
},
{
"id": "8506326_E3",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
226,
239
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T4"
}
]
},
{
"id": "8506326_E4",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
226,
239
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T2"
}
]
},
{
"id": "8506326_E5",
"type": "Regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
433,
441
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_E4"
}
]
},
{
"id": "8506326_E6",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
584,
588
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T13"
},
{
"role": "Site",
"ref_id": "8506326_T27"
}
]
},
{
"id": "8506326_E7",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
719,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T13"
},
{
"role": "Site",
"ref_id": "8506326_T27"
}
]
},
{
"id": "8506326_E8",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
719,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T14"
},
{
"role": "Theme",
"ref_id": "8506326_T13"
},
{
"role": "Site",
"ref_id": "8506326_T27"
}
]
},
{
"id": "8506326_E9",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
766,
773
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T15"
},
{
"role": "Site",
"ref_id": "8506326_T30"
}
]
},
{
"id": "8506326_E10",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
766,
773
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T16"
},
{
"role": "Site",
"ref_id": "8506326_T31"
}
]
},
{
"id": "8506326_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"transfected"
],
"offsets": [
[
1046,
1057
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T18"
}
]
},
{
"id": "8506326_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"transfected"
],
"offsets": [
[
1046,
1057
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_E11"
}
]
},
{
"id": "8506326_E13",
"type": "Regulation",
"trigger": {
"text": [
"under the control"
],
"offsets": [
[
1187,
1204
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T18"
}
]
},
{
"id": "8506326_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1295,
1305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T20"
}
]
},
{
"id": "8506326_E15",
"type": "Regulation",
"trigger": {
"text": [
"directed"
],
"offsets": [
[
1306,
1314
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_E14"
}
]
},
{
"id": "8506326_E16",
"type": "Negative_regulation",
"trigger": {
"text": [
"lower"
],
"offsets": [
[
1400,
1405
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_E14"
}
]
},
{
"id": "8506326_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1465,
1475
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_T22"
}
]
},
{
"id": "8506326_E18",
"type": "Negative_regulation",
"trigger": {
"text": [
"equivalent"
],
"offsets": [
[
1547,
1557
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8506326_E17"
}
]
}
] | [
{
"id": "8506326_1",
"entity_ids": [
"8506326_T17",
"8506326_T18"
]
}
] | [] |
1431113 | 1431113 | [
{
"id": "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": "1431113_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
954,
957
]
],
"normalized": []
}
] | [
{
"id": "1431113_E1",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
969,
985
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1431113_T1"
}
]
}
] | [] | [] |
8797708 | 8797708 | [
{
"id": "8797708__text",
"type": "abstract",
"text": [
"Interaction of HTLV-I Tax with the human proteasome: implications for NF-kappa B induction. \nThe human T-cell leukemia virus type I (HTLV-I) has been etiologically associated with the development of the adult T-cell leukemia (ATL) as well as degenerative neurologic syndrome termed tropical spastic paraparesis (TSP). HTLV-I encodes a potent transactivator protein termed Tax that appears to play an important role in the process of T-cell immortalization. Even though the mechanisms by which Tax induces transformation are still unknown, it seems likely that the ability of Tax to alter the expression of many cellular genes plays an important part in this process. Tax does not bind directly to DNA but rather deregulates the activity of cellular transcription factors. One family of host transcription factors whose activity is altered by Tax includes NF-kappa B/Rel. These transcription factors are post-transcriptionally regulated by their assembly with a second family of inhibitory proteins termed I kappa B that serve to sequester the NF-kappa B/Rel complexes in the cytoplasm. Upon cellular activation, I kappa B alpha is phosphorylated, polyubiquitinated, and degraded in the proteasome. This proteolytic event liberates NF-kappa B, permitting its rapid translocation into the nucleus where it binds to its cognate enhancer elements. Similarly, the p105 precursor of the NF-kappa B p50 subunit is also post-translationally processed in the proteasome. The mechanisms by which Tax activates NF-kappa B remain unclear, and findings presented in the literature are often controversial. We identified a physical interaction between Tax and the HsN3 subunit of the human proteasome. This raises the intriguing possibility that physical association of the HsN3 proteasome subunit with HTLV-I Tax coupled with the independent interaction of Tax with either p100 or p65-I kappa B alpha targets these cytoplasmic NF-kappa B/Rel complexes to the proteasome for processing. "
],
"offsets": [
[
0,
1973
]
]
}
] | [
{
"id": "8797708_T1",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
22,
25
]
],
"normalized": []
},
{
"id": "8797708_T2",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "8797708_T3",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
493,
496
]
],
"normalized": []
},
{
"id": "8797708_T4",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
575,
578
]
],
"normalized": []
},
{
"id": "8797708_T5",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
667,
670
]
],
"normalized": []
},
{
"id": "8797708_T6",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
842,
845
]
],
"normalized": []
},
{
"id": "8797708_T7",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1112,
1127
]
],
"normalized": []
},
{
"id": "8797708_T8",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1359,
1363
]
],
"normalized": []
},
{
"id": "8797708_T9",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1392,
1395
]
],
"normalized": []
},
{
"id": "8797708_T10",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1486,
1489
]
],
"normalized": []
},
{
"id": "8797708_T11",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1638,
1641
]
],
"normalized": []
},
{
"id": "8797708_T12",
"type": "Protein",
"text": [
"HsN3"
],
"offsets": [
[
1650,
1654
]
],
"normalized": []
},
{
"id": "8797708_T13",
"type": "Protein",
"text": [
"HsN3"
],
"offsets": [
[
1760,
1764
]
],
"normalized": []
},
{
"id": "8797708_T14",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1796,
1799
]
],
"normalized": []
},
{
"id": "8797708_T15",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1844,
1847
]
],
"normalized": []
},
{
"id": "8797708_T16",
"type": "Protein",
"text": [
"p100"
],
"offsets": [
[
1860,
1864
]
],
"normalized": []
},
{
"id": "8797708_T17",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1868,
1871
]
],
"normalized": []
},
{
"id": "8797708_T18",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1872,
1887
]
],
"normalized": []
}
] | [
{
"id": "8797708_E1",
"type": "Binding",
"trigger": {
"text": [
"Interaction"
],
"offsets": [
[
0,
11
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T1"
}
]
},
{
"id": "8797708_E2",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
680,
684
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T5"
}
]
},
{
"id": "8797708_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"Upon"
],
"offsets": [
[
1086,
1090
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_E6"
}
]
},
{
"id": "8797708_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"Upon"
],
"offsets": [
[
1086,
1090
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_E5"
}
]
},
{
"id": "8797708_E5",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
1131,
1145
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T7"
}
]
},
{
"id": "8797708_E6",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
1170,
1178
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T7"
}
]
},
{
"id": "8797708_E7",
"type": "Binding",
"trigger": {
"text": [
"physical interaction"
],
"offsets": [
[
1609,
1629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T11"
},
{
"role": "Theme",
"ref_id": "8797708_T12"
}
]
},
{
"id": "8797708_E8",
"type": "Binding",
"trigger": {
"text": [
"physical association"
],
"offsets": [
[
1732,
1752
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T13"
},
{
"role": "Theme",
"ref_id": "8797708_T14"
}
]
},
{
"id": "8797708_E9",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1829,
1840
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T15"
},
{
"role": "Theme",
"ref_id": "8797708_T18"
},
{
"role": "Theme",
"ref_id": "8797708_T16"
}
]
},
{
"id": "8797708_E10",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1829,
1840
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8797708_T15"
},
{
"role": "Theme",
"ref_id": "8797708_T18"
},
{
"role": "Theme",
"ref_id": "8797708_T17"
}
]
}
] | [] | [] |
1851861 | 1851861 | [
{
"id": "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
]
]
}
] | [] | [] | [] | [] |
10202027 | 10202027 | [
{
"id": "10202027__text",
"type": "abstract",
"text": [
"Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae. \nChlamydia pneumoniae is an important respiratory pathogen. Recently, its presence has been demonstrated in atherosclerotic lesions. In this study, we characterized C. pneumoniae-mediated activation of endothelial cells and demonstrated an enhanced expression of endothelial adhesion molecules followed by subsequent rolling, adhesion, and transmigration of leukocytes (monocytes, granulocytes). These effects were blocked by mAbs against endothelial and/or leukocyte adhesion molecules (beta1 and beta2 integrins). Additionally, activation of different signal transduction pathways in C. pneumoniae-infected endothelial cells was shown: protein tyrosine phosphorylation, up-regulation of phosphorylated p42/p44 mitogen-activated protein kinase, and NF-kappaB activation/translocation occurred within 10-15 min. Increased mRNA and surface expression of E-selectin, ICAM-1, and VCAM-1 were noted within hours. Thus, C. pneumoniae triggers a cascade of events that could lead to endothelial activation, inflammation, and thrombosis, which in turn may result in or may promote atherosclerosis. "
],
"offsets": [
[
0,
1198
]
]
}
] | [
{
"id": "10202027_T1",
"type": "Protein",
"text": [
"beta1"
],
"offsets": [
[
595,
600
]
],
"normalized": []
},
{
"id": "10202027_T2",
"type": "Protein",
"text": [
"beta2 integrins"
],
"offsets": [
[
605,
620
]
],
"normalized": []
},
{
"id": "10202027_T3",
"type": "Protein",
"text": [
"p42"
],
"offsets": [
[
811,
814
]
],
"normalized": []
},
{
"id": "10202027_T4",
"type": "Protein",
"text": [
"p44 mitogen-activated protein kinase"
],
"offsets": [
[
815,
851
]
],
"normalized": []
},
{
"id": "10202027_T5",
"type": "Protein",
"text": [
"E-selectin"
],
"offsets": [
[
960,
970
]
],
"normalized": []
},
{
"id": "10202027_T6",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
972,
978
]
],
"normalized": []
},
{
"id": "10202027_T7",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
984,
990
]
],
"normalized": []
}
] | [
{
"id": "10202027_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
779,
792
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T3"
}
]
},
{
"id": "10202027_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
779,
792
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T4"
}
]
},
{
"id": "10202027_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"occurred"
],
"offsets": [
[
892,
900
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E1"
}
]
},
{
"id": "10202027_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increased"
],
"offsets": [
[
919,
928
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E10"
}
]
},
{
"id": "10202027_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increased"
],
"offsets": [
[
919,
928
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E12"
}
]
},
{
"id": "10202027_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increased"
],
"offsets": [
[
919,
928
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E14"
}
]
},
{
"id": "10202027_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increased"
],
"offsets": [
[
919,
928
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E13"
}
]
},
{
"id": "10202027_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increased"
],
"offsets": [
[
919,
928
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E15"
}
]
},
{
"id": "10202027_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increased"
],
"offsets": [
[
919,
928
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_E11"
}
]
},
{
"id": "10202027_E10",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
946,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T6"
}
]
},
{
"id": "10202027_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
946,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T6"
}
]
},
{
"id": "10202027_E12",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
946,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T7"
}
]
},
{
"id": "10202027_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
946,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T7"
}
]
},
{
"id": "10202027_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
946,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T5"
}
]
},
{
"id": "10202027_E15",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
946,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202027_T5"
}
]
}
] | [] | [] |
10377075 | 10377075 | [
{
"id": "10377075__text",
"type": "abstract",
"text": [
"PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. \nBACKGROUND: Adhesion molecule expression on the endothelial cell (EC) surface is critical for leukocyte recruitment to atherosclerotic lesions. Better understanding of transcriptional regulation of adhesion molecules in ECs may provide important insight into plaque formation. Peroxisome proliferator-activated receptor-alpha (PPARalpha), a member of the nuclear receptor family, regulates gene expression in response to certain fatty acids and fibric acid derivatives. The present study investigated PPARalpha expression in human ECs and their regulation of vascular cell adhesion molecule-1 (VCAM-1). METHODS AND RESULTS: Immunohistochemistry revealed that human carotid artery ECs express PPARalpha. Pretreatment of cultured human ECs with the PPARalpha activators fenofibrate or WY14643 inhibited TNF-alpha-induced VCAM-1 in a time- and concentration-dependent manner, an effect not seen with PPARgamma activators. Both PPARalpha activators decreased cytokine-induced VCAM-1 mRNA expression without altering its mRNA half-life. Transient transfection of deletional VCAM-1 promoter constructs and electrophoretic mobility shift assays suggest that fenofibrate inhibits VCAM-1 transcription in part by inhibiting NF-kappaB. Finally, PPARalpha activators significantly reduced adhesion of U937 cells to cultured human ECs. CONCLUSIONS: Human ECs express PPARalpha, a potentially important regulator of atherogenesis through its transcriptional control of VCAM-1 gene expression. Such findings also have implications regarding the clinical use of lipid-lowering agents, like fibric acids, which can activate PPARalpha. "
],
"offsets": [
[
0,
1739
]
]
}
] | [
{
"id": "10377075_T1",
"type": "Protein",
"text": [
"vascular cell adhesion molecule-1"
],
"offsets": [
[
46,
79
]
],
"normalized": []
},
{
"id": "10377075_T2",
"type": "Protein",
"text": [
"Peroxisome proliferator-activated receptor-alpha"
],
"offsets": [
[
397,
445
]
],
"normalized": []
},
{
"id": "10377075_T3",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
447,
456
]
],
"normalized": []
},
{
"id": "10377075_T4",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
621,
630
]
],
"normalized": []
},
{
"id": "10377075_T5",
"type": "Protein",
"text": [
"vascular cell adhesion molecule-1"
],
"offsets": [
[
679,
712
]
],
"normalized": []
},
{
"id": "10377075_T6",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
714,
720
]
],
"normalized": []
},
{
"id": "10377075_T7",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
812,
821
]
],
"normalized": []
},
{
"id": "10377075_T8",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
867,
876
]
],
"normalized": []
},
{
"id": "10377075_T9",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
921,
930
]
],
"normalized": []
},
{
"id": "10377075_T10",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
939,
945
]
],
"normalized": []
},
{
"id": "10377075_T11",
"type": "Protein",
"text": [
"PPARgamma"
],
"offsets": [
[
1017,
1026
]
],
"normalized": []
},
{
"id": "10377075_T12",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
1044,
1053
]
],
"normalized": []
},
{
"id": "10377075_T13",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
1092,
1098
]
],
"normalized": []
},
{
"id": "10377075_T14",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
1189,
1195
]
],
"normalized": []
},
{
"id": "10377075_T15",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
1292,
1298
]
],
"normalized": []
},
{
"id": "10377075_T16",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
1355,
1364
]
],
"normalized": []
},
{
"id": "10377075_T17",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
1475,
1484
]
],
"normalized": []
},
{
"id": "10377075_T18",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
1576,
1582
]
],
"normalized": []
},
{
"id": "10377075_T19",
"type": "Protein",
"text": [
"PPARalpha"
],
"offsets": [
[
1728,
1737
]
],
"normalized": []
}
] | [
{
"id": "10377075_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
21,
28
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_E2"
}
]
},
{
"id": "10377075_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
38,
45
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_E3"
}
]
},
{
"id": "10377075_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
80,
90
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T1"
}
]
},
{
"id": "10377075_E4",
"type": "Regulation",
"trigger": {
"text": [
"in response to"
],
"offsets": [
[
526,
540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T3"
}
]
},
{
"id": "10377075_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
631,
641
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T4"
}
]
},
{
"id": "10377075_E6",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
665,
675
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T6"
},
{
"role": "Cause",
"ref_id": "10377075_T4"
}
]
},
{
"id": "10377075_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
804,
811
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T7"
}
]
},
{
"id": "10377075_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"activators"
],
"offsets": [
[
877,
887
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T8"
}
]
},
{
"id": "10377075_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
911,
920
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_E10"
}
]
},
{
"id": "10377075_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
931,
938
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T10"
},
{
"role": "Cause",
"ref_id": "10377075_T9"
}
]
},
{
"id": "10377075_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
1065,
1074
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_E12"
}
]
},
{
"id": "10377075_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1084,
1091
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_E13"
}
]
},
{
"id": "10377075_E13",
"type": "Transcription",
"trigger": {
"text": [
"mRNA expression"
],
"offsets": [
[
1099,
1114
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T13"
}
]
},
{
"id": "10377075_E14",
"type": "Regulation",
"trigger": {
"text": [
"altering"
],
"offsets": [
[
1123,
1131
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T13"
}
]
},
{
"id": "10377075_E15",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1299,
1312
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T15"
}
]
},
{
"id": "10377075_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
1467,
1474
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T17"
}
]
},
{
"id": "10377075_E17",
"type": "Regulation",
"trigger": {
"text": [
"transcriptional control"
],
"offsets": [
[
1549,
1572
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_E18"
},
{
"role": "Cause",
"ref_id": "10377075_T17"
}
]
},
{
"id": "10377075_E18",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1588,
1598
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T18"
}
]
},
{
"id": "10377075_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"activate"
],
"offsets": [
[
1719,
1727
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10377075_T19"
}
]
}
] | [
{
"id": "10377075_1",
"entity_ids": [
"10377075_T5",
"10377075_T6"
]
},
{
"id": "10377075_2",
"entity_ids": [
"10377075_T2",
"10377075_T3"
]
}
] | [] |
1470918 | 1470918 | [
{
"id": "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": "1470918_T1",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
24,
29
]
],
"normalized": []
},
{
"id": "1470918_T2",
"type": "Protein",
"text": [
"v-Fos"
],
"offsets": [
[
39,
44
]
],
"normalized": []
},
{
"id": "1470918_T3",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
87,
92
]
],
"normalized": []
},
{
"id": "1470918_T4",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
123,
128
]
],
"normalized": []
},
{
"id": "1470918_T5",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
133,
138
]
],
"normalized": []
},
{
"id": "1470918_T6",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
367,
372
]
],
"normalized": []
},
{
"id": "1470918_T7",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
522,
527
]
],
"normalized": []
},
{
"id": "1470918_T8",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
593,
598
]
],
"normalized": []
},
{
"id": "1470918_T9",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
600,
605
]
],
"normalized": []
},
{
"id": "1470918_T10",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
671,
676
]
],
"normalized": []
},
{
"id": "1470918_T11",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
714,
719
]
],
"normalized": []
},
{
"id": "1470918_T12",
"type": "Protein",
"text": [
"v-Fos"
],
"offsets": [
[
780,
785
]
],
"normalized": []
},
{
"id": "1470918_T13",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
825,
830
]
],
"normalized": []
},
{
"id": "1470918_T14",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
879,
884
]
],
"normalized": []
}
] | [
{
"id": "1470918_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"Targeted"
],
"offsets": [
[
0,
8
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E4"
}
]
},
{
"id": "1470918_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"Targeted"
],
"offsets": [
[
0,
8
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E3"
}
]
},
{
"id": "1470918_E3",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
9,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T2"
}
]
},
{
"id": "1470918_E4",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
9,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T1"
}
]
},
{
"id": "1470918_E5",
"type": "Binding",
"trigger": {
"text": [
"heterodimerize"
],
"offsets": [
[
139,
153
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T4"
},
{
"role": "Theme",
"ref_id": "1470918_T5"
}
]
},
{
"id": "1470918_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"through"
],
"offsets": [
[
154,
161
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E5"
}
]
},
{
"id": "1470918_E7",
"type": "Protein_catabolism",
"trigger": {
"text": [
"stability"
],
"offsets": [
[
354,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T6"
}
]
},
{
"id": "1470918_E8",
"type": "Regulation",
"trigger": {
"text": [
"controlled"
],
"offsets": [
[
394,
404
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E7"
}
]
},
{
"id": "1470918_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
532,
541
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T7"
}
]
},
{
"id": "1470918_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"when"
],
"offsets": [
[
542,
546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E9"
},
{
"role": "Cause",
"ref_id": "1470918_E11"
}
]
},
{
"id": "1470918_E11",
"type": "Binding",
"trigger": {
"text": [
"dimerized"
],
"offsets": [
[
563,
572
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T7"
},
{
"role": "Theme",
"ref_id": "1470918_T8"
}
]
},
{
"id": "1470918_E12",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
578,
592
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T8"
}
]
},
{
"id": "1470918_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"target"
],
"offsets": [
[
664,
670
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E14"
},
{
"role": "Cause",
"ref_id": "1470918_T9"
}
]
},
{
"id": "1470918_E14",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
681,
692
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T10"
}
]
},
{
"id": "1470918_E15",
"type": "Protein_catabolism",
"trigger": {
"text": [
"stabilized"
],
"offsets": [
[
735,
745
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T11"
}
]
},
{
"id": "1470918_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"after"
],
"offsets": [
[
746,
751
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_E15"
}
]
},
{
"id": "1470918_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"susceptible"
],
"offsets": [
[
840,
851
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T12"
}
]
},
{
"id": "1470918_E18",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
855,
866
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T12"
}
]
},
{
"id": "1470918_E19",
"type": "Binding",
"trigger": {
"text": [
"targeted"
],
"offsets": [
[
867,
875
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1470918_T12"
},
{
"role": "Theme",
"ref_id": "1470918_T14"
}
]
}
] | [] | [] |
10087185 | 10087185 | [
{
"id": "10087185__text",
"type": "abstract",
"text": [
"Decreased proteasome-mediated degradation in T cells from the elderly: A role in immune senescence. \nInduction of NFkappaB is a highly regulated process requiring phosphorylation, ubiquitination, and proteasome-mediated degradation of the cytosolic inhibitor IkappaBalpha. Analyses of the regulation of IkappaBalpha in TNF-alpha-treated T lymphocytes from young and elderly donors revealed severely compromised degradation of IkappaBalpha in T cells from the elderly. Examination of activation-induced phosphorylation and ubiquitination of IkappaBalpha did not demonstrate any significant age-related alterations. However, examination of proteasome activity in these T cells using fluorogenic peptide assays revealed a significant age-related decline in chymotryptic activity. These results suggest that a decline in proteasome activity results in a failure to fully degrade IkappaBalpha in the elderly. This failure to degrade IkappaBalpha may underlie both the observed decrease in NFkappaB induction and the IL-2 receptor expression in TNF-treated T cells during aging. Thus, decreased proteasome-mediated degradation may be central to immune dysfunction that accompanies aging. Copyright 1999 Academic Press. "
],
"offsets": [
[
0,
1213
]
]
}
] | [
{
"id": "10087185_T1",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
259,
271
]
],
"normalized": []
},
{
"id": "10087185_T2",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
303,
315
]
],
"normalized": []
},
{
"id": "10087185_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
319,
328
]
],
"normalized": []
},
{
"id": "10087185_T4",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
426,
438
]
],
"normalized": []
},
{
"id": "10087185_T5",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
540,
552
]
],
"normalized": []
},
{
"id": "10087185_T6",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
875,
887
]
],
"normalized": []
},
{
"id": "10087185_T7",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
928,
940
]
],
"normalized": []
}
] | [
{
"id": "10087185_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
211,
219
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_E2"
}
]
},
{
"id": "10087185_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
220,
231
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_T1"
}
]
},
{
"id": "10087185_E3",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
289,
299
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_T2"
}
]
},
{
"id": "10087185_E4",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
411,
422
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_T4"
}
]
},
{
"id": "10087185_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
494,
501
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_E6"
}
]
},
{
"id": "10087185_E6",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
502,
517
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_T5"
}
]
},
{
"id": "10087185_E7",
"type": "Regulation",
"trigger": {
"text": [
"alterations"
],
"offsets": [
[
601,
612
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_E5"
}
]
},
{
"id": "10087185_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"results"
],
"offsets": [
[
837,
844
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_E9"
}
]
},
{
"id": "10087185_E9",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degrade"
],
"offsets": [
[
867,
874
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_T6"
}
]
},
{
"id": "10087185_E10",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degrade"
],
"offsets": [
[
920,
927
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10087185_T7"
}
]
}
] | [] | [] |
8067997 | 8067997 | [
{
"id": "8067997__text",
"type": "abstract",
"text": [
"Inhibition of activation of transcription factor AP-1 by CD28 signalling in human T-cells. \nCo-stimulation of T-lymphocytes by T-cell receptor (TcR) occupancy and activation of the CD28 surface molecule results in enhanced proliferation and interleukin 2 (IL-2) production. The increase in IL-2 gene expression triggered by CD28 involves a kappa B-like sequence in the 5'-regulatory region of the IL-2 promoter, called CD28-responsive element. Stimulation of T-cells by agonistic anti-CD28 antibodies in conjunction with phorbol 12-myristate 13-acetate (PMA)- or TcR-derived signals induces the enhanced activation of the transcription factor NF-kappa B. Here we report that CD28 engagement, however, exerts opposite effects on the transcription factor AP-1. Whereas anti-CD28 together with PMA increased the DNA binding and trans-activation activity of NF-kappa B, PMA-induced activation of AP-1 was significantly suppressed. The inhibitory effect exerted by anti-CD28 was observed at the level of DNA binding as well as in functional reporter-gene assays. These results suggest that the two transcription factors are independently regulated and may perform different functions during T-cell activation. "
],
"offsets": [
[
0,
1205
]
]
}
] | [
{
"id": "8067997_T1",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
57,
61
]
],
"normalized": []
},
{
"id": "8067997_T2",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
181,
185
]
],
"normalized": []
},
{
"id": "8067997_T3",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
241,
254
]
],
"normalized": []
},
{
"id": "8067997_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
256,
260
]
],
"normalized": []
},
{
"id": "8067997_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
290,
294
]
],
"normalized": []
},
{
"id": "8067997_T6",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
324,
328
]
],
"normalized": []
},
{
"id": "8067997_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
397,
401
]
],
"normalized": []
},
{
"id": "8067997_T8",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
419,
423
]
],
"normalized": []
},
{
"id": "8067997_T9",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
485,
489
]
],
"normalized": []
},
{
"id": "8067997_T10",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
675,
679
]
],
"normalized": []
},
{
"id": "8067997_T11",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
772,
776
]
],
"normalized": []
},
{
"id": "8067997_T12",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
965,
969
]
],
"normalized": []
}
] | [
{
"id": "8067997_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
163,
173
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8067997_T2"
}
]
},
{
"id": "8067997_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
262,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8067997_T4"
}
]
},
{
"id": "8067997_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
278,
286
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8067997_E4"
},
{
"role": "Cause",
"ref_id": "8067997_T6"
}
]
},
{
"id": "8067997_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
300,
310
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8067997_T5"
}
]
},
{
"id": "8067997_E5",
"type": "Binding",
"trigger": {
"text": [
"engagement"
],
"offsets": [
[
680,
690
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8067997_T10"
}
]
}
] | [
{
"id": "8067997_1",
"entity_ids": [
"8067997_T3",
"8067997_T4"
]
}
] | [] |
8691123 | 8691123 | [
{
"id": "8691123__text",
"type": "abstract",
"text": [
"Activation protein 1-dependent transcriptional activation of interleukin 2 gene by Ca2+/calmodulin kinase type IV/Gr. \nThe Ca2+/calmodulin-dependent protein kinase (CaMK) type IV/Gr is selectively expressed in T lymphocytes and is activated after signaling via the T cell antigen receptor (TCR), indicating that it mediates some of the Ca(2+)-dependent transcriptional events that follow TCR engagement. Here we show that CaMKIV/Gr induces the transcription factor activation protein 1 (AP-1) alone or in synergy with T cell mitogens and with the p21ras oncoprotein. CaMKIV/ Gr signaling is associated with transcriptional activation of c-fos but is independent of p21ras or calcineurin. AP-1 is an integral component of the nuclear factor of activated T cells (NFAT) transcriptional complex, which is required for interleukin 2 gene expression in T cells. We demonstrate that CaMKIV/Gr reconstitutes the capacity of the cytosolic component of NFAT to direct transcription from NFAT sites in non-T cells. These results reveal a central role for CaMKIV/Gr as a Ca(2+)-regulated activator of gene transcription in T lymphocytes. "
],
"offsets": [
[
0,
1127
]
]
}
] | [
{
"id": "8691123_T1",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
61,
74
]
],
"normalized": []
},
{
"id": "8691123_T2",
"type": "Protein",
"text": [
"Ca2+/calmodulin kinase type IV/Gr"
],
"offsets": [
[
83,
116
]
],
"normalized": []
},
{
"id": "8691123_T3",
"type": "Protein",
"text": [
"Ca2+/calmodulin-dependent protein kinase (CaMK) type IV/Gr"
],
"offsets": [
[
123,
181
]
],
"normalized": []
},
{
"id": "8691123_T4",
"type": "Protein",
"text": [
"CaMKIV/Gr"
],
"offsets": [
[
422,
431
]
],
"normalized": []
},
{
"id": "8691123_T5",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
547,
553
]
],
"normalized": []
},
{
"id": "8691123_T6",
"type": "Protein",
"text": [
"CaMKIV/ Gr"
],
"offsets": [
[
567,
577
]
],
"normalized": []
},
{
"id": "8691123_T7",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
637,
642
]
],
"normalized": []
},
{
"id": "8691123_T8",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
665,
671
]
],
"normalized": []
},
{
"id": "8691123_T9",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
815,
828
]
],
"normalized": []
},
{
"id": "8691123_T10",
"type": "Protein",
"text": [
"CaMKIV/Gr"
],
"offsets": [
[
877,
886
]
],
"normalized": []
},
{
"id": "8691123_T11",
"type": "Protein",
"text": [
"CaMKIV/Gr"
],
"offsets": [
[
1045,
1054
]
],
"normalized": []
}
] | [
{
"id": "8691123_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
21,
30
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_E2"
}
]
},
{
"id": "8691123_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"transcriptional activation"
],
"offsets": [
[
31,
57
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_T1"
},
{
"role": "Cause",
"ref_id": "8691123_T2"
}
]
},
{
"id": "8691123_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
197,
206
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_T3"
}
]
},
{
"id": "8691123_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
231,
240
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_E3"
}
]
},
{
"id": "8691123_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"transcriptional activation"
],
"offsets": [
[
607,
633
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_T7"
}
]
},
{
"id": "8691123_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
802,
810
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_E7"
}
]
},
{
"id": "8691123_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
834,
844
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8691123_T9"
}
]
}
] | [] | [] |
9376579 | 9376579 | [
{
"id": "9376579__text",
"type": "abstract",
"text": [
"Modulation of mRNA expression of a novel human myeloid-selective CCAAT/enhancer binding protein gene (C/EBP epsilon). \nHuman C/EBP epsilon is a newly cloned gene coding for a CCAAT/enhancer binding protein that may be involved in the regulation of myeloid differentiation. Our studies showed that levels of C/EBP epsilon mRNA were markedly increased in NB4 cells (promyelocytic leukemia line), because they were induced by 9-cis retinoic acid (9-cis RA) to differentiate towards granulocytes. Accumulation of C/EBP epsilon mRNA occurred as early as 1 hour after exposure of NB4 cells to 9-cis RA (5 x 10(-7) mol/L); and at 48 hours, levels were increased by 5.1-fold. Dose-response studies showed that 10(-7) to 10(-6) mol/L 9-cis RA (12 hours) resulted in peak levels of C/EBP epsilon mRNA; but even 10(-10) mol/L 9-cis RA increased levels of these transcripts. NB4 cells pulse-exposed (30 minutes) to all-trans retinoic acid (ATRA), washed, and cultured (3 days) with either dimethylsulfoxide (DMSO) or hexamethylene bisacetamide (HMBA) had a prominent increase in levels of C/EBP epsilon mRNA and an increase in granulocytic differentiation, but exposure to either DMSO or HMBA alone had no effect on base levels of C/EBP epsilon and did not induce differentiation. Macrophage-differentiation of NB4 reduced levels of C/EBP epsilon mRNA. Nuclear run-off assays and half-life studies showed that accumulation of C/EBP epsilon mRNA by 9-cis RA was due to enhanced transcription. Furthermore, this C/EBP epsilon mRNA accumulation did not require synthesis of new protein factors because 9-cis RA induced C/EBP epsilon mRNA accumulation in the absence of new protein synthesis. ATRA also induced expression of C/EBP epsilon protein in NB4 cells, as shown by Western blotting. In contrast to the increase of C/EBP epsilon in 9-cis RA-mediated granulocytic differentiation, the DMSO-induced differentiation of HL-60 cells down the granulocytic pathway was associated with an initial reduction of C/EBP epsilon mRNA levels. In summary, we have discovered that expression of C/EBP epsilon mRNA is markedly enhanced as the NB4 promyelocytes are induced by retinoids to differentiate towards granulocytes. This induction of C/EBP epsilon mRNA expression is transcriptionally mediated and occurs in the absence of synthesis of additional protein factors. We suspect that the C/EBP epsilon promoter/enhancer contains a retinoic acid-response element that is directly stimulated by retinoids. "
],
"offsets": [
[
0,
2483
]
]
}
] | [
{
"id": "9376579_T1",
"type": "Protein",
"text": [
"CCAAT/enhancer binding protein"
],
"offsets": [
[
65,
95
]
],
"normalized": []
},
{
"id": "9376579_T2",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
102,
115
]
],
"normalized": []
},
{
"id": "9376579_T3",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
125,
138
]
],
"normalized": []
},
{
"id": "9376579_T4",
"type": "Protein",
"text": [
"CCAAT/enhancer binding protein"
],
"offsets": [
[
175,
205
]
],
"normalized": []
},
{
"id": "9376579_T5",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
307,
320
]
],
"normalized": []
},
{
"id": "9376579_T6",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
509,
522
]
],
"normalized": []
},
{
"id": "9376579_T7",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
772,
785
]
],
"normalized": []
},
{
"id": "9376579_T8",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1077,
1090
]
],
"normalized": []
},
{
"id": "9376579_T9",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1219,
1232
]
],
"normalized": []
},
{
"id": "9376579_T10",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1321,
1334
]
],
"normalized": []
},
{
"id": "9376579_T11",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1414,
1427
]
],
"normalized": []
},
{
"id": "9376579_T12",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1498,
1511
]
],
"normalized": []
},
{
"id": "9376579_T13",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1604,
1617
]
],
"normalized": []
},
{
"id": "9376579_T14",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1709,
1722
]
],
"normalized": []
},
{
"id": "9376579_T15",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1806,
1819
]
],
"normalized": []
},
{
"id": "9376579_T16",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
1993,
2006
]
],
"normalized": []
},
{
"id": "9376579_T17",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
2070,
2083
]
],
"normalized": []
},
{
"id": "9376579_T18",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
2217,
2230
]
],
"normalized": []
},
{
"id": "9376579_T19",
"type": "Protein",
"text": [
"C/EBP epsilon"
],
"offsets": [
[
2367,
2380
]
],
"normalized": []
},
{
"id": "9376579_T48",
"type": "Entity",
"text": [
"retinoic acid-response element"
],
"offsets": [
[
2410,
2440
]
],
"normalized": []
}
] | [
{
"id": "9376579_E1",
"type": "Regulation",
"trigger": {
"text": [
"Modulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E2"
}
]
},
{
"id": "9376579_E2",
"type": "Transcription",
"trigger": {
"text": [
"mRNA expression"
],
"offsets": [
[
14,
29
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T2"
}
]
},
{
"id": "9376579_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
340,
349
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T5"
}
]
},
{
"id": "9376579_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
412,
419
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T5"
}
]
},
{
"id": "9376579_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"occurred"
],
"offsets": [
[
528,
536
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T6"
}
]
},
{
"id": "9376579_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
645,
654
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T6"
}
]
},
{
"id": "9376579_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"resulted in peak levels"
],
"offsets": [
[
745,
768
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T7"
}
]
},
{
"id": "9376579_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased levels"
],
"offsets": [
[
824,
840
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T7"
}
]
},
{
"id": "9376579_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"had a prominent increase"
],
"offsets": [
[
1039,
1063
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T8"
}
]
},
{
"id": "9376579_E10",
"type": "Regulation",
"trigger": {
"text": [
"had no effect"
],
"offsets": [
[
1187,
1200
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T9"
}
]
},
{
"id": "9376579_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
1303,
1310
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T10"
}
]
},
{
"id": "9376579_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"accumulation"
],
"offsets": [
[
1398,
1410
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T11"
}
]
},
{
"id": "9376579_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"due to"
],
"offsets": [
[
1449,
1455
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E12"
},
{
"role": "Cause",
"ref_id": "9376579_E14"
}
]
},
{
"id": "9376579_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
1456,
1464
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E15"
}
]
},
{
"id": "9376579_E15",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1465,
1478
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T11"
}
]
},
{
"id": "9376579_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"accumulation"
],
"offsets": [
[
1517,
1529
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T12"
}
]
},
{
"id": "9376579_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"not require"
],
"offsets": [
[
1534,
1545
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E16"
}
]
},
{
"id": "9376579_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1596,
1603
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E19"
}
]
},
{
"id": "9376579_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"accumulation"
],
"offsets": [
[
1623,
1635
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T13"
}
]
},
{
"id": "9376579_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1687,
1694
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E21"
}
]
},
{
"id": "9376579_E21",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1695,
1705
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T14"
}
]
},
{
"id": "9376579_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1794,
1802
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T15"
}
]
},
{
"id": "9376579_E23",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduction"
],
"offsets": [
[
1980,
1989
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T16"
}
]
},
{
"id": "9376579_E24",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
2056,
2066
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T17"
}
]
},
{
"id": "9376579_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
2101,
2109
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E24"
}
]
},
{
"id": "9376579_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
2204,
2213
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E27"
}
]
},
{
"id": "9376579_E27",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
2236,
2246
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T18"
}
]
},
{
"id": "9376579_E28",
"type": "Positive_regulation",
"trigger": {
"text": [
"transcriptionally mediated"
],
"offsets": [
[
2250,
2276
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_E26"
}
]
},
{
"id": "9376579_E29",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
2458,
2468
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9376579_T19"
},
{
"role": "Site",
"ref_id": "9376579_T48"
}
]
}
] | [] | [] |
7884865 | 7884865 | [
{
"id": "7884865__text",
"type": "abstract",
"text": [
"LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha. \nLMP-1, an Epstein-Barr virus membrane protein expressed during latent infection, has oncogenic properties, as judged from its ability to transform B lymphocytes and rodent fibroblasts. LMP-1 induces the expression of bcl2, an oncogene which protects cells from apoptosis, as well as of genes encoding other proteins involved in cell regulation and growth control. The mechanisms by which LMP-1 upregulates these proteins is unknown, but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes. NF-kappa B, a transcription factor controlling the expression of genes involved in cell activation and growth control, has been shown to be activated by LMP-1. The mechanism(s) regulating this activation remains unknown. Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1. I kappa B alpha is selectively modified in LMP-1-expressing B cells. A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation. This results in increased transcription of NF-kappa B-dependent-genes, including those encoding p105 and I kappa B alpha (MAD3). These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha. Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis. "
],
"offsets": [
[
0,
1760
]
]
}
] | [
{
"id": "7884865_T1",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "7884865_T2",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
64,
79
]
],
"normalized": []
},
{
"id": "7884865_T3",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
82,
87
]
],
"normalized": []
},
{
"id": "7884865_T4",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
267,
272
]
],
"normalized": []
},
{
"id": "7884865_T5",
"type": "Protein",
"text": [
"bcl2"
],
"offsets": [
[
299,
303
]
],
"normalized": []
},
{
"id": "7884865_T6",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
470,
475
]
],
"normalized": []
},
{
"id": "7884865_T7",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
540,
545
]
],
"normalized": []
},
{
"id": "7884865_T8",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
863,
868
]
],
"normalized": []
},
{
"id": "7884865_T9",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
1076,
1081
]
],
"normalized": []
},
{
"id": "7884865_T10",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1083,
1098
]
],
"normalized": []
},
{
"id": "7884865_T11",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
1126,
1131
]
],
"normalized": []
},
{
"id": "7884865_T12",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1177,
1192
]
],
"normalized": []
},
{
"id": "7884865_T13",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1391,
1395
]
],
"normalized": []
},
{
"id": "7884865_T14",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1400,
1415
]
],
"normalized": []
},
{
"id": "7884865_T15",
"type": "Protein",
"text": [
"MAD3"
],
"offsets": [
[
1417,
1421
]
],
"normalized": []
},
{
"id": "7884865_T16",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
1452,
1457
]
],
"normalized": []
},
{
"id": "7884865_T17",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1508,
1523
]
],
"normalized": []
},
{
"id": "7884865_T18",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
1569,
1574
]
],
"normalized": []
},
{
"id": "7884865_T19",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1623,
1638
]
],
"normalized": []
}
] | [
{
"id": "7884865_E1",
"type": "Regulation",
"trigger": {
"text": [
"targeting"
],
"offsets": [
[
30,
39
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T2"
},
{
"role": "Cause",
"ref_id": "7884865_T1"
}
]
},
{
"id": "7884865_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
128,
137
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T3"
}
]
},
{
"id": "7884865_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
273,
280
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_E4"
},
{
"role": "Cause",
"ref_id": "7884865_T4"
}
]
},
{
"id": "7884865_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
285,
295
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T5"
}
]
},
{
"id": "7884865_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulates"
],
"offsets": [
[
476,
487
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T5"
},
{
"role": "Cause",
"ref_id": "7884865_T6"
}
]
},
{
"id": "7884865_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
1065,
1075
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T9"
}
]
},
{
"id": "7884865_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
1132,
1142
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T11"
}
]
},
{
"id": "7884865_E8",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated form"
],
"offsets": [
[
1154,
1173
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T12"
}
]
},
{
"id": "7884865_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1311,
1320
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_E12"
}
]
},
{
"id": "7884865_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1311,
1320
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_E11"
}
]
},
{
"id": "7884865_E11",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1321,
1334
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T15"
}
]
},
{
"id": "7884865_E12",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1321,
1334
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T13"
}
]
},
{
"id": "7884865_E13",
"type": "Regulation",
"trigger": {
"text": [
"targeting"
],
"offsets": [
[
1498,
1507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7884865_T17"
},
{
"role": "Cause",
"ref_id": "7884865_T16"
}
]
}
] | [
{
"id": "7884865_1",
"entity_ids": [
"7884865_T14",
"7884865_T15"
]
}
] | [] |
7878466 | 7878466 | [
{
"id": "7878466__text",
"type": "abstract",
"text": [
"Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. \nI kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B. "
],
"offsets": [
[
0,
845
]
]
}
] | [
{
"id": "7878466_T1",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
11,
26
]
],
"normalized": []
},
{
"id": "7878466_T2",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
90,
105
]
],
"normalized": []
},
{
"id": "7878466_T3",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
270,
285
]
],
"normalized": []
},
{
"id": "7878466_T4",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
482,
497
]
],
"normalized": []
},
{
"id": "7878466_T5",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
584,
599
]
],
"normalized": []
},
{
"id": "7878466_T13",
"type": "Entity",
"text": [
"serine-32"
],
"offsets": [
[
558,
567
]
],
"normalized": []
},
{
"id": "7878466_T14",
"type": "Entity",
"text": [
"serine-36"
],
"offsets": [
[
571,
580
]
],
"normalized": []
}
] | [
{
"id": "7878466_E1",
"type": "Regulation",
"trigger": {
"text": [
"Control"
],
"offsets": [
[
0,
7
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_E2"
},
{
"role": "Cause",
"ref_id": "7878466_E3"
}
]
},
{
"id": "7878466_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"proteolysis"
],
"offsets": [
[
27,
38
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T1"
}
]
},
{
"id": "7878466_E3",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
72,
87
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T1"
}
]
},
{
"id": "7878466_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inactivate"
],
"offsets": [
[
259,
269
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T3"
}
]
},
{
"id": "7878466_E5",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
463,
478
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T4"
}
]
},
{
"id": "7878466_E6",
"type": "Regulation",
"trigger": {
"text": [
"requires"
],
"offsets": [
[
502,
510
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_E7"
}
]
},
{
"id": "7878466_E7",
"type": "Protein_catabolism",
"trigger": {
"text": [
"proteolysis"
],
"offsets": [
[
515,
526
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T4"
}
]
},
{
"id": "7878466_E8",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
656,
671
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T5"
},
{
"role": "Site",
"ref_id": "7878466_T14"
}
]
},
{
"id": "7878466_E9",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
656,
671
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T5"
},
{
"role": "Site",
"ref_id": "7878466_T13"
}
]
},
{
"id": "7878466_E10",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
675,
686
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T5"
}
]
},
{
"id": "7878466_E11",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
754,
769
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T5"
},
{
"role": "Site",
"ref_id": "7878466_T14"
}
]
},
{
"id": "7878466_E12",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
754,
769
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7878466_T5"
},
{
"role": "Site",
"ref_id": "7878466_T13"
}
]
}
] | [] | [] |
8566023 | 8566023 | [
{
"id": "8566023__text",
"type": "abstract",
"text": [
"Identification of an ionomycin/cyclosporin A-responsive element within the human T cell receptor gamma enhancer. \nActivation through the Ca2+/calcineurin pathway is essential to the transcription of many cytokine genes. The conserved cis-acting sequence, GGAAAA, and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations. Here we report the identification and importance of the same sequence in a non-cytokine gene, the human T cell receptor gamma (TCRG) enhancer. Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin-induced activation of the TCRG enhancer. Our studies provide an explanation for a previous observation that TCRG mRNA levels, but not mRNA levels for T cell receptor alpha and -beta, are increased by ionomycin treatment. "
],
"offsets": [
[
0,
893
]
]
}
] | [
{
"id": "8566023_T1",
"type": "Protein",
"text": [
"T cell receptor gamma"
],
"offsets": [
[
81,
102
]
],
"normalized": []
},
{
"id": "8566023_T2",
"type": "Protein",
"text": [
"T cell receptor gamma"
],
"offsets": [
[
495,
516
]
],
"normalized": []
},
{
"id": "8566023_T3",
"type": "Protein",
"text": [
"TCRG"
],
"offsets": [
[
518,
522
]
],
"normalized": []
},
{
"id": "8566023_T4",
"type": "Protein",
"text": [
"TCRG"
],
"offsets": [
[
698,
702
]
],
"normalized": []
},
{
"id": "8566023_T5",
"type": "Protein",
"text": [
"TCRG"
],
"offsets": [
[
780,
784
]
],
"normalized": []
},
{
"id": "8566023_T8",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
703,
711
]
],
"normalized": []
}
] | [
{
"id": "8566023_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediates"
],
"offsets": [
[
649,
657
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8566023_E2"
}
]
},
{
"id": "8566023_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
680,
690
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8566023_T4"
},
{
"role": "Site",
"ref_id": "8566023_T8"
}
]
},
{
"id": "8566023_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
859,
868
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8566023_T5"
}
]
}
] | [
{
"id": "8566023_1",
"entity_ids": [
"8566023_T2",
"8566023_T3"
]
}
] | [] |
9135552 | 9135552 | [
{
"id": "9135552__text",
"type": "abstract",
"text": [
"The tumour associated cell surface antigen A6H is costimulatory for human CD4+ but not CD8+ T cells. \nThe A6H monoclonal antibody (mAb) recognizes a 120,000-140,000 MW antigen that is expressed at similar densities on 85-90% of human CD4+ and CD8+ T cells and on renal cell carcinomas. The binding of the A6H mAb induced a costimulatory signal in anti-CD3 activated T cells. In the present report, we show that A6H costimulated cell proliferation and cytokine production in purified CD4+ T cells. Unexpectedly, the CD8+ T-cell subpopulation failed to respond. CD4+ T cells costimulated with the A6H mAb upregulated CD80, CD86, CD71, interleukin-2 (IL-2)R alpha, IL-2R beta and IL-2R gamma, while no corresponding up-regulation of these cell surface molecules was seen in CD8+ T cells. In order to investigate the nature of the A6H mAb costimulus at the transcriptional level we have examined induction of the transcription factors OCT-1, AP-1 and NF-kappa B which are known to be transcriptional regulators of several cytokine and cytokine receptor genes, including the IL-2 and IL-2R genes. Co-ligation of the A6H antigen and the CD3 complex induced expression of the transcription factor AP-1 in CD4+ T cells, whereas no increase in NF-kappa B and octamer-binding (Oct) proteins was seen compared to T cells stimulated with anti-CD3 alone. Furthermore, no induction of AP-1 was seen in A6H costimulated CD8+ T cells. These results suggests that both proximal steps in CD8+ T-cell activation as well as the later phases are unresponsive to A6H ligation. Molecular differences of the A6H molecule or distinct regulation of the A6H transduced AP-1 activation pathway may exist in CD4+ and CD8+ T cell subpopulations. "
],
"offsets": [
[
0,
1716
]
]
}
] | [
{
"id": "9135552_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
74,
77
]
],
"normalized": []
},
{
"id": "9135552_T2",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
234,
237
]
],
"normalized": []
},
{
"id": "9135552_T3",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
483,
486
]
],
"normalized": []
},
{
"id": "9135552_T4",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
560,
563
]
],
"normalized": []
},
{
"id": "9135552_T5",
"type": "Protein",
"text": [
"CD80"
],
"offsets": [
[
615,
619
]
],
"normalized": []
},
{
"id": "9135552_T6",
"type": "Protein",
"text": [
"CD86"
],
"offsets": [
[
621,
625
]
],
"normalized": []
},
{
"id": "9135552_T7",
"type": "Protein",
"text": [
"CD71"
],
"offsets": [
[
627,
631
]
],
"normalized": []
},
{
"id": "9135552_T8",
"type": "Protein",
"text": [
"interleukin-2 (IL-2)R alpha"
],
"offsets": [
[
633,
660
]
],
"normalized": []
},
{
"id": "9135552_T9",
"type": "Protein",
"text": [
"IL-2R beta"
],
"offsets": [
[
662,
672
]
],
"normalized": []
},
{
"id": "9135552_T10",
"type": "Protein",
"text": [
"IL-2R gamma"
],
"offsets": [
[
677,
688
]
],
"normalized": []
},
{
"id": "9135552_T11",
"type": "Protein",
"text": [
"OCT-1"
],
"offsets": [
[
931,
936
]
],
"normalized": []
},
{
"id": "9135552_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1070,
1074
]
],
"normalized": []
},
{
"id": "9135552_T13",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1198,
1201
]
],
"normalized": []
},
{
"id": "9135552_T14",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1679,
1682
]
],
"normalized": []
}
] | [
{
"id": "9135552_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
603,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T7"
}
]
},
{
"id": "9135552_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
603,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T5"
}
]
},
{
"id": "9135552_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
603,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T10"
}
]
},
{
"id": "9135552_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
603,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T6"
}
]
},
{
"id": "9135552_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
603,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T9"
}
]
},
{
"id": "9135552_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
603,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T8"
}
]
},
{
"id": "9135552_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
713,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T5"
}
]
},
{
"id": "9135552_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
713,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T9"
}
]
},
{
"id": "9135552_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
713,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T8"
}
]
},
{
"id": "9135552_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
713,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T6"
}
]
},
{
"id": "9135552_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
713,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T10"
}
]
},
{
"id": "9135552_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
713,
726
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T7"
}
]
},
{
"id": "9135552_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
892,
901
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T11"
}
]
},
{
"id": "9135552_E14",
"type": "Regulation",
"trigger": {
"text": [
"transcriptional regulators"
],
"offsets": [
[
980,
1006
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T12"
}
]
},
{
"id": "9135552_E15",
"type": "Regulation",
"trigger": {
"text": [
"transcriptional regulators"
],
"offsets": [
[
980,
1006
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9135552_T12"
},
{
"role": "Cause",
"ref_id": "9135552_T11"
}
]
}
] | [] | [] |
10072497 | 10072497 | [
{
"id": "10072497__text",
"type": "abstract",
"text": [
"N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level: association with NF-kappaB inhibition. \nN-acetyl-L-cysteine (NAC) is an antioxidant molecule endowed with immunomodulatory properties. To investigate the effect of NAC on the induction phase of T cell responses, we analyzed its action on human dendritic cells (DC) derived from adherent PBMC cultured with IL-4 and granulocyte-macrophage CSF. We first found that NAC inhibited the constitutive as well as the LPS-induced activity of the transcription factor NF-kappaB. In parallel, NAC was shown to down-regulate the production of cytokines by DC as well as their surface expression of HLA-DR, CD86 (B7-2), and CD40 molecules both at the basal state and upon LPS activation. NAC also inhibited DC responses induced by CD40 engagement. The inhibitory effects of NAC were not due to nonspecific toxicity as neither the viability of DC nor their mannose receptor-mediated endocytosis were modified by NAC. Finally, we found that the addition of NAC to MLR between naive T cells and allogeneic DC resulted in a profound inhibition of alloreactive responses, which could be attributed to a defect of DC as APC-independent T cell responses were not inhibited by NAC. Altogether, our results suggest that NAC might impair the generation of primary immune responses in humans through its inhibitory action on DC. "
],
"offsets": [
[
0,
1394
]
]
}
] | [
{
"id": "10072497_T1",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
395,
399
]
],
"normalized": []
},
{
"id": "10072497_T2",
"type": "Protein",
"text": [
"granulocyte-macrophage CSF"
],
"offsets": [
[
404,
430
]
],
"normalized": []
},
{
"id": "10072497_T3",
"type": "Protein",
"text": [
"CD86"
],
"offsets": [
[
683,
687
]
],
"normalized": []
},
{
"id": "10072497_T4",
"type": "Protein",
"text": [
"B7-2"
],
"offsets": [
[
689,
693
]
],
"normalized": []
},
{
"id": "10072497_T5",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
700,
704
]
],
"normalized": []
},
{
"id": "10072497_T6",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
807,
811
]
],
"normalized": []
},
{
"id": "10072497_T7",
"type": "Protein",
"text": [
"mannose receptor"
],
"offsets": [
[
932,
948
]
],
"normalized": []
}
] | [
{
"id": "10072497_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulate"
],
"offsets": [
[
588,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_E5"
}
]
},
{
"id": "10072497_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulate"
],
"offsets": [
[
588,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_E6"
}
]
},
{
"id": "10072497_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulate"
],
"offsets": [
[
588,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_E7"
}
]
},
{
"id": "10072497_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulate"
],
"offsets": [
[
588,
601
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_E8"
}
]
},
{
"id": "10072497_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
661,
671
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_T3"
}
]
},
{
"id": "10072497_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
661,
671
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_T5"
}
]
},
{
"id": "10072497_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
752,
762
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_E5"
}
]
},
{
"id": "10072497_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
752,
762
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_E6"
}
]
},
{
"id": "10072497_E9",
"type": "Binding",
"trigger": {
"text": [
"engagement"
],
"offsets": [
[
812,
822
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10072497_T6"
}
]
}
] | [
{
"id": "10072497_1",
"entity_ids": [
"10072497_T3",
"10072497_T4"
]
}
] | [] |
7905504 | 7905504 | [
{
"id": "7905504__text",
"type": "abstract",
"text": [
"Effects of CD45 on NF-kappa B. Implications for replication of HIV-1. \nIncreased levels of replication of the HIV type 1 are observed after the activation of infected T cells through the TCR. However, anti-CD45 antibodies inhibit these effects in cells from infected individuals. In this study, we examined interrelationships between CD45 and HIV-1 further. We measured effects on the HIV-1 LTR in T cell lines that were stimulated with antibodies against CD45 and in those that lacked the expression of CD45 on their surfaces. First, anti-CD45 antibodies did not affect basal but decreased activated levels of expression from the HIV-1 LTR. Second, T cells, which lack CD45 and cannot signal via the TCR, supported higher levels of viral replication and gene expression. This was due to the presence of active NF-kappa B complexes in the nucleus of CD45- T cells. Additionally, infected T cells displayed lower levels of CD45 on their surfaces. Thus, CD45 plays an active role in the physiology of T cells and in the replication of HIV-1. "
],
"offsets": [
[
0,
1040
]
]
}
] | [
{
"id": "7905504_T1",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
11,
15
]
],
"normalized": []
},
{
"id": "7905504_T2",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
206,
210
]
],
"normalized": []
},
{
"id": "7905504_T3",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
334,
338
]
],
"normalized": []
},
{
"id": "7905504_T4",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
456,
460
]
],
"normalized": []
},
{
"id": "7905504_T5",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
504,
508
]
],
"normalized": []
},
{
"id": "7905504_T6",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
540,
544
]
],
"normalized": []
},
{
"id": "7905504_T7",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
670,
674
]
],
"normalized": []
},
{
"id": "7905504_T8",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
850,
854
]
],
"normalized": []
},
{
"id": "7905504_T9",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
922,
926
]
],
"normalized": []
},
{
"id": "7905504_T10",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
952,
956
]
],
"normalized": []
}
] | [
{
"id": "7905504_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
490,
500
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7905504_T5"
}
]
},
{
"id": "7905504_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"lack"
],
"offsets": [
[
665,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7905504_T7"
}
]
},
{
"id": "7905504_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"displayed lower levels"
],
"offsets": [
[
896,
918
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7905504_T9"
}
]
}
] | [] | [] |
10080948 | 10080948 | [
{
"id": "10080948__text",
"type": "abstract",
"text": [
"Phosphorylation of TRAF2 inhibits binding to the CD40 cytoplasmic domain. \nTRAF2 is a signal transducing adaptor molecule which binds to the CD40 cytoplasmic domain. We have found that it is phosphorylated, predominantly on serine residues, when transiently overexpressed in 293 cells. The phosphorylation appears to be related to the signaling events that are activated by TRAF2 under these circumstances, since two nonfunctional mutants were found to be phosphorylated significantly less than the wild-type protein. Furthermore, the phosphorylation status of TRAF2 had significant effects on the ability of the protein to bind to CD40, as evidenced by our observations that the CD40 cytoplasmic domain interacted preferentially with underphosphorylated TRAF2 and that phosphatase treatment significantly enhanced the binding of TRAF2 to CD40. We conclude from these studies that the phosphorylation of TRAF2 is likely to play an important role in regulating signaling by virtue of its ability to influence the CD40-TRAF2 interaction. Copyright 1999 Academic Press. "
],
"offsets": [
[
0,
1067
]
]
}
] | [
{
"id": "10080948_T1",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
19,
24
]
],
"normalized": []
},
{
"id": "10080948_T2",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
49,
53
]
],
"normalized": []
},
{
"id": "10080948_T3",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
75,
80
]
],
"normalized": []
},
{
"id": "10080948_T4",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
141,
145
]
],
"normalized": []
},
{
"id": "10080948_T5",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
374,
379
]
],
"normalized": []
},
{
"id": "10080948_T6",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
561,
566
]
],
"normalized": []
},
{
"id": "10080948_T7",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
632,
636
]
],
"normalized": []
},
{
"id": "10080948_T8",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
680,
684
]
],
"normalized": []
},
{
"id": "10080948_T9",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
755,
760
]
],
"normalized": []
},
{
"id": "10080948_T10",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
830,
835
]
],
"normalized": []
},
{
"id": "10080948_T11",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
839,
843
]
],
"normalized": []
},
{
"id": "10080948_T12",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
904,
909
]
],
"normalized": []
},
{
"id": "10080948_T13",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
1012,
1016
]
],
"normalized": []
},
{
"id": "10080948_T14",
"type": "Protein",
"text": [
"TRAF2"
],
"offsets": [
[
1017,
1022
]
],
"normalized": []
},
{
"id": "10080948_T18",
"type": "Entity",
"text": [
"cytoplasmic domain"
],
"offsets": [
[
54,
72
]
],
"normalized": []
},
{
"id": "10080948_T20",
"type": "Entity",
"text": [
"cytoplasmic domain"
],
"offsets": [
[
146,
164
]
],
"normalized": []
},
{
"id": "10080948_T22",
"type": "Entity",
"text": [
"serine residues"
],
"offsets": [
[
224,
239
]
],
"normalized": []
},
{
"id": "10080948_T29",
"type": "Entity",
"text": [
"cytoplasmic domain"
],
"offsets": [
[
685,
703
]
],
"normalized": []
}
] | [
{
"id": "10080948_E1",
"type": "Phosphorylation",
"trigger": {
"text": [
"Phosphorylation"
],
"offsets": [
[
0,
15
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T1"
}
]
},
{
"id": "10080948_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
25,
33
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E3"
},
{
"role": "Cause",
"ref_id": "10080948_E1"
}
]
},
{
"id": "10080948_E3",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
34,
41
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T1"
},
{
"role": "Theme",
"ref_id": "10080948_T2"
},
{
"role": "Site",
"ref_id": "10080948_T18"
}
]
},
{
"id": "10080948_E4",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
128,
133
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T3"
},
{
"role": "Theme",
"ref_id": "10080948_T4"
},
{
"role": "Site",
"ref_id": "10080948_T20"
}
]
},
{
"id": "10080948_E5",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
191,
205
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T3"
},
{
"role": "Site",
"ref_id": "10080948_T22"
}
]
},
{
"id": "10080948_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"when"
],
"offsets": [
[
241,
245
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E5"
},
{
"role": "Cause",
"ref_id": "10080948_E7"
}
]
},
{
"id": "10080948_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"overexpressed"
],
"offsets": [
[
258,
271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E8"
}
]
},
{
"id": "10080948_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpressed"
],
"offsets": [
[
258,
271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T3"
}
]
},
{
"id": "10080948_E9",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
535,
550
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T6"
}
]
},
{
"id": "10080948_E10",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
583,
590
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E11"
},
{
"role": "Cause",
"ref_id": "10080948_E9"
}
]
},
{
"id": "10080948_E11",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
624,
628
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T6"
},
{
"role": "Theme",
"ref_id": "10080948_T7"
}
]
},
{
"id": "10080948_E12",
"type": "Binding",
"trigger": {
"text": [
"interacted"
],
"offsets": [
[
704,
714
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T8"
},
{
"role": "Theme",
"ref_id": "10080948_T9"
},
{
"role": "Site",
"ref_id": "10080948_T29"
}
]
},
{
"id": "10080948_E13",
"type": "Phosphorylation",
"trigger": {
"text": [
"underphosphorylated"
],
"offsets": [
[
735,
754
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T9"
}
]
},
{
"id": "10080948_E14",
"type": "Negative_regulation",
"trigger": {
"text": [
"underphosphorylated"
],
"offsets": [
[
735,
754
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E13"
}
]
},
{
"id": "10080948_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
806,
814
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E16"
}
]
},
{
"id": "10080948_E16",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
819,
826
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T10"
},
{
"role": "Theme",
"ref_id": "10080948_T11"
}
]
},
{
"id": "10080948_E17",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
885,
900
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T12"
}
]
},
{
"id": "10080948_E18",
"type": "Regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
998,
1007
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_E19"
},
{
"role": "Cause",
"ref_id": "10080948_E17"
}
]
},
{
"id": "10080948_E19",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1023,
1034
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10080948_T13"
},
{
"role": "Theme",
"ref_id": "10080948_T14"
}
]
}
] | [] | [] |
8454603 | 8454603 | [
{
"id": "8454603__text",
"type": "abstract",
"text": [
"Transcriptional regulation of interleukin 3 (IL3) in primary human T lymphocytes. Role of AP-1- and octamer-binding proteins in control of IL3 gene expression. \nWe have investigated the molecular and biochemical basis for activation of interleukin 3 (IL3) gene expression in primary human T lymphocytes following CD3 and CD2 receptor stimulation or activation by phytohemagglutinin plus phorbol 12-myristate 13-acetate. Using transfection and reporter gene assays specifically designed for primary T lymphocytes in conjunction with gel retardation assays, Western blot analyses and UV cross-linking studies, we found that c-Jun, c-Fos, and octamer-binding proteins play a major role in transcriptional activation of the IL3 gene via their interaction with two specific regions contained within the IL3 5'-flanking sequence. Additionally, the region between bases -107 and -59 of the IL3 promoter containing putative AP-2 and Sp1 binding motifs appears necessary for basal level expression of the IL3 gene. The data also indicate that CD2 receptor activation and phytohemagglutinin plus phorbol 12-myristate 13-acetate stimulation augment T cell IL3 gene expression through the same cis- and trans-activating signals. These results should contribute to a better understanding of the regulation of IL3 gene expression in human T lymphocytes. "
],
"offsets": [
[
0,
1340
]
]
}
] | [
{
"id": "8454603_T1",
"type": "Protein",
"text": [
"interleukin 3"
],
"offsets": [
[
30,
43
]
],
"normalized": []
},
{
"id": "8454603_T2",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
45,
48
]
],
"normalized": []
},
{
"id": "8454603_T3",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
139,
142
]
],
"normalized": []
},
{
"id": "8454603_T4",
"type": "Protein",
"text": [
"interleukin 3"
],
"offsets": [
[
236,
249
]
],
"normalized": []
},
{
"id": "8454603_T5",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
251,
254
]
],
"normalized": []
},
{
"id": "8454603_T6",
"type": "Protein",
"text": [
"CD2"
],
"offsets": [
[
321,
324
]
],
"normalized": []
},
{
"id": "8454603_T7",
"type": "Protein",
"text": [
"phytohemagglutinin"
],
"offsets": [
[
363,
381
]
],
"normalized": []
},
{
"id": "8454603_T8",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
622,
627
]
],
"normalized": []
},
{
"id": "8454603_T9",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
629,
634
]
],
"normalized": []
},
{
"id": "8454603_T10",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
720,
723
]
],
"normalized": []
},
{
"id": "8454603_T11",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
798,
801
]
],
"normalized": []
},
{
"id": "8454603_T12",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
883,
886
]
],
"normalized": []
},
{
"id": "8454603_T13",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
925,
928
]
],
"normalized": []
},
{
"id": "8454603_T14",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
996,
999
]
],
"normalized": []
},
{
"id": "8454603_T15",
"type": "Protein",
"text": [
"CD2"
],
"offsets": [
[
1034,
1037
]
],
"normalized": []
},
{
"id": "8454603_T16",
"type": "Protein",
"text": [
"phytohemagglutinin"
],
"offsets": [
[
1062,
1080
]
],
"normalized": []
},
{
"id": "8454603_T17",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
1145,
1148
]
],
"normalized": []
},
{
"id": "8454603_T18",
"type": "Protein",
"text": [
"IL3"
],
"offsets": [
[
1296,
1299
]
],
"normalized": []
}
] | [
{
"id": "8454603_E1",
"type": "Transcription",
"trigger": {
"text": [
"Transcriptional"
],
"offsets": [
[
0,
15
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T2"
}
]
},
{
"id": "8454603_E2",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
16,
26
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E1"
}
]
},
{
"id": "8454603_E3",
"type": "Regulation",
"trigger": {
"text": [
"Role"
],
"offsets": [
[
82,
86
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E4"
}
]
},
{
"id": "8454603_E4",
"type": "Regulation",
"trigger": {
"text": [
"control"
],
"offsets": [
[
128,
135
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E5"
}
]
},
{
"id": "8454603_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
148,
158
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T3"
}
]
},
{
"id": "8454603_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
222,
232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E9"
},
{
"role": "Cause",
"ref_id": "8454603_E11"
}
]
},
{
"id": "8454603_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
222,
232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E9"
}
]
},
{
"id": "8454603_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
222,
232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E9"
},
{
"role": "Cause",
"ref_id": "8454603_E10"
}
]
},
{
"id": "8454603_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
261,
271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T5"
}
]
},
{
"id": "8454603_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
334,
345
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T6"
}
]
},
{
"id": "8454603_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
349,
359
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T7"
}
]
},
{
"id": "8454603_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"play a major role"
],
"offsets": [
[
665,
682
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E16"
}
]
},
{
"id": "8454603_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"play a major role"
],
"offsets": [
[
665,
682
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E16"
},
{
"role": "Cause",
"ref_id": "8454603_E18"
}
]
},
{
"id": "8454603_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"play a major role"
],
"offsets": [
[
665,
682
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E16"
},
{
"role": "Cause",
"ref_id": "8454603_E17"
}
]
},
{
"id": "8454603_E15",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional"
],
"offsets": [
[
686,
701
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T10"
}
]
},
{
"id": "8454603_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
702,
712
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E15"
}
]
},
{
"id": "8454603_E17",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
739,
750
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T9"
}
]
},
{
"id": "8454603_E18",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
739,
750
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T8"
}
]
},
{
"id": "8454603_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
"offsets": [
[
952,
961
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E20"
}
]
},
{
"id": "8454603_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
978,
988
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T14"
}
]
},
{
"id": "8454603_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1047,
1057
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T15"
}
]
},
{
"id": "8454603_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"augment"
],
"offsets": [
[
1130,
1137
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E23"
}
]
},
{
"id": "8454603_E23",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1154,
1164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T17"
}
]
},
{
"id": "8454603_E24",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1282,
1292
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_E25"
}
]
},
{
"id": "8454603_E25",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1305,
1315
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8454603_T18"
}
]
}
] | [
{
"id": "8454603_1",
"entity_ids": [
"8454603_T1",
"8454603_T2"
]
},
{
"id": "8454603_2",
"entity_ids": [
"8454603_T4",
"8454603_T5"
]
}
] | [] |
9852958 | 9852958 | [
{
"id": "9852958__text",
"type": "abstract",
"text": [
"Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family. \nHere we report the expression of a fork head domain protein in human T helper cells. We cloned and characterized a fork head cDNA from human T helper cell mRNA using differential display RT-PCR. The cDNA contains a 546-nucleotide (nt) open reading frame (ORF) that codes for the carboxyl-terminal 180 amino acids (aa) of the recently identified fkhrl1 gene. This ORF does not contain the characteristic DNA-binding domain found in members of the forkhead protein family. In-vitro transcription/translation of this cDNA expressed a protein of approximately 20 kDa. We have generated antibodies that specifically immunoprecipitated the in-vitro-translated 20-kDa protein. This antibody also recognizes in human T lymphocytes a 70-kDa protein corresponding in size to that predicted for the fkhrl1 gene product. The mRNA levels for fkhrl1 is elevated in T helper-induced lymphocytes in comparison to PHA-stimulated T lymphocytes. Further characterization of FKHRL1 and its related family members should shed light on the transcriptional mechanisms of this fork head gene subfamily and their role in T helper cell differentiation and regulation of cell growth. "
],
"offsets": [
[
0,
1277
]
]
}
] | [
{
"id": "9852958_T1",
"type": "Protein",
"text": [
"FKHRL1P2"
],
"offsets": [
[
21,
29
]
],
"normalized": []
},
{
"id": "9852958_T2",
"type": "Protein",
"text": [
"fkhrl1"
],
"offsets": [
[
465,
471
]
],
"normalized": []
},
{
"id": "9852958_T3",
"type": "Protein",
"text": [
"fkhrl1"
],
"offsets": [
[
908,
914
]
],
"normalized": []
},
{
"id": "9852958_T4",
"type": "Protein",
"text": [
"fkhrl1"
],
"offsets": [
[
949,
955
]
],
"normalized": []
},
{
"id": "9852958_T5",
"type": "Protein",
"text": [
"FKHRL1"
],
"offsets": [
[
1075,
1081
]
],
"normalized": []
}
] | [
{
"id": "9852958_E1",
"type": "Regulation",
"trigger": {
"text": [
"developmentally regulated"
],
"offsets": [
[
47,
72
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9852958_T1"
}
]
},
{
"id": "9852958_E2",
"type": "Binding",
"trigger": {
"text": [
"recognizes"
],
"offsets": [
[
809,
819
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9852958_T3"
}
]
},
{
"id": "9852958_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"product"
],
"offsets": [
[
920,
927
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9852958_T3"
}
]
},
{
"id": "9852958_E4",
"type": "Transcription",
"trigger": {
"text": [
"mRNA levels"
],
"offsets": [
[
933,
944
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9852958_T4"
}
]
},
{
"id": "9852958_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"elevated"
],
"offsets": [
[
959,
967
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9852958_E4"
}
]
}
] | [] | [] |
8852698 | 8852698 | [
{
"id": "8852698__text",
"type": "abstract",
"text": [
"Selenium-mediated inhibition of transcription factor NF-kappa B and HIV-1 LTR promoter activity. \nThe eukaryotic transcription factor NF-kappa B is involved in the inducible expression of various inflammatory genes as well as in HIV-1 replication. Activation of NF-kappa B is induced by prooxidants and several stimuli eliciting oxidative stress, such as cytokines, lipopolysaccharide, UV irradiation and other mediators. Various antioxidants inhibit NF-kappa B activation in response to these stimuli. In this study, we have investigated the effects of selenium, an integral component of glutathione peroxidase (GPX), on NF-kappa B activation. In selenium-deprived Jurkat and ESb-L T lymphocytes, supplementation of selenium led to a substantial increase of GPX activity. Analysis of DNA binding revealed that NF-kappa B activation in response to TNF was significantly inhibited under these conditions. Likewise, reporter gene assays using luciferase constructs driven by the HIV-1 long terminal repeat showed a dose-dependent inhibition of NF-kappa B controlled gene expression by selenium. The effects of selenium were specific for NF-kappa B, since the activity of the transcription factor AP-1 was not suppressed. These data suggest that selenium supplementation may be used to modulate the expression of NF-kappa B target genes and HIV-1. "
],
"offsets": [
[
0,
1345
]
]
}
] | [
{
"id": "8852698_T1",
"type": "Protein",
"text": [
"glutathione peroxidase"
],
"offsets": [
[
589,
611
]
],
"normalized": []
},
{
"id": "8852698_T2",
"type": "Protein",
"text": [
"GPX"
],
"offsets": [
[
613,
616
]
],
"normalized": []
},
{
"id": "8852698_T3",
"type": "Protein",
"text": [
"GPX"
],
"offsets": [
[
759,
762
]
],
"normalized": []
}
] | [
{
"id": "8852698_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
747,
755
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8852698_T3"
}
]
}
] | [
{
"id": "8852698_1",
"entity_ids": [
"8852698_T1",
"8852698_T2"
]
}
] | [] |
7609053 | 7609053 | [
{
"id": "7609053__text",
"type": "abstract",
"text": [
"The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells. \nHuman immunodeficiency virus type 2 (HIV-2), like HIV-1, causes AIDS and is associated with AIDS cases primarily in West Africa. HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease. Consistent with these differences, we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1. Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat, activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements: a single kappa B site, two purine-rich binding sites, PuB1 and PuB2, and a pets site. We have now identified a novel cis-acting element within the HIV-2 enhancer, immediately upstream of the kappa B site, designated peri-kappa B. This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus, and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines. This is the first description of an HIV-2 enhancer element which displays such monocyte specificity, and no comparable enhancer element has been clearly defined for HIV-1. While a nuclear factor(s) from both peripheral blood monocytes and T cells binds the peri-kappa B site, electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells, thus supporting the transfection data. Further, while specific constitutive binding to the peri-kappa B site is seen in monocytes, stimulation with phorbol esters induces additional, specific binding. Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis. "
],
"offsets": [
[
0,
2197
]
]
}
] | [] | [] | [] | [] |
8455611 | 8455611 | [
{
"id": "8455611__text",
"type": "abstract",
"text": [
"Transcriptional activation of human zeta 2 globin promoter by the alpha globin regulatory element (HS-40): functional role of specific nuclear factor-DNA complexes. \nWe studied the functional interaction between human embryonic zeta 2 globin promoter and the alpha globin regulatory element (HS-40) located 40 kb upstream of the zeta 2 globin gene. It was shown by transient expression assay that HS-40 behaved as an authentic enhancer for high-level zeta 2 globin promoter activity in K562 cells, an erythroid cell line of embryonic and/or fetal origin. Although sequences located between -559 and -88 of the zeta 2 globin gene were dispensable for its expression on enhancerless plasmids, they were required for the HS-40 enhancer-mediated activity of the zeta 2 globin promoter. Site-directed mutagenesis demonstrated that this HS-40 enhancer-zeta 2 globin promoter interaction is mediated by the two GATA-1 factor binding motifs located at -230 and -104, respectively. The functional domains of HS-40 were also mapped. Bal 31 deletion mapping data suggested that one GATA-1 motif, one GT motif, and two NF-E2/AP1 motifs together formed the functional core of HS-40 in the erythroid-specific activation of the zeta 2 globin promoter. Site-directed mutagenesis further demonstrated that the enhancer function of one of the two NF-E2/AP1 motifs of HS-40 is mediated through its binding to NF-E2 but not AP1 transcription factor. Finally, we did genomic footprinting of the HS-40 enhancer region in K562 cells, adult nucleated erythroblasts, and different nonerythroid cells. All sequence motifs within the functional core of HS-40, as mapped by transient expression analysis, appeared to bind a nuclear factor(s) in living K562 cells but not in nonerythroid cells. On the other hand, only one of the apparently nonfunctional sequence motifs was bound with factors in vivo. In comparison to K562, nucleated erythroblasts from adult human bone marrow exhibited a similar but nonidentical pattern of nuclear factor binding in vivo at the HS-40 region. These data suggest that transcriptional activation of human embryonic zeta 2 globin gene and the fetal/adult alpha globin genes is mediated by erythroid cell-specific and developmental stage-specific nuclear factor-DNA complexes which form at the enhancer (HS-40) and the globin promoters. "
],
"offsets": [
[
0,
2340
]
]
}
] | [
{
"id": "8455611_T1",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
36,
49
]
],
"normalized": []
},
{
"id": "8455611_T2",
"type": "Protein",
"text": [
"alpha globin"
],
"offsets": [
[
66,
78
]
],
"normalized": []
},
{
"id": "8455611_T3",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
228,
241
]
],
"normalized": []
},
{
"id": "8455611_T4",
"type": "Protein",
"text": [
"alpha globin"
],
"offsets": [
[
259,
271
]
],
"normalized": []
},
{
"id": "8455611_T5",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
329,
342
]
],
"normalized": []
},
{
"id": "8455611_T6",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
451,
464
]
],
"normalized": []
},
{
"id": "8455611_T7",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
610,
623
]
],
"normalized": []
},
{
"id": "8455611_T8",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
758,
771
]
],
"normalized": []
},
{
"id": "8455611_T9",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
846,
859
]
],
"normalized": []
},
{
"id": "8455611_T10",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
904,
910
]
],
"normalized": []
},
{
"id": "8455611_T11",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1071,
1077
]
],
"normalized": []
},
{
"id": "8455611_T12",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
1213,
1226
]
],
"normalized": []
},
{
"id": "8455611_T13",
"type": "Protein",
"text": [
"zeta 2 globin"
],
"offsets": [
[
2120,
2133
]
],
"normalized": []
},
{
"id": "8455611_T14",
"type": "Protein",
"text": [
"alpha globin"
],
"offsets": [
[
2159,
2171
]
],
"normalized": []
},
{
"id": "8455611_T16",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
50,
58
]
],
"normalized": []
},
{
"id": "8455611_T18",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
465,
473
]
],
"normalized": []
},
{
"id": "8455611_T24",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
772,
780
]
],
"normalized": []
},
{
"id": "8455611_T27",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1227,
1235
]
],
"normalized": []
}
] | [
{
"id": "8455611_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"Transcriptional activation"
],
"offsets": [
[
0,
26
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T1"
},
{
"role": "Site",
"ref_id": "8455611_T16"
}
]
},
{
"id": "8455611_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"behaved as an authentic enhancer"
],
"offsets": [
[
403,
435
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T6"
},
{
"role": "Site",
"ref_id": "8455611_T18"
}
]
},
{
"id": "8455611_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"dispensable"
],
"offsets": [
[
634,
645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E4"
}
]
},
{
"id": "8455611_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
654,
664
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T7"
}
]
},
{
"id": "8455611_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
701,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E6"
}
]
},
{
"id": "8455611_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
733,
741
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E7"
}
]
},
{
"id": "8455611_E7",
"type": "Regulation",
"trigger": {
"text": [
"activity"
],
"offsets": [
[
742,
750
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T8"
},
{
"role": "Site",
"ref_id": "8455611_T24"
}
]
},
{
"id": "8455611_E8",
"type": "Regulation",
"trigger": {
"text": [
"formed the functional core"
],
"offsets": [
[
1133,
1159
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E9"
}
]
},
{
"id": "8455611_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1195,
1205
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T12"
},
{
"role": "Site",
"ref_id": "8455611_T27"
}
]
},
{
"id": "8455611_E10",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional"
],
"offsets": [
[
2074,
2089
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T13"
}
]
},
{
"id": "8455611_E11",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional"
],
"offsets": [
[
2074,
2089
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_T14"
}
]
},
{
"id": "8455611_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
2090,
2100
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E10"
}
]
},
{
"id": "8455611_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
2090,
2100
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E11"
}
]
},
{
"id": "8455611_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
2181,
2189
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E12"
}
]
},
{
"id": "8455611_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
2181,
2189
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8455611_E13"
}
]
}
] | [] | [] |
7969177 | 7969177 | [
{
"id": "7969177__text",
"type": "abstract",
"text": [
"A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein. \nA novel DNA sequence element termed the J element involved in the regulated expression of class II major histocompatibility complex genes was recently described. To study this element and its role in class II gene regulation further, a cDNA library was screened with oligonucleotide probes containing both the S element and the nearby J element of the human DPA gene. Several DNA clones were obtained by this procedure, one of which, clone 18, is reported and characterized here. It encodes a protein predicted to contain 688 amino acid residues, including 11 zinc finger motifs of the C2H2 type in the C-terminal region, that are Kruppel-like in the conservation of the H/C link sequence connecting them. The 160 N-terminal amino acids in the nonfinger region of clone 18 are highly homologous with similar regions of several other human, mouse, and Drosophila sequences, defining a subfamily of Kruppel-like zinc finger proteins termed TAB (tramtrack [ttk]-associated box) here. One of the Drosophila sequences, ttk, is a developmental control gene, while a second does not contain a zinc finger region but encodes a structure important in oocyte development. An acidic activation domain is located between the N-terminal conserved region of clone 18 and its zinc fingers. This protein appears to require both the S and J elements, which are separated by 10 bp for optimal binding. Antisense cDNA to clone 18 inhibited the expression of a reporter construct containing the DPA promoter, indicating its functional importance in the expression of this class II gene. "
],
"offsets": [
[
0,
1756
]
]
}
] | [
{
"id": "7969177_T1",
"type": "Protein",
"text": [
"DPA"
],
"offsets": [
[
75,
78
]
],
"normalized": []
},
{
"id": "7969177_T2",
"type": "Protein",
"text": [
"DPA"
],
"offsets": [
[
547,
550
]
],
"normalized": []
},
{
"id": "7969177_T3",
"type": "Protein",
"text": [
"DPA"
],
"offsets": [
[
1664,
1667
]
],
"normalized": []
}
] | [
{
"id": "7969177_E1",
"type": "Regulation",
"trigger": {
"text": [
"regulates"
],
"offsets": [
[
14,
23
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7969177_T1"
}
]
},
{
"id": "7969177_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"importance"
],
"offsets": [
[
1704,
1714
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7969177_E3"
}
]
},
{
"id": "7969177_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1722,
1732
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7969177_T1"
}
]
}
] | [] | [] |
7843251 | 7843251 | [
{
"id": "7843251__text",
"type": "abstract",
"text": [
"Protein kinase C is not a downstream effector of p21ras in activated T cells. \nThe aim of this present study was to investigate the role of protein kinase C (PKC), downstream of p21ras, in activating interleukin-2 (IL-2) gene expression. It has been reported that PKC is an effector of p21ras in T cells. Data is presented, using the potent and selective PKC inhibitor Ro 31-8425 and transient expression of a constitutively active ras mutant, which clearly shows that PKC is not downstream of p21ras in the induction of NF-AT and AP-1 transcriptional activity and in the expression of IL-2 in human Jurkat T cells. Reporter gene experiments demonstrated that NF-kappa B transcriptional activity is not affected by expression of activated p21ras. The signaling pathways involving PKC activation, calcium mobilization and ras activation combine to provide the necessary components for production of IL-2 during T cell activation. "
],
"offsets": [
[
0,
929
]
]
}
] | [
{
"id": "7843251_T1",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
49,
55
]
],
"normalized": []
},
{
"id": "7843251_T2",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
178,
184
]
],
"normalized": []
},
{
"id": "7843251_T3",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
200,
213
]
],
"normalized": []
},
{
"id": "7843251_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
215,
219
]
],
"normalized": []
},
{
"id": "7843251_T5",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
286,
292
]
],
"normalized": []
},
{
"id": "7843251_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
586,
590
]
],
"normalized": []
},
{
"id": "7843251_T7",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
739,
745
]
],
"normalized": []
},
{
"id": "7843251_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
898,
902
]
],
"normalized": []
}
] | [
{
"id": "7843251_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activating"
],
"offsets": [
[
189,
199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7843251_E2"
}
]
},
{
"id": "7843251_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
226,
236
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7843251_T4"
}
]
},
{
"id": "7843251_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
572,
582
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7843251_T6"
}
]
},
{
"id": "7843251_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
729,
738
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7843251_T7"
}
]
},
{
"id": "7843251_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
884,
894
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7843251_T8"
}
]
},
{
"id": "7843251_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"during"
],
"offsets": [
[
903,
909
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7843251_E5"
}
]
}
] | [
{
"id": "7843251_1",
"entity_ids": [
"7843251_T3",
"7843251_T4"
]
}
] | [] |
9446322 | 9446322 | [
{
"id": "9446322__text",
"type": "abstract",
"text": [
"[Molecular-biologic aspects of interaction between nervous and immune systems] \nThe problem of the neuro-immuno interactions on the level of the protein trans-factors, stimulating interleukin-2 (IL-2) gene expression was discussed. The physico-chemical and functional parameters of the low molecular nuclear proteins (SP and BP- 14, 18, 19 kDs) isolated from splenic and brain cells of immunized rats were studied. The binding of these proteins to the regulatory region of IL-2 gene in vitro and stimulation of the IL-2mRNA synthesis in splenic T-lymphocytes culture in normal conditions were shown. The protective effect of SP and BP on the IL-2mRNA synthesis in stressful conditions and by the T-cells treatment with the CsA was demonstrated. "
],
"offsets": [
[
0,
745
]
]
}
] | [
{
"id": "9446322_T1",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
180,
193
]
],
"normalized": []
},
{
"id": "9446322_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
195,
199
]
],
"normalized": []
},
{
"id": "9446322_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
473,
477
]
],
"normalized": []
},
{
"id": "9446322_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
515,
519
]
],
"normalized": []
},
{
"id": "9446322_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
642,
646
]
],
"normalized": []
}
] | [
{
"id": "9446322_E1",
"type": "Regulation",
"trigger": {
"text": [
"stimulating"
],
"offsets": [
[
168,
179
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9446322_E2"
}
]
},
{
"id": "9446322_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"gene expression"
],
"offsets": [
[
201,
216
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9446322_T2"
}
]
},
{
"id": "9446322_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
496,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9446322_E4"
}
]
},
{
"id": "9446322_E4",
"type": "Transcription",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
524,
533
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9446322_T4"
}
]
},
{
"id": "9446322_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"protective effect"
],
"offsets": [
[
604,
621
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9446322_E6"
}
]
},
{
"id": "9446322_E6",
"type": "Transcription",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
651,
660
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9446322_T5"
}
]
}
] | [
{
"id": "9446322_1",
"entity_ids": [
"9446322_T1",
"9446322_T2"
]
}
] | [] |
9419430 | 9419430 | [
{
"id": "9419430__text",
"type": "abstract",
"text": [
"Agonistic activity of a CD40-specific single-chain Fv constructed from the variable regions of mAb G28-5. \nA single-chain Fv (sFv) was expressed from the variable regions of the CD40-specific mAb G28-5. The molecule bound CD40 with a high affinity (2.2 nM) and was a monomer in solution. Surprisingly, G28-5 sFv was a potent CD40 agonist that rapidly crosslinked CD40 on the cell surface but did not crosslink CD40-Ig in solution. G28-5 sFv was a more potent agonist than G28-5 IgG and was able to stimulate CD40 responses by B cells and monocytes. G28-5 IgG partially blocked, whereas G28-5 sFv augmented CD40 responses during stimulation with natural ligand (gp39-CD8 fusion protein). These results indicate that the functional activity of ligands built from the binding site of G28-5 is highly dependent upon the size and physical properties of the molecule both in solution and on the cell surfaces. "
],
"offsets": [
[
0,
904
]
]
}
] | [
{
"id": "9419430_T1",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
24,
28
]
],
"normalized": []
},
{
"id": "9419430_T2",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
178,
182
]
],
"normalized": []
},
{
"id": "9419430_T3",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
222,
226
]
],
"normalized": []
},
{
"id": "9419430_T4",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
325,
329
]
],
"normalized": []
},
{
"id": "9419430_T5",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
363,
367
]
],
"normalized": []
},
{
"id": "9419430_T6",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
410,
414
]
],
"normalized": []
},
{
"id": "9419430_T7",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
508,
512
]
],
"normalized": []
},
{
"id": "9419430_T8",
"type": "Protein",
"text": [
"IgG"
],
"offsets": [
[
555,
558
]
],
"normalized": []
},
{
"id": "9419430_T9",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
606,
610
]
],
"normalized": []
},
{
"id": "9419430_T10",
"type": "Protein",
"text": [
"gp39"
],
"offsets": [
[
661,
665
]
],
"normalized": []
}
] | [
{
"id": "9419430_E1",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
216,
221
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9419430_T3"
}
]
},
{
"id": "9419430_E2",
"type": "Binding",
"trigger": {
"text": [
"crosslinked"
],
"offsets": [
[
351,
362
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9419430_T5"
}
]
},
{
"id": "9419430_E3",
"type": "Binding",
"trigger": {
"text": [
"crosslink"
],
"offsets": [
[
400,
409
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9419430_T6"
}
]
}
] | [] | [] |
1939341 | 1939341 | [
{
"id": "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
]
]
}
] | [
{
"id": "1939341_T1",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
117,
122
]
],
"normalized": []
},
{
"id": "1939341_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
127,
132
]
],
"normalized": []
},
{
"id": "1939341_T3",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
345,
350
]
],
"normalized": []
},
{
"id": "1939341_T4",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
355,
360
]
],
"normalized": []
},
{
"id": "1939341_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
485,
490
]
],
"normalized": []
},
{
"id": "1939341_T6",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
495,
500
]
],
"normalized": []
},
{
"id": "1939341_T7",
"type": "Protein",
"text": [
"lamin A"
],
"offsets": [
[
673,
680
]
],
"normalized": []
},
{
"id": "1939341_T8",
"type": "Protein",
"text": [
"lamin C"
],
"offsets": [
[
682,
689
]
],
"normalized": []
},
{
"id": "1939341_T9",
"type": "Protein",
"text": [
"vimentin"
],
"offsets": [
[
695,
703
]
],
"normalized": []
},
{
"id": "1939341_T10",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
814,
819
]
],
"normalized": []
},
{
"id": "1939341_T11",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
824,
829
]
],
"normalized": []
},
{
"id": "1939341_T12",
"type": "Protein",
"text": [
"PKC"
],
"offsets": [
[
977,
980
]
],
"normalized": []
},
{
"id": "1939341_T13",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1128,
1133
]
],
"normalized": []
},
{
"id": "1939341_T14",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1138,
1143
]
],
"normalized": []
},
{
"id": "1939341_T15",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1236,
1241
]
],
"normalized": []
},
{
"id": "1939341_T16",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1246,
1251
]
],
"normalized": []
},
{
"id": "1939341_T17",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1496,
1501
]
],
"normalized": []
},
{
"id": "1939341_T18",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
1535,
1568
]
],
"normalized": []
},
{
"id": "1939341_T19",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1570,
1573
]
],
"normalized": []
},
{
"id": "1939341_T20",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1594,
1597
]
],
"normalized": []
},
{
"id": "1939341_T21",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1798,
1801
]
],
"normalized": []
},
{
"id": "1939341_T22",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1933,
1938
]
],
"normalized": []
}
] | [
{
"id": "1939341_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulation"
],
"offsets": [
[
98,
113
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T2"
}
]
},
{
"id": "1939341_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulation"
],
"offsets": [
[
98,
113
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T1"
}
]
},
{
"id": "1939341_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
451,
459
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E6"
}
]
},
{
"id": "1939341_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
451,
459
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E5"
}
]
},
{
"id": "1939341_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
472,
481
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T5"
}
]
},
{
"id": "1939341_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
472,
481
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T6"
}
]
},
{
"id": "1939341_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
634,
644
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E10"
}
]
},
{
"id": "1939341_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
634,
644
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E12"
}
]
},
{
"id": "1939341_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
634,
644
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E11"
}
]
},
{
"id": "1939341_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
660,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T7"
}
]
},
{
"id": "1939341_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
660,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T9"
}
]
},
{
"id": "1939341_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
660,
669
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T8"
}
]
},
{
"id": "1939341_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
796,
806
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T11"
}
]
},
{
"id": "1939341_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
796,
806
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T10"
}
]
},
{
"id": "1939341_E15",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
866,
875
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E14"
}
]
},
{
"id": "1939341_E16",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
866,
875
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E13"
}
]
},
{
"id": "1939341_E17",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
941,
947
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E18"
}
]
},
{
"id": "1939341_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
963,
973
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T12"
}
]
},
{
"id": "1939341_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1115,
1124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E22"
}
]
},
{
"id": "1939341_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1115,
1124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E21"
}
]
},
{
"id": "1939341_E21",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1144,
1154
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T14"
}
]
},
{
"id": "1939341_E22",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1144,
1154
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T13"
}
]
},
{
"id": "1939341_E23",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
1165,
1174
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E20"
}
]
},
{
"id": "1939341_E24",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
1165,
1174
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E19"
}
]
},
{
"id": "1939341_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1214,
1221
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E27"
}
]
},
{
"id": "1939341_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1214,
1221
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E28"
}
]
},
{
"id": "1939341_E27",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1222,
1232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T15"
}
]
},
{
"id": "1939341_E28",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1222,
1232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T16"
}
]
},
{
"id": "1939341_E29",
"type": "Positive_regulation",
"trigger": {
"text": [
"require"
],
"offsets": [
[
1261,
1268
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E25"
}
]
},
{
"id": "1939341_E30",
"type": "Positive_regulation",
"trigger": {
"text": [
"require"
],
"offsets": [
[
1261,
1268
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E26"
}
]
},
{
"id": "1939341_E31",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1300,
1307
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E36"
}
]
},
{
"id": "1939341_E32",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1300,
1307
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E35"
}
]
},
{
"id": "1939341_E33",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1336,
1345
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E32"
}
]
},
{
"id": "1939341_E34",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1336,
1345
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E31"
}
]
},
{
"id": "1939341_E35",
"type": "Transcription",
"trigger": {
"text": [
"at the transcriptional level"
],
"offsets": [
[
1346,
1374
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T14"
}
]
},
{
"id": "1939341_E36",
"type": "Transcription",
"trigger": {
"text": [
"at the transcriptional level"
],
"offsets": [
[
1346,
1374
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T13"
}
]
},
{
"id": "1939341_E37",
"type": "Positive_regulation",
"trigger": {
"text": [
"Increases"
],
"offsets": [
[
1581,
1590
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T20"
}
]
},
{
"id": "1939341_E38",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1785,
1794
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T21"
}
]
},
{
"id": "1939341_E39",
"type": "Regulation",
"trigger": {
"text": [
"sensitive"
],
"offsets": [
[
1815,
1824
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E38"
}
]
},
{
"id": "1939341_E40",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulates"
],
"offsets": [
[
1885,
1899
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E42"
}
]
},
{
"id": "1939341_E41",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1904,
1911
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_E42"
}
]
},
{
"id": "1939341_E42",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1912,
1925
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1939341_T22"
}
]
}
] | [
{
"id": "1939341_1",
"entity_ids": [
"1939341_T18",
"1939341_T19"
]
}
] | [] |
7594489 | 7594489 | [
{
"id": "7594489__text",
"type": "abstract",
"text": [
"Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells. \nMonocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time. Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro. The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat. The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells. Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS. We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors. The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors. Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex. "
],
"offsets": [
[
0,
2035
]
]
}
] | [
{
"id": "7594489_T1",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
35,
38
]
],
"normalized": []
},
{
"id": "7594489_T2",
"type": "Protein",
"text": [
"CD35"
],
"offsets": [
[
40,
44
]
],
"normalized": []
},
{
"id": "7594489_T3",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
55,
60
]
],
"normalized": []
},
{
"id": "7594489_T4",
"type": "Protein",
"text": [
"CD18"
],
"offsets": [
[
61,
65
]
],
"normalized": []
},
{
"id": "7594489_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
112,
115
]
],
"normalized": []
},
{
"id": "7594489_T6",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
116,
119
]
],
"normalized": []
},
{
"id": "7594489_T7",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
398,
407
]
],
"normalized": []
},
{
"id": "7594489_T8",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
440,
449
]
],
"normalized": []
},
{
"id": "7594489_T9",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
554,
557
]
],
"normalized": []
},
{
"id": "7594489_T10",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
558,
561
]
],
"normalized": []
},
{
"id": "7594489_T11",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
703,
706
]
],
"normalized": []
},
{
"id": "7594489_T12",
"type": "Protein",
"text": [
"CD35"
],
"offsets": [
[
708,
712
]
],
"normalized": []
},
{
"id": "7594489_T13",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
723,
728
]
],
"normalized": []
},
{
"id": "7594489_T14",
"type": "Protein",
"text": [
"CD18"
],
"offsets": [
[
729,
733
]
],
"normalized": []
},
{
"id": "7594489_T15",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
974,
977
]
],
"normalized": []
},
{
"id": "7594489_T16",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
1031,
1034
]
],
"normalized": []
},
{
"id": "7594489_T17",
"type": "Protein",
"text": [
"p24"
],
"offsets": [
[
1124,
1127
]
],
"normalized": []
},
{
"id": "7594489_T18",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
1265,
1268
]
],
"normalized": []
},
{
"id": "7594489_T19",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1324,
1327
]
],
"normalized": []
},
{
"id": "7594489_T20",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1328,
1331
]
],
"normalized": []
},
{
"id": "7594489_T21",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1379,
1382
]
],
"normalized": []
},
{
"id": "7594489_T22",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1383,
1386
]
],
"normalized": []
},
{
"id": "7594489_T23",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
1430,
1433
]
],
"normalized": []
},
{
"id": "7594489_T24",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1621,
1630
]
],
"normalized": []
},
{
"id": "7594489_T25",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1679,
1682
]
],
"normalized": []
},
{
"id": "7594489_T26",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1683,
1686
]
],
"normalized": []
},
{
"id": "7594489_T29",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
75,
82
]
],
"normalized": []
},
{
"id": "7594489_T32",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
489,
496
]
],
"normalized": []
},
{
"id": "7594489_T40",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
1288,
1295
]
],
"normalized": []
}
] | [
{
"id": "7594489_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"Triggering"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T2"
}
]
},
{
"id": "7594489_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"Triggering"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T3"
}
]
},
{
"id": "7594489_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"Triggering"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T4"
}
]
},
{
"id": "7594489_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
67,
74
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E10"
},
{
"role": "Cause",
"ref_id": "7594489_E2"
}
]
},
{
"id": "7594489_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
67,
74
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E10"
},
{
"role": "Cause",
"ref_id": "7594489_E3"
}
]
},
{
"id": "7594489_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
67,
74
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E11"
},
{
"role": "Cause",
"ref_id": "7594489_E1"
}
]
},
{
"id": "7594489_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
67,
74
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E10"
},
{
"role": "Cause",
"ref_id": "7594489_E1"
}
]
},
{
"id": "7594489_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
67,
74
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E11"
},
{
"role": "Cause",
"ref_id": "7594489_E3"
}
]
},
{
"id": "7594489_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
67,
74
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E11"
},
{
"role": "Cause",
"ref_id": "7594489_E2"
}
]
},
{
"id": "7594489_E10",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
83,
96
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T6"
},
{
"role": "ToLoc",
"ref_id": "7594489_T29"
}
]
},
{
"id": "7594489_E11",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
83,
96
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T5"
},
{
"role": "ToLoc",
"ref_id": "7594489_T29"
}
]
},
{
"id": "7594489_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
482,
488
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E16"
}
]
},
{
"id": "7594489_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
482,
488
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E17"
}
]
},
{
"id": "7594489_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
482,
488
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E17"
},
{
"role": "Cause",
"ref_id": "7594489_T8"
}
]
},
{
"id": "7594489_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
482,
488
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E16"
},
{
"role": "Cause",
"ref_id": "7594489_T8"
}
]
},
{
"id": "7594489_E16",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
497,
510
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T9"
},
{
"role": "ToLoc",
"ref_id": "7594489_T32"
}
]
},
{
"id": "7594489_E17",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
497,
510
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T10"
},
{
"role": "ToLoc",
"ref_id": "7594489_T32"
}
]
},
{
"id": "7594489_E18",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
570,
575
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T10"
}
]
},
{
"id": "7594489_E19",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
570,
575
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T9"
}
]
},
{
"id": "7594489_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"triggering"
],
"offsets": [
[
668,
678
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T12"
}
]
},
{
"id": "7594489_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"triggering"
],
"offsets": [
[
668,
678
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T13"
}
]
},
{
"id": "7594489_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"triggering"
],
"offsets": [
[
668,
678
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T14"
}
]
},
{
"id": "7594489_E23",
"type": "Positive_regulation",
"trigger": {
"text": [
"Stimulation"
],
"offsets": [
[
1016,
1027
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T16"
}
]
},
{
"id": "7594489_E24",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1069,
1077
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T17"
}
]
},
{
"id": "7594489_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1069,
1077
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T17"
},
{
"role": "Cause",
"ref_id": "7594489_E23"
}
]
},
{
"id": "7594489_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1250,
1261
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T18"
}
]
},
{
"id": "7594489_E27",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1276,
1283
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E32"
}
]
},
{
"id": "7594489_E28",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1276,
1283
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E31"
},
{
"role": "Cause",
"ref_id": "7594489_E26"
}
]
},
{
"id": "7594489_E29",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1276,
1283
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E31"
}
]
},
{
"id": "7594489_E30",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
1276,
1283
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E32"
},
{
"role": "Cause",
"ref_id": "7594489_E26"
}
]
},
{
"id": "7594489_E31",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1296,
1309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T20"
},
{
"role": "ToLoc",
"ref_id": "7594489_T40"
}
]
},
{
"id": "7594489_E32",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1296,
1309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T19"
},
{
"role": "ToLoc",
"ref_id": "7594489_T40"
}
]
},
{
"id": "7594489_E33",
"type": "Localization",
"trigger": {
"text": [
"Translocation"
],
"offsets": [
[
1351,
1364
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T21"
}
]
},
{
"id": "7594489_E34",
"type": "Localization",
"trigger": {
"text": [
"Translocation"
],
"offsets": [
[
1351,
1364
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T22"
}
]
},
{
"id": "7594489_E35",
"type": "Positive_regulation",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1396,
1404
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E34"
},
{
"role": "Cause",
"ref_id": "7594489_E39"
}
]
},
{
"id": "7594489_E36",
"type": "Positive_regulation",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1396,
1404
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E33"
},
{
"role": "Cause",
"ref_id": "7594489_E39"
}
]
},
{
"id": "7594489_E37",
"type": "Positive_regulation",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1396,
1404
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E33"
}
]
},
{
"id": "7594489_E38",
"type": "Positive_regulation",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1396,
1404
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E34"
}
]
},
{
"id": "7594489_E39",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1415,
1426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T23"
}
]
},
{
"id": "7594489_E40",
"type": "Localization",
"trigger": {
"text": [
"translocated"
],
"offsets": [
[
1534,
1546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T21"
}
]
},
{
"id": "7594489_E41",
"type": "Localization",
"trigger": {
"text": [
"translocated"
],
"offsets": [
[
1534,
1546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T22"
}
]
},
{
"id": "7594489_E42",
"type": "Positive_regulation",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1567,
1575
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E40"
}
]
},
{
"id": "7594489_E43",
"type": "Positive_regulation",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1567,
1575
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E41"
}
]
},
{
"id": "7594489_E44",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediate"
],
"offsets": [
[
1639,
1646
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E49"
},
{
"role": "Cause",
"ref_id": "7594489_T24"
}
]
},
{
"id": "7594489_E45",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediate"
],
"offsets": [
[
1639,
1646
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_E48"
},
{
"role": "Cause",
"ref_id": "7594489_T24"
}
]
},
{
"id": "7594489_E46",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1651,
1664
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T25"
}
]
},
{
"id": "7594489_E47",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
1651,
1664
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T26"
}
]
},
{
"id": "7594489_E48",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1687,
1694
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T25"
}
]
},
{
"id": "7594489_E49",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1687,
1694
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594489_T26"
}
]
}
] | [
{
"id": "7594489_1",
"entity_ids": [
"7594489_T1",
"7594489_T2"
]
},
{
"id": "7594489_2",
"entity_ids": [
"7594489_T11",
"7594489_T12"
]
}
] | [] |
9731208 | 9731208 | [
{
"id": "9731208__text",
"type": "abstract",
"text": [
"An allosteric drug, o,o'-bismyristoyl thiamine disulfide, suppresses HIV-1 replication through prevention of nuclear translocation of both HIV-1 Tat and NF-kappa B. \nThe efficacy of o,o'-bismyristoyl thiamine disulfide (BMT) was examined in detail against HIV-1 laboratory isolates (HTLV-IIIB, JRFL, and MN), primary isolates (KMT and KMO), and simian immunodeficiency virus (SIVmac251) in vitro. BMT inhibited the replication of HIV-1 in both laboratory and primary isolates in vitro. In addition, BMT exhibited antiviral activity against SIVmac251. Minimizing energy studies of BMT structure reveal that a trans-disulfide of thiamine (holo drug) disulfide (TDS, protodrug) is allosterically transited to the reactive twisted disulfide of BMT (allo drug) by o,o'-bismyristoyl esterification of TDS. BMT inhibits nuclear translocation of both HIV-1 transactivator (TAT) and the cellular transcriptional nuclear factor-KB (NF-kappa B), resulting in the suppression of HIV-1 replication. "
],
"offsets": [
[
0,
986
]
]
}
] | [
{
"id": "9731208_T1",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
145,
148
]
],
"normalized": []
},
{
"id": "9731208_T2",
"type": "Protein",
"text": [
"TAT"
],
"offsets": [
[
865,
868
]
],
"normalized": []
},
{
"id": "9731208_T4",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
109,
116
]
],
"normalized": []
},
{
"id": "9731208_T7",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
813,
820
]
],
"normalized": []
}
] | [
{
"id": "9731208_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"prevention"
],
"offsets": [
[
95,
105
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9731208_E2"
}
]
},
{
"id": "9731208_E2",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
117,
130
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9731208_T1"
},
{
"role": "ToLoc",
"ref_id": "9731208_T4"
}
]
},
{
"id": "9731208_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
804,
812
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9731208_E4"
}
]
},
{
"id": "9731208_E4",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
821,
834
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9731208_T2"
},
{
"role": "ToLoc",
"ref_id": "9731208_T7"
}
]
}
] | [] | [] |
8557975 | 8557975 | [
{
"id": "8557975__text",
"type": "abstract",
"text": [
"MEK1 and the extracellular signal-regulated kinases are required for the stimulation of IL-2 gene transcription in T cells. \nTCR engagement stimulates the activation of the protein kinase Raf-1. Active Raf-1 phosphorylates and activates the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase 1 (MEK1), which in turn phosphorylates and activates the MAP kinases/extracellular signal regulated kinases, ERK1 and ERK2. Raf-1 activity promotes IL-2 production in activated T lymphocytes. Therefore, we sought to determine whether MEK1 and ERK activities also stimulate IL-2 gene transcription. Expression of constitutively active Raf-1 or MEK1 in Jurkat T cells enhanced the stimulation of IL-2 promoter-driven transcription stimulated by a calcium ionophore and PMA, and together with a calcium ionophore the expression of each protein was sufficient to stimulate NF-AT activity. Expression of MEK1-interfering mutants inhibited the stimulation of IL-2 promoter-driven transcription and blocked the ability of constitutively active Ras and Raf-1 to costimulate NF-AT activity with a calcium ionophore. Expression of the MAP kinase-specific phosphatase, MKP-1, which blocks ERK activation, inhibited IL-2 promoter and NF-AT-driven transcription stimulated by a calcium ionophore and PMA, and in addition, MKP-1 neutralized the transcriptional enhancement caused by active Raf-1 and MEK1 expression. We conclude that the MAP kinase signal transduction pathway consisting of Raf-1, MEK1, and ERK1 and ERK2 functions in the stimulation IL-2 gene transcription in activated T lymphocytes. "
],
"offsets": [
[
0,
1614
]
]
}
] | [
{
"id": "8557975_T1",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "8557975_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
88,
92
]
],
"normalized": []
},
{
"id": "8557975_T3",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
188,
193
]
],
"normalized": []
},
{
"id": "8557975_T4",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
202,
207
]
],
"normalized": []
},
{
"id": "8557975_T5",
"type": "Protein",
"text": [
"mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase 1"
],
"offsets": [
[
241,
326
]
],
"normalized": []
},
{
"id": "8557975_T6",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
328,
332
]
],
"normalized": []
},
{
"id": "8557975_T7",
"type": "Protein",
"text": [
"ERK1"
],
"offsets": [
[
434,
438
]
],
"normalized": []
},
{
"id": "8557975_T8",
"type": "Protein",
"text": [
"ERK2"
],
"offsets": [
[
443,
447
]
],
"normalized": []
},
{
"id": "8557975_T9",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
449,
454
]
],
"normalized": []
},
{
"id": "8557975_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
473,
477
]
],
"normalized": []
},
{
"id": "8557975_T11",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
559,
563
]
],
"normalized": []
},
{
"id": "8557975_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
598,
602
]
],
"normalized": []
},
{
"id": "8557975_T13",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
659,
664
]
],
"normalized": []
},
{
"id": "8557975_T14",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
668,
672
]
],
"normalized": []
},
{
"id": "8557975_T15",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
719,
723
]
],
"normalized": []
},
{
"id": "8557975_T16",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
924,
928
]
],
"normalized": []
},
{
"id": "8557975_T17",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
978,
982
]
],
"normalized": []
},
{
"id": "8557975_T18",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
1070,
1075
]
],
"normalized": []
},
{
"id": "8557975_T19",
"type": "Protein",
"text": [
"MKP-1"
],
"offsets": [
[
1183,
1188
]
],
"normalized": []
},
{
"id": "8557975_T20",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1229,
1233
]
],
"normalized": []
},
{
"id": "8557975_T21",
"type": "Protein",
"text": [
"MKP-1"
],
"offsets": [
[
1334,
1339
]
],
"normalized": []
},
{
"id": "8557975_T22",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
1401,
1406
]
],
"normalized": []
},
{
"id": "8557975_T23",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
1411,
1415
]
],
"normalized": []
},
{
"id": "8557975_T24",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
1502,
1507
]
],
"normalized": []
},
{
"id": "8557975_T25",
"type": "Protein",
"text": [
"MEK1"
],
"offsets": [
[
1509,
1513
]
],
"normalized": []
},
{
"id": "8557975_T26",
"type": "Protein",
"text": [
"ERK1"
],
"offsets": [
[
1519,
1523
]
],
"normalized": []
},
{
"id": "8557975_T27",
"type": "Protein",
"text": [
"ERK2"
],
"offsets": [
[
1528,
1532
]
],
"normalized": []
},
{
"id": "8557975_T28",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1562,
1566
]
],
"normalized": []
}
] | [
{
"id": "8557975_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
56,
64
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E3"
},
{
"role": "Cause",
"ref_id": "8557975_T1"
}
]
},
{
"id": "8557975_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
56,
64
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E3"
}
]
},
{
"id": "8557975_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
73,
84
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E4"
}
]
},
{
"id": "8557975_E4",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
98,
111
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T2"
}
]
},
{
"id": "8557975_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulates the activation"
],
"offsets": [
[
140,
165
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T3"
}
]
},
{
"id": "8557975_E6",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
208,
222
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T6"
}
]
},
{
"id": "8557975_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
208,
222
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E6"
},
{
"role": "Cause",
"ref_id": "8557975_T4"
}
]
},
{
"id": "8557975_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
227,
236
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T6"
},
{
"role": "Cause",
"ref_id": "8557975_T4"
}
]
},
{
"id": "8557975_E9",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
349,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T7"
}
]
},
{
"id": "8557975_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
349,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E9"
},
{
"role": "Cause",
"ref_id": "8557975_T6"
}
]
},
{
"id": "8557975_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
349,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E12"
},
{
"role": "Cause",
"ref_id": "8557975_T6"
}
]
},
{
"id": "8557975_E12",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
349,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T8"
}
]
},
{
"id": "8557975_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
368,
377
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T7"
},
{
"role": "Cause",
"ref_id": "8557975_T6"
}
]
},
{
"id": "8557975_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
368,
377
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T8"
},
{
"role": "Cause",
"ref_id": "8557975_T6"
}
]
},
{
"id": "8557975_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"promotes"
],
"offsets": [
[
464,
472
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E16"
},
{
"role": "Cause",
"ref_id": "8557975_T9"
}
]
},
{
"id": "8557975_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
478,
488
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T10"
}
]
},
{
"id": "8557975_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
588,
597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E19"
}
]
},
{
"id": "8557975_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
588,
597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E19"
},
{
"role": "Cause",
"ref_id": "8557975_T11"
}
]
},
{
"id": "8557975_E19",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
608,
621
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T12"
}
]
},
{
"id": "8557975_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"Expression"
],
"offsets": [
[
623,
633
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T13"
}
]
},
{
"id": "8557975_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"Expression"
],
"offsets": [
[
623,
633
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T14"
}
]
},
{
"id": "8557975_E22",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
839,
849
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T14"
}
]
},
{
"id": "8557975_E23",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
839,
849
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T13"
}
]
},
{
"id": "8557975_E24",
"type": "Gene_expression",
"trigger": {
"text": [
"Expression"
],
"offsets": [
[
1132,
1142
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T19"
}
]
},
{
"id": "8557975_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1416,
1426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T23"
}
]
},
{
"id": "8557975_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1416,
1426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T22"
}
]
},
{
"id": "8557975_E27",
"type": "Regulation",
"trigger": {
"text": [
"functions"
],
"offsets": [
[
1533,
1542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E32"
},
{
"role": "Cause",
"ref_id": "8557975_T26"
}
]
},
{
"id": "8557975_E28",
"type": "Regulation",
"trigger": {
"text": [
"functions"
],
"offsets": [
[
1533,
1542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E32"
},
{
"role": "Cause",
"ref_id": "8557975_T27"
}
]
},
{
"id": "8557975_E29",
"type": "Regulation",
"trigger": {
"text": [
"functions"
],
"offsets": [
[
1533,
1542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E32"
}
]
},
{
"id": "8557975_E30",
"type": "Regulation",
"trigger": {
"text": [
"functions"
],
"offsets": [
[
1533,
1542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E32"
},
{
"role": "Cause",
"ref_id": "8557975_T24"
}
]
},
{
"id": "8557975_E31",
"type": "Regulation",
"trigger": {
"text": [
"functions"
],
"offsets": [
[
1533,
1542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E32"
},
{
"role": "Cause",
"ref_id": "8557975_T25"
}
]
},
{
"id": "8557975_E32",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1550,
1561
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_E33"
}
]
},
{
"id": "8557975_E33",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1572,
1585
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8557975_T28"
}
]
}
] | [
{
"id": "8557975_1",
"entity_ids": [
"8557975_T5",
"8557975_T6"
]
}
] | [] |
8632999 | 8632999 | [
{
"id": "8632999__text",
"type": "abstract",
"text": [
"CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency. \nTumor necrosis factor (TNF) mediates a wide variety of disease states including septic shock, acute and chronic inflammation, and cachexia. Recently, a multivalent guanylhydrazone (CNI-1493) developed as an inhibitor of macrophage activation was shown to suppress TNF production and protect against tissue inflammation and endotoxin lethality [Bianchi, M., Ulrich, P., Bloom, O., Meistrell, M., Zimmerman, G.A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., Sherry, B., Manogue, K.R., Tortolani, A.J., Cerami, A.& Tracey, K.J.(1995) Mol.Med.1, 254-266, and Bianchi, M., Bloom, O., Raabe, T., Cohen, P. S., Chesney, J., Sherry, B., Schmidtmayerova, H., Zhang, X., Bukrinsky, M., Ulrich, P., Cerami, A.& Tracey, J.(1996) J.Exp.Med., in press]. We have now elucidated the mechanism by which CNI-1493 inhibits macrophage TNF synthesis and show here that it acts through suppression of TNF translation efficiency. CNI-1493 blocked neither the lipopolysaccharide (LPS)-induced increases in the expression of TNF mRNA nor the translocation of nuclear factor NF-kappa B to the nucleus in macrophages activated by 15 min of LPS stimulation, indicating that CNI-1493 does not interfere with early NF-kappa B-mediated transcriptional regulation of TNF. However, synthesis of the 26-kDa membrane form of TNF was effectively blocked by CNI-1493. Further evidence for the translational suppression of TNF is given by experiments using chloram-phenicol acetyltransferase (CAT) constructs containing elements of the TNF gene that are involved in TNF translational regulation. Both the 5' and 3' untranslated regions of the TNF gene were required to elicit maximal translational suppression by CNI-1493. Identification of the molecular target through which CNI- 1493 inhibits TNF translation should provide insight into the regulation of macrophage activation and mechanisms of inflammation. "
],
"offsets": [
[
0,
1995
]
]
}
] | [
{
"id": "8632999_T1",
"type": "Protein",
"text": [
"chloram-phenicol acetyltransferase"
],
"offsets": [
[
1541,
1575
]
],
"normalized": []
},
{
"id": "8632999_T2",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1577,
1580
]
],
"normalized": []
}
] | [] | [
{
"id": "8632999_1",
"entity_ids": [
"8632999_T1",
"8632999_T2"
]
}
] | [] |
9310836 | 9310836 | [
{
"id": "9310836__text",
"type": "abstract",
"text": [
"Four P-like elements are required for optimal transcription of the mouse IL-4 gene: involvement of a distinct set of nuclear factor of activated T cells and activator protein-1 family proteins. \nWe previously identified the P sequence as a critical regulatory element of the human IL-4 promoter. In the mouse IL-4 promoter, there are five elements homologous to the human P sequence designated conserved lymphokine element 0 (CLE0), P, P2, P3 and P4. To characterize the role of these P-like elements and their binding factors in the native promoter, we did transient transfection and electrophoretic mobility shift assays (EMSA). Transfection of EL-4 cells with the IL-4 promoter-reporter constructs carrying mutated P-like elements showed that four P-like elements, CLE0, P, P2 and P4, but not P3, were required for optimal activation of the IL-4 promoter. EMSA showed that both constitutive and inducible complexes bound to CLE0, P, P2 and P4, whereas only a constitutive complex bound to P3. In competition and antibody supershift assays in EMSA, complexes formed with P or P2 proved to contain nuclear factor of activated T cells (NFAT) family proteins as major components. Activator protein (AP)-1 family proteins interacted with CLE0, P, P2 and P4. NFAT/AP-1 complex formed only with P and P2. Cross-competition assays among the P-like elements revealed element-specific and common complexes. Six tandem repeats of the P element linked to the SV40 promoter responded to phorbol 12-myristate 13-acetate, while that of other elements did not. It would thus appear that components of each P-like element-binding complexes are not identical and may coordinately contribute to transcriptional activity. "
],
"offsets": [
[
0,
1705
]
]
}
] | [
{
"id": "9310836_T1",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
73,
77
]
],
"normalized": []
},
{
"id": "9310836_T2",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
281,
285
]
],
"normalized": []
},
{
"id": "9310836_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
309,
313
]
],
"normalized": []
},
{
"id": "9310836_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
667,
671
]
],
"normalized": []
},
{
"id": "9310836_T5",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
844,
848
]
],
"normalized": []
},
{
"id": "9310836_T9",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
849,
857
]
],
"normalized": []
}
] | [
{
"id": "9310836_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
25,
33
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9310836_E2"
}
]
},
{
"id": "9310836_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
46,
59
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9310836_T1"
}
]
},
{
"id": "9310836_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
826,
836
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9310836_T5"
},
{
"role": "Site",
"ref_id": "9310836_T9"
}
]
}
] | [] | [] |
8641353 | 8641353 | [
{
"id": "8641353__text",
"type": "abstract",
"text": [
"Expression of c-fos and c-jun proteins and AP-1 binding activity during cell cycle progression of HL60 cells and phytohemagglutinin-stimulated lymphocytes. \nThe protein products of the c-fos (p62c-fos) and c-jun (p39c-jun) genes are members of the AP-1 transcription factor family and are thought to play important roles in the regulation of gene expression during the cell cycle. Most studies on the expression of these proteins in relation to the cell cycle have been performed at the mRNA level, and therefore do not give direct information about the presence of the proteins during the cell cycle. We have used Western blotting to investigate the presence of these proteins during the cell cycles of two different cellular systems: a continuously growing myeloid leukemic cell line, HL60, and normal cells stimulated into cycle, phyto- hemagglutinin (PHA)-stimulated normal human peripheral blood lymphocytes (PBL). The binding activity of transcription factor AP-1, which consists of dimers of Fos and Jun family proteins, was also studied using a gel shift assay. We found nuclear p62c-fos, p39c-jun, and AP-1 binding activity throughout the cell cycle both in HL60 cells and in PHA-stimulated PBL, and we postulate that these proteins are required throughout the cell cycle and not transiently in the G0 to G1 transition as previous mRNA studies have indicated. We demonstrated an uncoupling of AP-1 binding activity from p62c-fos, and p39c-jun AP-1 activity was expressed more strongly in the G1- and G2/M-phase enriched samples than in the S-phase enriched samples of HL60 cells, while levels of nuclear p62c-fos and p39c-jun were constant. Nuclei of unstimulated PBL from different donors expressed p62c-fos and p39c-jun, but AP-1 was not detected in the majority of samples. Following PHA stimulation of PBL, the increase in AP-1 activity was delayed with respect to the augmentation of p39c-jun expression. We also observed that cytoplasmic p62c-fos and p39c-jun were present in HL60 cells and PHA-stimulated PBL. However, no cytoplasmic p62c-fos was detected in unstimulated PBL, although in some cases cytoplasmic p39c-jun was detected, suggesting that subcellular compartmentalization of these proteinsmay occur under certain circumstances. "
],
"offsets": [
[
0,
2256
]
]
}
] | [
{
"id": "8641353_T1",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
14,
19
]
],
"normalized": []
},
{
"id": "8641353_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
24,
29
]
],
"normalized": []
},
{
"id": "8641353_T3",
"type": "Protein",
"text": [
"phytohemagglutinin"
],
"offsets": [
[
113,
131
]
],
"normalized": []
},
{
"id": "8641353_T4",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
185,
190
]
],
"normalized": []
},
{
"id": "8641353_T5",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
192,
200
]
],
"normalized": []
},
{
"id": "8641353_T6",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
206,
211
]
],
"normalized": []
},
{
"id": "8641353_T7",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
213,
221
]
],
"normalized": []
},
{
"id": "8641353_T8",
"type": "Protein",
"text": [
"phyto- hemagglutinin"
],
"offsets": [
[
833,
853
]
],
"normalized": []
},
{
"id": "8641353_T9",
"type": "Protein",
"text": [
"PHA"
],
"offsets": [
[
855,
858
]
],
"normalized": []
},
{
"id": "8641353_T10",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
1087,
1095
]
],
"normalized": []
},
{
"id": "8641353_T11",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
1097,
1105
]
],
"normalized": []
},
{
"id": "8641353_T12",
"type": "Protein",
"text": [
"PHA"
],
"offsets": [
[
1185,
1188
]
],
"normalized": []
},
{
"id": "8641353_T13",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
1429,
1437
]
],
"normalized": []
},
{
"id": "8641353_T14",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
1443,
1451
]
],
"normalized": []
},
{
"id": "8641353_T15",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
1613,
1621
]
],
"normalized": []
},
{
"id": "8641353_T16",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
1626,
1634
]
],
"normalized": []
},
{
"id": "8641353_T17",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
1709,
1717
]
],
"normalized": []
},
{
"id": "8641353_T18",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
1722,
1730
]
],
"normalized": []
},
{
"id": "8641353_T19",
"type": "Protein",
"text": [
"PHA"
],
"offsets": [
[
1796,
1799
]
],
"normalized": []
},
{
"id": "8641353_T20",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
1898,
1906
]
],
"normalized": []
},
{
"id": "8641353_T21",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
1953,
1961
]
],
"normalized": []
},
{
"id": "8641353_T22",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
1966,
1974
]
],
"normalized": []
},
{
"id": "8641353_T23",
"type": "Protein",
"text": [
"PHA"
],
"offsets": [
[
2006,
2009
]
],
"normalized": []
},
{
"id": "8641353_T24",
"type": "Protein",
"text": [
"p62c-fos"
],
"offsets": [
[
2050,
2058
]
],
"normalized": []
},
{
"id": "8641353_T25",
"type": "Protein",
"text": [
"p39c-jun"
],
"offsets": [
[
2128,
2136
]
],
"normalized": []
},
{
"id": "8641353_T31",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
1079,
1086
]
],
"normalized": []
},
{
"id": "8641353_T33",
"type": "Entity",
"text": [
"Nuclei"
],
"offsets": [
[
1650,
1656
]
],
"normalized": []
}
] | [
{
"id": "8641353_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"Expression"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T2"
}
]
},
{
"id": "8641353_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"Expression"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T1"
}
]
},
{
"id": "8641353_E3",
"type": "Transcription",
"trigger": {
"text": [
"at the mRNA level"
],
"offsets": [
[
480,
497
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T5"
}
]
},
{
"id": "8641353_E4",
"type": "Transcription",
"trigger": {
"text": [
"at the mRNA level"
],
"offsets": [
[
480,
497
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T7"
}
]
},
{
"id": "8641353_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"presence"
],
"offsets": [
[
554,
562
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T7"
}
]
},
{
"id": "8641353_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"presence"
],
"offsets": [
[
554,
562
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T5"
}
]
},
{
"id": "8641353_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"presence"
],
"offsets": [
[
651,
659
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T5"
}
]
},
{
"id": "8641353_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"presence"
],
"offsets": [
[
651,
659
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T7"
}
]
},
{
"id": "8641353_E9",
"type": "Localization",
"trigger": {
"text": [
"found"
],
"offsets": [
[
1073,
1078
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T10"
},
{
"role": "AtLoc",
"ref_id": "8641353_T31"
}
]
},
{
"id": "8641353_E10",
"type": "Localization",
"trigger": {
"text": [
"found"
],
"offsets": [
[
1073,
1078
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T11"
},
{
"role": "AtLoc",
"ref_id": "8641353_T31"
}
]
},
{
"id": "8641353_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"constant"
],
"offsets": [
[
1640,
1648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T16"
}
]
},
{
"id": "8641353_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"constant"
],
"offsets": [
[
1640,
1648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T15"
}
]
},
{
"id": "8641353_E13",
"type": "Localization",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
1699,
1708
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T17"
},
{
"role": "AtLoc",
"ref_id": "8641353_T33"
}
]
},
{
"id": "8641353_E14",
"type": "Localization",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
1699,
1708
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T18"
},
{
"role": "AtLoc",
"ref_id": "8641353_T33"
}
]
},
{
"id": "8641353_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"augmentation"
],
"offsets": [
[
1882,
1894
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_E16"
}
]
},
{
"id": "8641353_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1907,
1917
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T20"
}
]
},
{
"id": "8641353_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"present"
],
"offsets": [
[
1980,
1987
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T22"
}
]
},
{
"id": "8641353_E18",
"type": "Gene_expression",
"trigger": {
"text": [
"present"
],
"offsets": [
[
1980,
1987
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T21"
}
]
},
{
"id": "8641353_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
2063,
2071
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T24"
}
]
},
{
"id": "8641353_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
2141,
2149
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8641353_T25"
}
]
}
] | [
{
"id": "8641353_1",
"entity_ids": [
"8641353_T8",
"8641353_T9"
]
},
{
"id": "8641353_2",
"entity_ids": [
"8641353_T4",
"8641353_T5"
]
},
{
"id": "8641353_3",
"entity_ids": [
"8641353_T6",
"8641353_T7"
]
}
] | [] |
9379002 | 9379002 | [
{
"id": "9379002__text",
"type": "abstract",
"text": [
"Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis. \nBlood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients. The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes. "
],
"offsets": [
[
0,
1824
]
]
}
] | [
{
"id": "9379002_T1",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
55,
70
]
],
"normalized": []
},
{
"id": "9379002_T2",
"type": "Protein",
"text": [
"MAD-3"
],
"offsets": [
[
71,
76
]
],
"normalized": []
},
{
"id": "9379002_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
322,
331
]
],
"normalized": []
},
{
"id": "9379002_T4",
"type": "Protein",
"text": [
"IL-2R"
],
"offsets": [
[
367,
372
]
],
"normalized": []
},
{
"id": "9379002_T5",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
762,
777
]
],
"normalized": []
},
{
"id": "9379002_T6",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
936,
951
]
],
"normalized": []
},
{
"id": "9379002_T7",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
1207,
1222
]
],
"normalized": []
},
{
"id": "9379002_T8",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1506,
1510
]
],
"normalized": []
},
{
"id": "9379002_T9",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
1515,
1524
]
],
"normalized": []
},
{
"id": "9379002_T10",
"type": "Protein",
"text": [
"tuberculin"
],
"offsets": [
[
1613,
1623
]
],
"normalized": []
},
{
"id": "9379002_T11",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
1681,
1696
]
],
"normalized": []
},
{
"id": "9379002_T12",
"type": "Protein",
"text": [
"I kappa B-alpha"
],
"offsets": [
[
1719,
1734
]
],
"normalized": []
}
] | [
{
"id": "9379002_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T1"
}
]
},
{
"id": "9379002_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
249,
257
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E5"
}
]
},
{
"id": "9379002_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
249,
257
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E6"
}
]
},
{
"id": "9379002_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
265,
275
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E5"
}
]
},
{
"id": "9379002_E5",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
276,
283
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T3"
}
]
},
{
"id": "9379002_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"spontaneous expression"
],
"offsets": [
[
341,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T4"
}
]
},
{
"id": "9379002_E7",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
747,
758
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T5"
}
]
},
{
"id": "9379002_E8",
"type": "Protein_catabolism",
"trigger": {
"text": [
"intact"
],
"offsets": [
[
1066,
1072
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T6"
}
]
},
{
"id": "9379002_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1193,
1203
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T7"
}
]
},
{
"id": "9379002_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1252,
1262
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E9"
}
]
},
{
"id": "9379002_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulated"
],
"offsets": [
[
1282,
1294
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E9"
}
]
},
{
"id": "9379002_E12",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1444,
1454
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T9"
}
]
},
{
"id": "9379002_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1444,
1454
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T8"
}
]
},
{
"id": "9379002_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulated"
],
"offsets": [
[
1534,
1546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E13"
}
]
},
{
"id": "9379002_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulated"
],
"offsets": [
[
1534,
1546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E12"
}
]
},
{
"id": "9379002_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1654,
1661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E20"
},
{
"role": "Cause",
"ref_id": "9379002_T10"
}
]
},
{
"id": "9379002_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1654,
1661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E21"
},
{
"role": "Cause",
"ref_id": "9379002_T10"
}
]
},
{
"id": "9379002_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1654,
1661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E21"
}
]
},
{
"id": "9379002_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1654,
1661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_E20"
}
]
},
{
"id": "9379002_E20",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
1666,
1677
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T11"
}
]
},
{
"id": "9379002_E21",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1705,
1715
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9379002_T12"
}
]
}
] | [
{
"id": "9379002_1",
"entity_ids": [
"9379002_T1",
"9379002_T2"
]
}
] | [] |
9224625 | 9224625 | [
{
"id": "9224625__text",
"type": "abstract",
"text": [
"Role of ascorbate in the activation of NF-kappaB by tumour necrosis factor-alpha in T-cells. \nThe first product of ascorbate oxidation, the ascorbate free radical (AFR), acts in biological systems mainly as an oxidant, and through its role in the plasma membrane redox system exerts different effects on the cell. We have investigated the role of ascorbate, AFR and dehydroascorbate (DHA) in the activation of the NF-kappaB transcription factor in Jurkat T-cells stimulated by tumour necrosis factor-alpha (TNF-alpha). Here we show, by electrophoretic mobility shift assays, that ascorbate increases the binding of NF-kappaB to DNA in TNF-alpha-stimulated Jurkat cells. The ability of ascorbate to enhance cytoplasmic inhibitory IkBalpha protein degradation correlates completely with its capacity to induce NF-kappaB binding to DNA and to potentiate NF-kappaB-mediated transactivation of the HIV-1 long terminal repeat promoter in TNF-alpha-stimulated Jurkat cells but not in cells stimulated with PMA plus ionomycin. AFR behaves like ascorbate, while DHA and ascorbate phosphate do not affect TNF-alpha-mediated NF-kappaB activation. These results provide new evidence for a possible relationship between the activation of the electron-transport system at the plasma membrane by ascorbate or its free radical and redox-dependent gene transcription in T-cells. "
],
"offsets": [
[
0,
1362
]
]
}
] | [
{
"id": "9224625_T1",
"type": "Protein",
"text": [
"tumour necrosis factor-alpha"
],
"offsets": [
[
52,
80
]
],
"normalized": []
},
{
"id": "9224625_T2",
"type": "Protein",
"text": [
"tumour necrosis factor-alpha"
],
"offsets": [
[
477,
505
]
],
"normalized": []
},
{
"id": "9224625_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
507,
516
]
],
"normalized": []
},
{
"id": "9224625_T4",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
635,
644
]
],
"normalized": []
},
{
"id": "9224625_T5",
"type": "Protein",
"text": [
"IkBalpha"
],
"offsets": [
[
729,
737
]
],
"normalized": []
},
{
"id": "9224625_T6",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
932,
941
]
],
"normalized": []
},
{
"id": "9224625_T7",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1095,
1104
]
],
"normalized": []
}
] | [
{
"id": "9224625_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhance"
],
"offsets": [
[
698,
705
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9224625_E2"
}
]
},
{
"id": "9224625_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
746,
757
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9224625_T5"
}
]
}
] | [
{
"id": "9224625_1",
"entity_ids": [
"9224625_T2",
"9224625_T3"
]
}
] | [] |
1510878 | 1510878 | [
{
"id": "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": "1510878_T1",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
41,
46
]
],
"normalized": []
},
{
"id": "1510878_T2",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
51,
56
]
],
"normalized": []
},
{
"id": "1510878_T3",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
174,
179
]
],
"normalized": []
},
{
"id": "1510878_T4",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
184,
189
]
],
"normalized": []
},
{
"id": "1510878_T5",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
300,
305
]
],
"normalized": []
},
{
"id": "1510878_T6",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
310,
315
]
],
"normalized": []
},
{
"id": "1510878_T7",
"type": "Protein",
"text": [
"Con A"
],
"offsets": [
[
352,
357
]
],
"normalized": []
},
{
"id": "1510878_T8",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
554,
559
]
],
"normalized": []
},
{
"id": "1510878_T9",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
564,
569
]
],
"normalized": []
},
{
"id": "1510878_T10",
"type": "Protein",
"text": [
"PKC"
],
"offsets": [
[
622,
625
]
],
"normalized": []
},
{
"id": "1510878_T11",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
665,
670
]
],
"normalized": []
},
{
"id": "1510878_T12",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
675,
680
]
],
"normalized": []
},
{
"id": "1510878_T13",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
797,
802
]
],
"normalized": []
},
{
"id": "1510878_T14",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
807,
812
]
],
"normalized": []
},
{
"id": "1510878_T15",
"type": "Protein",
"text": [
"PKC"
],
"offsets": [
[
908,
911
]
],
"normalized": []
},
{
"id": "1510878_T16",
"type": "Protein",
"text": [
"PKC"
],
"offsets": [
[
997,
1000
]
],
"normalized": []
},
{
"id": "1510878_T17",
"type": "Protein",
"text": [
"Con A"
],
"offsets": [
[
1058,
1063
]
],
"normalized": []
},
{
"id": "1510878_T18",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
1401,
1406
]
],
"normalized": []
},
{
"id": "1510878_T19",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
1411,
1416
]
],
"normalized": []
},
{
"id": "1510878_T20",
"type": "Protein",
"text": [
"PKC"
],
"offsets": [
[
1559,
1562
]
],
"normalized": []
}
] | [
{
"id": "1510878_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
31,
40
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T1"
}
]
},
{
"id": "1510878_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
31,
40
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T2"
}
]
},
{
"id": "1510878_E3",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
143,
149
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T3"
}
]
},
{
"id": "1510878_E4",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
143,
149
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T4"
}
]
},
{
"id": "1510878_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
336,
345
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T5"
}
]
},
{
"id": "1510878_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
336,
345
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T6"
}
]
},
{
"id": "1510878_E7",
"type": "Regulation",
"trigger": {
"text": [
"involvement"
],
"offsets": [
[
505,
516
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_E9"
}
]
},
{
"id": "1510878_E8",
"type": "Regulation",
"trigger": {
"text": [
"involvement"
],
"offsets": [
[
505,
516
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_E10"
}
]
},
{
"id": "1510878_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
570,
579
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T9"
}
]
},
{
"id": "1510878_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
570,
579
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T8"
}
]
},
{
"id": "1510878_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
612,
621
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T10"
}
]
},
{
"id": "1510878_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"mimicked the effect of the lectins"
],
"offsets": [
[
627,
661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T11"
}
]
},
{
"id": "1510878_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"mimicked the effect of the lectins"
],
"offsets": [
[
627,
661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T12"
}
]
},
{
"id": "1510878_E14",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
757,
763
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T11"
}
]
},
{
"id": "1510878_E15",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
757,
763
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T12"
}
]
},
{
"id": "1510878_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
785,
793
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_E18"
}
]
},
{
"id": "1510878_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
785,
793
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_E19"
}
]
},
{
"id": "1510878_E18",
"type": "Regulation",
"trigger": {
"text": [
"immunoreactivity"
],
"offsets": [
[
813,
829
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T14"
}
]
},
{
"id": "1510878_E19",
"type": "Regulation",
"trigger": {
"text": [
"immunoreactivity"
],
"offsets": [
[
813,
829
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T13"
}
]
},
{
"id": "1510878_E20",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
834,
843
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_E17"
}
]
},
{
"id": "1510878_E21",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitor"
],
"offsets": [
[
861,
870
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T15"
}
]
},
{
"id": "1510878_E22",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitor"
],
"offsets": [
[
972,
981
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T15"
}
]
},
{
"id": "1510878_E23",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitor"
],
"offsets": [
[
972,
981
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T16"
}
]
},
{
"id": "1510878_E24",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1387,
1395
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T19"
}
]
},
{
"id": "1510878_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1387,
1395
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T18"
}
]
},
{
"id": "1510878_E26",
"type": "Regulation",
"trigger": {
"text": [
"involve"
],
"offsets": [
[
1533,
1540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_E27"
}
]
},
{
"id": "1510878_E27",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1545,
1555
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1510878_T20"
}
]
}
] | [] | [] |
7522257 | 7522257 | [
{
"id": "7522257__text",
"type": "abstract",
"text": [
"Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3. \nCD14, a monocyte/macrophage receptor for the complex of LPS and LPS binding protein, is a differentiation marker for the monocyte/macrophage lineage. We have analyzed the regulation of CD14 expression during 1 alpha,25-dihydroxyvitamin D3 (VitD3)-induced monocytic differentiation. Using FACS, Northern blotting, and nuclear run-on analyses, we demonstrate that the up-regulation of CD14 expression during monocytic cell maturation is regulated mainly at the level of gene transcription, and that new protein synthesis is required for CD14 induction. We have recently cloned the CD14 5' upstream sequence and demonstrated its tissue-specific promoter activity. Using stable transfection of the monocytoid U937 cell line with a series of deletion mutants of the CD14 5' upstream sequence coupled to a reporter gene construct, we show that bp -128 to -70 is the critical region for the induction of CD14 expression. This region contains two binding sites for the Sp1 transcription factor. A 3-bp mutation at the distal Sp1-binding site not only eliminates Sp1 interaction, but also abolishes most of the VitD3 induction of CD14 expression. Electrophoretic mobility shift analysis does not detect a direct interaction of the CD14 distal Sp1-binding site with the vitamin D3 receptor and its partner, the retinoid X receptor. These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor, and suggest a critical role for Sp1 in this process. "
],
"offsets": [
[
0,
1576
]
]
}
] | [
{
"id": "7522257_T1",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
14,
18
]
],
"normalized": []
},
{
"id": "7522257_T2",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
109,
113
]
],
"normalized": []
},
{
"id": "7522257_T3",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
294,
298
]
],
"normalized": []
},
{
"id": "7522257_T4",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
492,
496
]
],
"normalized": []
},
{
"id": "7522257_T5",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
644,
648
]
],
"normalized": []
},
{
"id": "7522257_T6",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
688,
692
]
],
"normalized": []
},
{
"id": "7522257_T7",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
870,
874
]
],
"normalized": []
},
{
"id": "7522257_T8",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
1006,
1010
]
],
"normalized": []
},
{
"id": "7522257_T9",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1070,
1073
]
],
"normalized": []
},
{
"id": "7522257_T10",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1126,
1129
]
],
"normalized": []
},
{
"id": "7522257_T11",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1163,
1166
]
],
"normalized": []
},
{
"id": "7522257_T12",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
1230,
1234
]
],
"normalized": []
},
{
"id": "7522257_T13",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
1331,
1335
]
],
"normalized": []
},
{
"id": "7522257_T14",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1343,
1346
]
],
"normalized": []
},
{
"id": "7522257_T15",
"type": "Protein",
"text": [
"vitamin D3 receptor"
],
"offsets": [
[
1369,
1388
]
],
"normalized": []
},
{
"id": "7522257_T16",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
1473,
1477
]
],
"normalized": []
},
{
"id": "7522257_T17",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1555,
1558
]
],
"normalized": []
}
] | [
{
"id": "7522257_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E2"
}
]
},
{
"id": "7522257_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
19,
29
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T1"
}
]
},
{
"id": "7522257_E3",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
280,
290
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E4"
}
]
},
{
"id": "7522257_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
299,
309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T3"
}
]
},
{
"id": "7522257_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
475,
488
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E6"
}
]
},
{
"id": "7522257_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
497,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T4"
}
]
},
{
"id": "7522257_E7",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
544,
553
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E5"
},
{
"role": "Cause",
"ref_id": "7522257_E8"
}
]
},
{
"id": "7522257_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"level"
],
"offsets": [
[
568,
573
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E9"
}
]
},
{
"id": "7522257_E9",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
582,
595
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T4"
}
]
},
{
"id": "7522257_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
631,
639
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E11"
}
]
},
{
"id": "7522257_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
649,
658
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T5"
}
]
},
{
"id": "7522257_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
993,
1002
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E13"
}
]
},
{
"id": "7522257_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1011,
1021
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T8"
}
]
},
{
"id": "7522257_E14",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1048,
1055
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T9"
}
]
},
{
"id": "7522257_E15",
"type": "Negative_regulation",
"trigger": {
"text": [
"eliminates"
],
"offsets": [
[
1152,
1162
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E16"
}
]
},
{
"id": "7522257_E16",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1167,
1178
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T11"
}
]
},
{
"id": "7522257_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"abolishes"
],
"offsets": [
[
1189,
1198
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E18"
}
]
},
{
"id": "7522257_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1217,
1226
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_E19"
}
]
},
{
"id": "7522257_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1235,
1245
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T12"
}
]
},
{
"id": "7522257_E20",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1312,
1323
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T15"
}
]
},
{
"id": "7522257_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"through"
],
"offsets": [
[
1489,
1496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T16"
}
]
},
{
"id": "7522257_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"critical role"
],
"offsets": [
[
1537,
1550
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7522257_T17"
}
]
}
] | [] | [] |
8264604 | 8264604 | [
{
"id": "8264604__text",
"type": "abstract",
"text": [
"The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor. \nThe macrophage colony-stimulating factor (M-CSF) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta. In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage, we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process. Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion. Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor, we investigated whether PU.1 binds and activates the M-CSF receptor promoter. Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site. Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only. Furthermore, PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells. These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor. "
],
"offsets": [
[
0,
1581
]
]
}
] | [
{
"id": "8264604_T1",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
36,
40
]
],
"normalized": []
},
{
"id": "8264604_T2",
"type": "Protein",
"text": [
"macrophage colony-stimulating factor receptor"
],
"offsets": [
[
83,
128
]
],
"normalized": []
},
{
"id": "8264604_T3",
"type": "Protein",
"text": [
"macrophage colony-stimulating factor (M-CSF) receptor"
],
"offsets": [
[
135,
188
]
],
"normalized": []
},
{
"id": "8264604_T4",
"type": "Protein",
"text": [
"M-CSF receptor"
],
"offsets": [
[
530,
544
]
],
"normalized": []
},
{
"id": "8264604_T5",
"type": "Protein",
"text": [
"M-CSF receptor"
],
"offsets": [
[
646,
660
]
],
"normalized": []
},
{
"id": "8264604_T6",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
876,
880
]
],
"normalized": []
},
{
"id": "8264604_T7",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
927,
931
]
],
"normalized": []
},
{
"id": "8264604_T8",
"type": "Protein",
"text": [
"M-CSF receptor"
],
"offsets": [
[
956,
970
]
],
"normalized": []
},
{
"id": "8264604_T9",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1031,
1035
]
],
"normalized": []
},
{
"id": "8264604_T10",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1040,
1044
]
],
"normalized": []
},
{
"id": "8264604_T11",
"type": "Protein",
"text": [
"M-CSF receptor"
],
"offsets": [
[
1098,
1112
]
],
"normalized": []
},
{
"id": "8264604_T12",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1221,
1225
]
],
"normalized": []
},
{
"id": "8264604_T13",
"type": "Protein",
"text": [
"M-CSF receptor"
],
"offsets": [
[
1243,
1257
]
],
"normalized": []
},
{
"id": "8264604_T14",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1334,
1338
]
],
"normalized": []
},
{
"id": "8264604_T15",
"type": "Protein",
"text": [
"M-CSF receptor"
],
"offsets": [
[
1358,
1372
]
],
"normalized": []
},
{
"id": "8264604_T16",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1433,
1437
]
],
"normalized": []
},
{
"id": "8264604_T24",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
971,
979
]
],
"normalized": []
},
{
"id": "8264604_T26",
"type": "Entity",
"text": [
"specific site"
],
"offsets": [
[
1077,
1090
]
],
"normalized": []
},
{
"id": "8264604_T27",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1113,
1121
]
],
"normalized": []
},
{
"id": "8264604_T31",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1258,
1266
]
],
"normalized": []
},
{
"id": "8264604_T33",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
1373,
1381
]
],
"normalized": []
}
] | [
{
"id": "8264604_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"directs"
],
"offsets": [
[
41,
48
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_E2"
},
{
"role": "Cause",
"ref_id": "8264604_T1"
}
]
},
{
"id": "8264604_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
65,
75
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T2"
}
]
},
{
"id": "8264604_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
192,
201
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T3"
}
]
},
{
"id": "8264604_E4",
"type": "Regulation",
"trigger": {
"text": [
"from"
],
"offsets": [
[
231,
235
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_E3"
}
]
},
{
"id": "8264604_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"activate"
],
"offsets": [
[
517,
525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T4"
}
]
},
{
"id": "8264604_E6",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
932,
937
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T7"
},
{
"role": "Theme",
"ref_id": "8264604_T8"
},
{
"role": "Site",
"ref_id": "8264604_T24"
}
]
},
{
"id": "8264604_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
942,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T8"
},
{
"role": "Cause",
"ref_id": "8264604_T7"
},
{
"role": "Site",
"ref_id": "8264604_T24"
}
]
},
{
"id": "8264604_E8",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
1067,
1071
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T10"
},
{
"role": "Theme",
"ref_id": "8264604_T11"
},
{
"role": "Site",
"ref_id": "8264604_T27"
}
]
},
{
"id": "8264604_E9",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
1067,
1071
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T9"
},
{
"role": "Theme",
"ref_id": "8264604_T11"
},
{
"role": "Site",
"ref_id": "8264604_T27"
}
]
},
{
"id": "8264604_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"eliminate"
],
"offsets": [
[
1211,
1220
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_E11"
}
]
},
{
"id": "8264604_E11",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1226,
1233
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T12"
},
{
"role": "Theme",
"ref_id": "8264604_T11"
},
{
"role": "Site",
"ref_id": "8264604_T26"
}
]
},
{
"id": "8264604_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"decrease"
],
"offsets": [
[
1234,
1242
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T13"
},
{
"role": "Cause",
"ref_id": "8264604_E10"
},
{
"role": "Site",
"ref_id": "8264604_T31"
}
]
},
{
"id": "8264604_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivates"
],
"offsets": [
[
1339,
1353
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8264604_T15"
},
{
"role": "Cause",
"ref_id": "8264604_T14"
},
{
"role": "Site",
"ref_id": "8264604_T33"
}
]
}
] | [] | [] |
8805630 | 8805630 | [
{
"id": "8805630__text",
"type": "abstract",
"text": [
"Multifactor cis-dominant negative regulation of IL-2 gene expression in anergized T cells. \nThe molecular mechanism underlying IL-2 transcriptional blockade in anergic T cell clones is not fully understood. To examine whether an active negative regulatory process occurs, we created a reporter construct containing as an enhancer four copies of the NF-AT site and one copy of the octamer site (4X NF-AT-Oct). This construct was only slightly reduced (1.3-fold) in its expression when stimulated under anergic conditions, while a whole mouse IL-2 enhancer construct showed a reduction of 4.3-fold. Addition of the -176 to -96 sequence to the 4X NF-AT-Oct construct did not impart the ability to be affected by anergy, but addition of the -236 to -96 sequence did, demonstrating that anergy is an active inhibitory process and that more than the presence of the -150 AP-1 binding site (-152 to -147) is required to mediate the effect. Mutational studies of the -236 to -96 sequence indicated that the presence of both the -130 AP-1-like site (-187 to -181) and the -150 proximal AP-1 site were necessary to observe anergy. Because the -180 site is not required for trans-activation, it was possible to confirm by mutation in the normal mouse IL-2 enhancer that this site is absolutely essential for anergy induction. The simplest model to explain these results is that anergy is mediated by a complex of multiple transcription factors that exert a cis-acting dominant negative regulatory effect on the trans-activation of the IL-2 gene. "
],
"offsets": [
[
0,
1535
]
]
}
] | [
{
"id": "8805630_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
48,
52
]
],
"normalized": []
},
{
"id": "8805630_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
127,
131
]
],
"normalized": []
},
{
"id": "8805630_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
541,
545
]
],
"normalized": []
},
{
"id": "8805630_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1240,
1244
]
],
"normalized": []
},
{
"id": "8805630_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1524,
1528
]
],
"normalized": []
}
] | [
{
"id": "8805630_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"dominant negative regulation"
],
"offsets": [
[
16,
44
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8805630_E2"
}
]
},
{
"id": "8805630_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
58,
68
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8805630_T1"
}
]
},
{
"id": "8805630_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"transcriptional blockade"
],
"offsets": [
[
132,
156
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8805630_T2"
}
]
},
{
"id": "8805630_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"exert"
],
"offsets": [
[
1438,
1443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8805630_E5"
}
]
},
{
"id": "8805630_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"dominant negative regulatory effect"
],
"offsets": [
[
1457,
1492
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8805630_E6"
}
]
},
{
"id": "8805630_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"trans-activation"
],
"offsets": [
[
1500,
1516
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8805630_T5"
}
]
}
] | [] | [] |
1560002 | 1560002 | [
{
"id": "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": "1560002_T1",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
35,
40
]
],
"normalized": []
},
{
"id": "1560002_T2",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
120,
123
]
],
"normalized": []
},
{
"id": "1560002_T3",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
185,
188
]
],
"normalized": []
},
{
"id": "1560002_T4",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
259,
262
]
],
"normalized": []
},
{
"id": "1560002_T5",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
395,
400
]
],
"normalized": []
},
{
"id": "1560002_T6",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
420,
425
]
],
"normalized": []
},
{
"id": "1560002_T7",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
466,
471
]
],
"normalized": []
},
{
"id": "1560002_T8",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
480,
485
]
],
"normalized": []
},
{
"id": "1560002_T9",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
500,
503
]
],
"normalized": []
},
{
"id": "1560002_T10",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
607,
612
]
],
"normalized": []
},
{
"id": "1560002_T11",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
656,
661
]
],
"normalized": []
},
{
"id": "1560002_T12",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
665,
668
]
],
"normalized": []
},
{
"id": "1560002_T13",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
702,
707
]
],
"normalized": []
},
{
"id": "1560002_T14",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
750,
753
]
],
"normalized": []
},
{
"id": "1560002_T15",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
854,
859
]
],
"normalized": []
},
{
"id": "1560002_T16",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
934,
937
]
],
"normalized": []
},
{
"id": "1560002_T17",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1019,
1024
]
],
"normalized": []
},
{
"id": "1560002_T18",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1078,
1083
]
],
"normalized": []
},
{
"id": "1560002_T19",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
1101,
1104
]
],
"normalized": []
},
{
"id": "1560002_T20",
"type": "Protein",
"text": [
"DRA"
],
"offsets": [
[
1313,
1316
]
],
"normalized": []
},
{
"id": "1560002_T23",
"type": "Entity",
"text": [
"ATTTGCAT"
],
"offsets": [
[
218,
226
]
],
"normalized": []
}
] | [
{
"id": "1560002_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"positively regulates"
],
"offsets": [
[
41,
61
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E2"
},
{
"role": "Cause",
"ref_id": "1560002_T1"
}
]
},
{
"id": "1560002_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
62,
75
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T2"
}
]
},
{
"id": "1560002_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
236,
244
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E4"
},
{
"role": "Cause",
"ref_id": "1560002_T3"
},
{
"role": "CSite",
"ref_id": "1560002_T23"
}
]
},
{
"id": "1560002_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
263,
273
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T4"
}
]
},
{
"id": "1560002_E5",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
328,
332
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T3"
},
{
"role": "Site",
"ref_id": "1560002_T23"
}
]
},
{
"id": "1560002_E6",
"type": "Regulation",
"trigger": {
"text": [
"regulates"
],
"offsets": [
[
486,
495
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T9"
},
{
"role": "Cause",
"ref_id": "1560002_T8"
}
]
},
{
"id": "1560002_E7",
"type": "Regulation",
"trigger": {
"text": [
"regulates"
],
"offsets": [
[
486,
495
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T9"
},
{
"role": "Cause",
"ref_id": "1560002_T7"
}
]
},
{
"id": "1560002_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
647,
651
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E9"
},
{
"role": "Cause",
"ref_id": "1560002_T11"
}
]
},
{
"id": "1560002_E9",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
674,
687
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T12"
}
]
},
{
"id": "1560002_E10",
"type": "Regulation",
"trigger": {
"text": [
"affect"
],
"offsets": [
[
743,
749
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E11"
},
{
"role": "Cause",
"ref_id": "1560002_T13"
}
]
},
{
"id": "1560002_E11",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
759,
772
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T14"
}
]
},
{
"id": "1560002_E12",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
889,
902
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T15"
}
]
},
{
"id": "1560002_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhance"
],
"offsets": [
[
926,
933
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E14"
},
{
"role": "Cause",
"ref_id": "1560002_T15"
}
]
},
{
"id": "1560002_E14",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
943,
956
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T16"
}
]
},
{
"id": "1560002_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
1092,
1100
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E16"
},
{
"role": "Cause",
"ref_id": "1560002_T18"
}
]
},
{
"id": "1560002_E16",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1110,
1123
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T19"
}
]
},
{
"id": "1560002_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"requires"
],
"offsets": [
[
1146,
1154
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E15"
}
]
},
{
"id": "1560002_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"positive role"
],
"offsets": [
[
1247,
1260
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_E19"
}
]
},
{
"id": "1560002_E19",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1322,
1335
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1560002_T20"
}
]
}
] | [] | [] |
7742037 | 7742037 | [
{
"id": "7742037__text",
"type": "abstract",
"text": [
"HIV type 1 protease activation of NF-kappa B within T lymphoid cells. \nNF-kappa B is a nuclear protein of the rel oncogene family capable of enhancing transcription of several cellular genes, including IL-2 and the IL-2 receptor, and viral genes transcribed from the HIV-1 LTR. It has been reported that HIV-1 protease may cleave the NF-kappa B precursor to its active form in vitro. In this study the effects of HIV protease on NF-kappa B precursor activation were examined in Jurkat T cells by introducing a protease expression vector into the cells. Increased NF-kappa B activity was observed and this increased activity was blocked by a specific inhibitor of the viral protease. Viral transcription, as measured using LTR-CAT assays, was only slightly enhanced in the HIV-protease expressing cells, while secretion of IL-2 and expression of the IL-2 receptor were not affected. The limited activation of NF-kappa B by HIV protease appears unlikely to have a significant effect on virus expression or T cell function. "
],
"offsets": [
[
0,
1021
]
]
}
] | [
{
"id": "7742037_T1",
"type": "Protein",
"text": [
"HIV type 1 protease"
],
"offsets": [
[
0,
19
]
],
"normalized": []
},
{
"id": "7742037_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
202,
206
]
],
"normalized": []
},
{
"id": "7742037_T3",
"type": "Protein",
"text": [
"HIV-1 protease"
],
"offsets": [
[
304,
318
]
],
"normalized": []
},
{
"id": "7742037_T4",
"type": "Protein",
"text": [
"HIV protease"
],
"offsets": [
[
413,
425
]
],
"normalized": []
},
{
"id": "7742037_T5",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
726,
729
]
],
"normalized": []
},
{
"id": "7742037_T6",
"type": "Protein",
"text": [
"HIV-protease"
],
"offsets": [
[
772,
784
]
],
"normalized": []
},
{
"id": "7742037_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
822,
826
]
],
"normalized": []
},
{
"id": "7742037_T8",
"type": "Protein",
"text": [
"HIV protease"
],
"offsets": [
[
922,
934
]
],
"normalized": []
}
] | [
{
"id": "7742037_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhancing"
],
"offsets": [
[
141,
150
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_E2"
}
]
},
{
"id": "7742037_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
151,
164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_T2"
}
]
},
{
"id": "7742037_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"introducing"
],
"offsets": [
[
496,
507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_E4"
}
]
},
{
"id": "7742037_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
519,
529
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_T4"
}
]
},
{
"id": "7742037_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitor"
],
"offsets": [
[
650,
659
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_T4"
}
]
},
{
"id": "7742037_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
785,
795
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_T6"
}
]
},
{
"id": "7742037_E7",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
809,
818
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_T7"
}
]
},
{
"id": "7742037_E8",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
872,
880
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7742037_E7"
}
]
}
] | [] | [] |
9309306 | 9309306 | [
{
"id": "9309306__text",
"type": "abstract",
"text": [
"Alcohol-induced regulation of nuclear regulatory factor-kappa beta in human monocytes. \nAcute ethanol exposure has the capacity to modulate immune functions, particularly, to down regulate monocyte production of inflammatory cytokines. However, the intracellular mechanisms for these effects of ethanol are yet to be understood. Considering that nuclear regulatory factor-kappa beta (NF-kappa B)/Rel is a common regulatory element of the promoter region of the inflammatory cytokine genes, herein, we tested the hypothesis that acute ethanol affects NF-kappa B activation in human monocytes. Adherence-isolated monocytes showed constitutive DNA binding activity of NF-kappa B. A clinically relevant dose (25 mM) of acute ethanol treatment in vitro increased NF-kappa B binding activity in monocytes with a preferential induction of the inhibitory, p50/p50, NF-kappa B/Rel homodimer, and resulted in no induction of the p65/p50 heterodimer. In contrast, lipopolysaccharide stimulation primarily induced the p65/p50 heterodimer that has been shown to result in gene activation. Thus, such unique activation of the inhibitory p50/p50 homodimer by acute ethanol treatment may result in inhibition rather than activation of NF-kappa B-regulated inflammatory cytokine genes. Consequently, these results suggest that physiologically relevant concentrations of ethanol may affect production of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 by disrupting NF-kappa B signaling in monocytes. "
],
"offsets": [
[
0,
1534
]
]
}
] | [
{
"id": "9309306_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
848,
851
]
],
"normalized": []
},
{
"id": "9309306_T2",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
852,
855
]
],
"normalized": []
},
{
"id": "9309306_T3",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
919,
922
]
],
"normalized": []
},
{
"id": "9309306_T4",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
923,
926
]
],
"normalized": []
},
{
"id": "9309306_T5",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1006,
1009
]
],
"normalized": []
},
{
"id": "9309306_T6",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1010,
1013
]
],
"normalized": []
},
{
"id": "9309306_T7",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1123,
1126
]
],
"normalized": []
},
{
"id": "9309306_T8",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1127,
1130
]
],
"normalized": []
},
{
"id": "9309306_T9",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
1418,
1445
]
],
"normalized": []
},
{
"id": "9309306_T10",
"type": "Protein",
"text": [
"interleukin-1 beta"
],
"offsets": [
[
1447,
1465
]
],
"normalized": []
},
{
"id": "9309306_T11",
"type": "Protein",
"text": [
"interleukin-6"
],
"offsets": [
[
1471,
1484
]
],
"normalized": []
}
] | [
{
"id": "9309306_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
819,
828
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T1"
}
]
},
{
"id": "9309306_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
994,
1001
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T6"
}
]
},
{
"id": "9309306_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
994,
1001
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T5"
}
]
},
{
"id": "9309306_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1094,
1104
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T7"
}
]
},
{
"id": "9309306_E5",
"type": "Regulation",
"trigger": {
"text": [
"affect"
],
"offsets": [
[
1365,
1371
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_E9"
}
]
},
{
"id": "9309306_E6",
"type": "Regulation",
"trigger": {
"text": [
"affect"
],
"offsets": [
[
1365,
1371
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_E10"
}
]
},
{
"id": "9309306_E7",
"type": "Regulation",
"trigger": {
"text": [
"affect"
],
"offsets": [
[
1365,
1371
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_E8"
}
]
},
{
"id": "9309306_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1372,
1382
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T11"
}
]
},
{
"id": "9309306_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1372,
1382
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T10"
}
]
},
{
"id": "9309306_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1372,
1382
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9309306_T9"
}
]
}
] | [
{
"id": "9309306_1",
"entity_ids": [
"9309306_T1",
"9309306_T2"
]
},
{
"id": "9309306_2",
"entity_ids": [
"9309306_T7",
"9309306_T8"
]
}
] | [] |
7706235 | 7706235 | [
{
"id": "7706235__text",
"type": "abstract",
"text": [
"Nitric oxide-stimulated guanine nucleotide exchange on p21ras. \nThe protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events. Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange. Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell. These studies identify p21ras as a target of the same cell. These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors. "
],
"offsets": [
[
0,
1124
]
]
}
] | [
{
"id": "7706235_T1",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
55,
61
]
],
"normalized": []
},
{
"id": "7706235_T2",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
82,
88
]
],
"normalized": []
},
{
"id": "7706235_T3",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
273,
279
]
],
"normalized": []
},
{
"id": "7706235_T4",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
338,
344
]
],
"normalized": []
},
{
"id": "7706235_T5",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
386,
392
]
],
"normalized": []
},
{
"id": "7706235_T6",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
539,
545
]
],
"normalized": []
},
{
"id": "7706235_T7",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
748,
754
]
],
"normalized": []
},
{
"id": "7706235_T8",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
872,
878
]
],
"normalized": []
},
{
"id": "7706235_T9",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
920,
926
]
],
"normalized": []
},
{
"id": "7706235_T10",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
980,
986
]
],
"normalized": []
},
{
"id": "7706235_T11",
"type": "Protein",
"text": [
"p21ras"
],
"offsets": [
[
1046,
1052
]
],
"normalized": []
}
] | [
{
"id": "7706235_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
263,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7706235_T3"
}
]
},
{
"id": "7706235_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
316,
324
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7706235_T4"
}
]
},
{
"id": "7706235_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activate"
],
"offsets": [
[
863,
871
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7706235_T8"
}
]
},
{
"id": "7706235_E4",
"type": "Regulation",
"trigger": {
"text": [
"target"
],
"offsets": [
[
992,
998
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7706235_T10"
}
]
},
{
"id": "7706235_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
1036,
1045
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7706235_T11"
}
]
}
] | [] | [] |
9442380 | 9442380 | [
{
"id": "9442380__text",
"type": "abstract",
"text": [
"LPS tolerance in monocytes/macrophages: three 3' cytosins are required in the DNA binding motif for detection of upregulated NF-kappa B p50 homodimers. \nWhen monocytes are stimulated with LPS (lipopolysaccharide) repeatedly then the initially high expression of the TNF (tumor necrosis factor) gene is only very low, i.e. the cells are tolerant to LPS. Tolerant cells still express the CD14 receptor and they can still be activated to mobilize NF-kappa B into nucleus. Analysis of the binding proteins employing the -605 motif of the human TNF promoter (GGGGCTGTCCC) revealed that in tolerant cells of the human monocytic cell line Mono Mac 6 there is a predominance of p50p50 of NF-kappa B. We now show that a mutant motif that exchanges the terminal 3' C for a G fails to bind the p50 homodimer that is upregulated in LPS toler ant human Mono Mac 6 cells. The same is true for nuclear extracts taken from the murine P388D1 macrophage cell line when tested with the -516 motif of the murine TNF promoter (GGGGGCTTTCCC). Here the wild type motif gives efficient binding of p50p50 that again is upregulated in tolerant cells whereas a mutant with a 3' G shows hardly any binding of p50p50. Conversely, the murine kappa light chain enhancer motif (GGGGACTTTCCG) does not efficiently bind the nuclear p50p50 from tolerant murine P388 macrophages. Binding is, however, readily detected when the 3' G is replaced by a C. These data show that the detection of upregulated p50 homodimers in LPS tolerant cells is dependent on subtle differences in the sequence of the DNA binding motif. "
],
"offsets": [
[
0,
1580
]
]
}
] | [
{
"id": "9442380_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
136,
139
]
],
"normalized": []
},
{
"id": "9442380_T2",
"type": "Protein",
"text": [
"TNF"
],
"offsets": [
[
266,
269
]
],
"normalized": []
},
{
"id": "9442380_T3",
"type": "Protein",
"text": [
"tumor necrosis factor"
],
"offsets": [
[
271,
292
]
],
"normalized": []
},
{
"id": "9442380_T4",
"type": "Protein",
"text": [
"CD14 receptor"
],
"offsets": [
[
386,
399
]
],
"normalized": []
},
{
"id": "9442380_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
670,
673
]
],
"normalized": []
},
{
"id": "9442380_T6",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
673,
676
]
],
"normalized": []
},
{
"id": "9442380_T7",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
783,
786
]
],
"normalized": []
},
{
"id": "9442380_T8",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1073,
1076
]
],
"normalized": []
},
{
"id": "9442380_T9",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1076,
1079
]
],
"normalized": []
},
{
"id": "9442380_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1181,
1184
]
],
"normalized": []
},
{
"id": "9442380_T11",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1184,
1187
]
],
"normalized": []
},
{
"id": "9442380_T12",
"type": "Protein",
"text": [
"kappa light chain"
],
"offsets": [
[
1212,
1229
]
],
"normalized": []
},
{
"id": "9442380_T13",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1298,
1301
]
],
"normalized": []
},
{
"id": "9442380_T14",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1301,
1304
]
],
"normalized": []
},
{
"id": "9442380_T15",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1466,
1469
]
],
"normalized": []
},
{
"id": "9442380_T27",
"type": "Entity",
"text": [
"GGGGACTTTCCG"
],
"offsets": [
[
1246,
1258
]
],
"normalized": []
}
] | [
{
"id": "9442380_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
113,
124
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T1"
}
]
},
{
"id": "9442380_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
248,
258
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T2"
}
]
},
{
"id": "9442380_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"low"
],
"offsets": [
[
312,
315
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_E2"
}
]
},
{
"id": "9442380_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"express"
],
"offsets": [
[
374,
381
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T4"
}
]
},
{
"id": "9442380_E5",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
485,
492
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T5"
}
]
},
{
"id": "9442380_E6",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
485,
492
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T6"
}
]
},
{
"id": "9442380_E7",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
774,
778
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T7"
}
]
},
{
"id": "9442380_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
805,
816
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T7"
}
]
},
{
"id": "9442380_E9",
"type": "Binding",
"trigger": {
"text": [
"is true"
],
"offsets": [
[
867,
874
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T7"
}
]
},
{
"id": "9442380_E10",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1062,
1069
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T8"
}
]
},
{
"id": "9442380_E11",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1062,
1069
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T9"
}
]
},
{
"id": "9442380_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
1094,
1105
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T9"
}
]
},
{
"id": "9442380_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
1094,
1105
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T8"
}
]
},
{
"id": "9442380_E14",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1170,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T10"
}
]
},
{
"id": "9442380_E15",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1170,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T11"
}
]
},
{
"id": "9442380_E16",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
1281,
1285
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T12"
},
{
"role": "Theme",
"ref_id": "9442380_T13"
},
{
"role": "Site",
"ref_id": "9442380_T27"
}
]
},
{
"id": "9442380_E17",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
1281,
1285
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T12"
},
{
"role": "Theme",
"ref_id": "9442380_T14"
},
{
"role": "Site",
"ref_id": "9442380_T27"
}
]
},
{
"id": "9442380_E18",
"type": "Negative_regulation",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
1373,
1381
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_E16"
}
]
},
{
"id": "9442380_E19",
"type": "Negative_regulation",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
1373,
1381
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_E17"
}
]
},
{
"id": "9442380_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulated"
],
"offsets": [
[
1454,
1465
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_T15"
}
]
},
{
"id": "9442380_E21",
"type": "Regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
1506,
1515
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442380_E20"
}
]
}
] | [
{
"id": "9442380_1",
"entity_ids": [
"9442380_T2",
"9442380_T3"
]
}
] | [] |
7865130 | 7865130 | [
{
"id": "7865130__text",
"type": "abstract",
"text": [
"Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937. \nTo study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development, a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937. By extensive nucleotide sequence and Northern blot analysis, these cDNA clones were found to originate from approximately 42 different genes (HZF 1-42) of which only 8 have previously been described. Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells. The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues. In contrast, some of the genes displayed a restricted expression pattern, indicating that they represent potential regulators of monocyte differentiation or proliferation. Detailed structural analysis of the first 12 cDNAs (HZF 1-10) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel-related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins. In addition, several novel KRAB-containing zinc finger genes and a novel conserved sequence element were identified. "
],
"offsets": [
[
0,
1706
]
]
}
] | [
{
"id": "7865130_T1",
"type": "Protein",
"text": [
"HZF 1"
],
"offsets": [
[
649,
654
]
],
"normalized": []
},
{
"id": "7865130_T2",
"type": "Protein",
"text": [
"42"
],
"offsets": [
[
655,
657
]
],
"normalized": []
},
{
"id": "7865130_T3",
"type": "Protein",
"text": [
"HZF 1"
],
"offsets": [
[
1292,
1297
]
],
"normalized": []
},
{
"id": "7865130_T4",
"type": "Protein",
"text": [
"10"
],
"offsets": [
[
1298,
1300
]
],
"normalized": []
},
{
"id": "7865130_T5",
"type": "Protein",
"text": [
"HZF 11"
],
"offsets": [
[
1336,
1342
]
],
"normalized": []
},
{
"id": "7865130_T6",
"type": "Protein",
"text": [
"42"
],
"offsets": [
[
1343,
1345
]
],
"normalized": []
}
] | [
{
"id": "7865130_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
773,
782
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7865130_T2"
}
]
},
{
"id": "7865130_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
773,
782
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7865130_T1"
}
]
},
{
"id": "7865130_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
940,
950
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7865130_T1"
}
]
},
{
"id": "7865130_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
940,
950
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7865130_T2"
}
]
},
{
"id": "7865130_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1122,
1132
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7865130_T1"
}
]
}
] | [] | [] |
9414129 | 9414129 | [
{
"id": "9414129__text",
"type": "abstract",
"text": [
"c-Rel and p65 subunits bind to an upstream NF-kappaB site in human granulocyte macrophage-colony stimulating factor promoter involved in phorbol ester response in 5637 cells. \nTo further clarify the complex transcriptional regulation of the human GM-CSF gene, which was extensively investigated in activated T cells, we have studied the role of an upstream NF-kappaB like site in the 5637 non-lymphoid cell line, which derives from a bladder carcinoma and constitutively produces GM-CSF. This sequence, named the A element, has an active role on GM-CSF transcription and is responsive to the tumor promoter PMA in transient transfection experiments. We describe here a heterodimeric binding complex of NF-kappaB subunits (c-Rel and p65) which is identical to the one obtained using the HIV-LTR-kappaB site as recognition sequence and different from the one (c-Rel and p50) observed with nuclear extracts from Mo T-lymphoid HTLV-II infected cells. "
],
"offsets": [
[
0,
947
]
]
}
] | [
{
"id": "9414129_T1",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "9414129_T2",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
10,
13
]
],
"normalized": []
},
{
"id": "9414129_T3",
"type": "Protein",
"text": [
"granulocyte macrophage-colony stimulating factor"
],
"offsets": [
[
67,
115
]
],
"normalized": []
},
{
"id": "9414129_T4",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
247,
253
]
],
"normalized": []
},
{
"id": "9414129_T5",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
480,
486
]
],
"normalized": []
},
{
"id": "9414129_T6",
"type": "Protein",
"text": [
"GM-CSF"
],
"offsets": [
[
546,
552
]
],
"normalized": []
},
{
"id": "9414129_T7",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
722,
727
]
],
"normalized": []
},
{
"id": "9414129_T8",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "9414129_T9",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
858,
863
]
],
"normalized": []
},
{
"id": "9414129_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
868,
871
]
],
"normalized": []
}
] | [
{
"id": "9414129_E1",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
23,
27
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T2"
}
]
},
{
"id": "9414129_E2",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
23,
27
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T1"
}
]
},
{
"id": "9414129_E3",
"type": "Regulation",
"trigger": {
"text": [
"transcriptional regulation"
],
"offsets": [
[
207,
233
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T4"
}
]
},
{
"id": "9414129_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"produces"
],
"offsets": [
[
471,
479
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T5"
}
]
},
{
"id": "9414129_E5",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
538,
542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_E6"
}
]
},
{
"id": "9414129_E6",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
553,
566
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T6"
}
]
},
{
"id": "9414129_E7",
"type": "Binding",
"trigger": {
"text": [
"heterodimeric binding complex"
],
"offsets": [
[
669,
698
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T9"
},
{
"role": "Theme",
"ref_id": "9414129_T10"
}
]
},
{
"id": "9414129_E8",
"type": "Binding",
"trigger": {
"text": [
"heterodimeric binding complex"
],
"offsets": [
[
669,
698
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T7"
},
{
"role": "Theme",
"ref_id": "9414129_T8"
}
]
},
{
"id": "9414129_E9",
"type": "Binding",
"trigger": {
"text": [
"complex"
],
"offsets": [
[
691,
698
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T8"
}
]
},
{
"id": "9414129_E10",
"type": "Binding",
"trigger": {
"text": [
"complex"
],
"offsets": [
[
691,
698
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9414129_T7"
}
]
}
] | [] | [] |
8135784 | 8135784 | [
{
"id": "8135784__text",
"type": "abstract",
"text": [
"Characterization of NF(P), the nuclear factor that interacts with the regulatory P sequence (5'-CGAAAATTTCC-3') of the human interleukin-4 gene: relationship to NF-kappa B and NF-AT. \nThe P sequence of the human interleukin-4 (IL-4) gene, which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore (A23187) in Jurkat T cells, shares sequence similarity with the NF-kappa B and the NF-AT binding sites. We examined whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and NF-AT. NF-kappa B (P65 or P65/P50 heterodimer) bound to the P sequence in electrophoretic mobility shift assays (EMSA) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T cells. In EMSAs, NF(P) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence. Both mobility shift and sequence specificity of NF-AT were similar to those of NF(P) and only a small amount of P65 was detected in NF(P) in crude nuclear extracts. These results indicate that the component(s) of NF-AT has the potential to reconstitute NF(P) whereas NF-kappa B alone cannot account for NF(P) in crude extracts. Unlike NF-AT, NF(P) does not contain AP1 as its DNA binding component. "
],
"offsets": [
[
0,
1405
]
]
}
] | [
{
"id": "8135784_T1",
"type": "Protein",
"text": [
"interleukin-4"
],
"offsets": [
[
125,
138
]
],
"normalized": []
},
{
"id": "8135784_T2",
"type": "Protein",
"text": [
"interleukin-4"
],
"offsets": [
[
212,
225
]
],
"normalized": []
},
{
"id": "8135784_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
227,
231
]
],
"normalized": []
},
{
"id": "8135784_T4",
"type": "Protein",
"text": [
"P65"
],
"offsets": [
[
564,
567
]
],
"normalized": []
},
{
"id": "8135784_T5",
"type": "Protein",
"text": [
"P65"
],
"offsets": [
[
571,
574
]
],
"normalized": []
},
{
"id": "8135784_T6",
"type": "Protein",
"text": [
"P50"
],
"offsets": [
[
575,
578
]
],
"normalized": []
},
{
"id": "8135784_T7",
"type": "Protein",
"text": [
"P65"
],
"offsets": [
[
1118,
1121
]
],
"normalized": []
},
{
"id": "8135784_T9",
"type": "Entity",
"text": [
"P sequence"
],
"offsets": [
[
81,
91
]
],
"normalized": []
},
{
"id": "8135784_T10",
"type": "Entity",
"text": [
"P sequence"
],
"offsets": [
[
188,
198
]
],
"normalized": []
}
] | [
{
"id": "8135784_E1",
"type": "Binding",
"trigger": {
"text": [
"interacts"
],
"offsets": [
[
51,
60
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8135784_T1"
},
{
"role": "Site",
"ref_id": "8135784_T9"
}
]
},
{
"id": "8135784_E2",
"type": "Regulation",
"trigger": {
"text": [
"responsive element"
],
"offsets": [
[
262,
280
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8135784_T2"
},
{
"role": "Site",
"ref_id": "8135784_T10"
}
]
},
{
"id": "8135784_E3",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
592,
597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8135784_T5"
}
]
},
{
"id": "8135784_E4",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
592,
597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8135784_T6"
}
]
},
{
"id": "8135784_E5",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
592,
597
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8135784_T4"
}
]
},
{
"id": "8135784_E6",
"type": "Binding",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
1126,
1134
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8135784_T7"
}
]
}
] | [
{
"id": "8135784_1",
"entity_ids": [
"8135784_T2",
"8135784_T3"
]
}
] | [] |
8207793 | 8207793 | [
{
"id": "8207793__text",
"type": "abstract",
"text": [
"Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. \nDysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS. To investigate the effects of human immunodeficiency virus type 1 (HIV-1) Tat on interleukin-2 (IL-2) expression, we used IL-2 promoter-chloramphenicol acetyltransferase constructs and IL-2-secreting Jurkat T cells as a model system. Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate. IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein. Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level. The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect. The Tat-mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or-unlike the analogous effect of human T-cell lymphotropic virus type 1 Tax-by cyclosporin A. The observed increase in IL-2 levels might facilitate virus spread from or to T cells. Furthermore, it might contribute to the hypergammaglobulinemia or, together with other cytokines found to be dysregulated, the T-helper cell dysfunctions observed in AIDS patients. "
],
"offsets": [
[
0,
1437
]
]
}
] | [
{
"id": "8207793_T1",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
36,
39
]
],
"normalized": []
},
{
"id": "8207793_T2",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
52,
65
]
],
"normalized": []
},
{
"id": "8207793_T3",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
276,
279
]
],
"normalized": []
},
{
"id": "8207793_T4",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
283,
296
]
],
"normalized": []
},
{
"id": "8207793_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
298,
302
]
],
"normalized": []
},
{
"id": "8207793_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
324,
328
]
],
"normalized": []
},
{
"id": "8207793_T7",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
338,
371
]
],
"normalized": []
},
{
"id": "8207793_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
387,
391
]
],
"normalized": []
},
{
"id": "8207793_T9",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
466,
469
]
],
"normalized": []
},
{
"id": "8207793_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
511,
515
]
],
"normalized": []
},
{
"id": "8207793_T11",
"type": "Protein",
"text": [
"phytohemagglutinin"
],
"offsets": [
[
568,
586
]
],
"normalized": []
},
{
"id": "8207793_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
618,
622
]
],
"normalized": []
},
{
"id": "8207793_T13",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
742,
745
]
],
"normalized": []
},
{
"id": "8207793_T14",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
787,
790
]
],
"normalized": []
},
{
"id": "8207793_T15",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
812,
816
]
],
"normalized": []
},
{
"id": "8207793_T16",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
910,
914
]
],
"normalized": []
},
{
"id": "8207793_T17",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
964,
967
]
],
"normalized": []
},
{
"id": "8207793_T18",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
980,
983
]
],
"normalized": []
},
{
"id": "8207793_T19",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1005,
1009
]
],
"normalized": []
},
{
"id": "8207793_T20",
"type": "Protein",
"text": [
"tat"
],
"offsets": [
[
1070,
1073
]
],
"normalized": []
},
{
"id": "8207793_T21",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1147,
1150
]
],
"normalized": []
},
{
"id": "8207793_T22",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1194,
1198
]
],
"normalized": []
}
] | [
{
"id": "8207793_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulates"
],
"offsets": [
[
40,
51
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_E2"
},
{
"role": "Cause",
"ref_id": "8207793_T1"
}
]
},
{
"id": "8207793_E2",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
66,
75
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_T2"
}
]
},
{
"id": "8207793_E3",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
221,
228
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_E4"
},
{
"role": "Cause",
"ref_id": "8207793_T3"
}
]
},
{
"id": "8207793_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
304,
314
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_T5"
}
]
},
{
"id": "8207793_E5",
"type": "Localization",
"trigger": {
"text": [
"secreting"
],
"offsets": [
[
392,
401
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_T8"
}
]
},
{
"id": "8207793_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
446,
456
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_T9"
}
]
},
{
"id": "8207793_E7",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
623,
632
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_T12"
}
]
},
{
"id": "8207793_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
637,
646
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_E7"
}
]
},
{
"id": "8207793_E9",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
802,
808
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_E10"
},
{
"role": "Cause",
"ref_id": "8207793_T14"
}
]
},
{
"id": "8207793_E10",
"type": "Transcription",
"trigger": {
"text": [
"transcriptional"
],
"offsets": [
[
834,
849
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8207793_T15"
}
]
}
] | [
{
"id": "8207793_1",
"entity_ids": [
"8207793_T4",
"8207793_T5"
]
}
] | [] |
10423406 | 10423406 | [
{
"id": "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": "10423406_T1",
"type": "Protein",
"text": [
"interleukin-8"
],
"offsets": [
[
26,
39
]
],
"normalized": []
},
{
"id": "10423406_T2",
"type": "Protein",
"text": [
"eosinophil granule major basic protein"
],
"offsets": [
[
54,
92
]
],
"normalized": []
},
{
"id": "10423406_T3",
"type": "Protein",
"text": [
"eosinophil granule major basic protein"
],
"offsets": [
[
123,
161
]
],
"normalized": []
},
{
"id": "10423406_T4",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
163,
166
]
],
"normalized": []
},
{
"id": "10423406_T5",
"type": "Protein",
"text": [
"interleukin (IL)-8"
],
"offsets": [
[
181,
199
]
],
"normalized": []
},
{
"id": "10423406_T6",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
227,
230
]
],
"normalized": []
},
{
"id": "10423406_T7",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
334,
338
]
],
"normalized": []
},
{
"id": "10423406_T8",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
365,
368
]
],
"normalized": []
},
{
"id": "10423406_T9",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
412,
416
]
],
"normalized": []
},
{
"id": "10423406_T10",
"type": "Protein",
"text": [
"eosinophil cationic protein"
],
"offsets": [
[
500,
527
]
],
"normalized": []
},
{
"id": "10423406_T11",
"type": "Protein",
"text": [
"eosinophil peroxidase"
],
"offsets": [
[
564,
585
]
],
"normalized": []
},
{
"id": "10423406_T12",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
626,
630
]
],
"normalized": []
},
{
"id": "10423406_T13",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
643,
646
]
],
"normalized": []
},
{
"id": "10423406_T14",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
678,
682
]
],
"normalized": []
},
{
"id": "10423406_T15",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
816,
819
]
],
"normalized": []
},
{
"id": "10423406_T16",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
1027,
1030
]
],
"normalized": []
},
{
"id": "10423406_T17",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1058,
1062
]
],
"normalized": []
},
{
"id": "10423406_T18",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
1069,
1072
]
],
"normalized": []
},
{
"id": "10423406_T19",
"type": "Protein",
"text": [
"macrophage inflammatory protein (MIP)-1alpha"
],
"offsets": [
[
1118,
1162
]
],
"normalized": []
},
{
"id": "10423406_T20",
"type": "Protein",
"text": [
"MIP-1beta"
],
"offsets": [
[
1167,
1176
]
],
"normalized": []
},
{
"id": "10423406_T21",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
1262,
1265
]
],
"normalized": []
},
{
"id": "10423406_T22",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1346,
1350
]
],
"normalized": []
},
{
"id": "10423406_T23",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1404,
1408
]
],
"normalized": []
},
{
"id": "10423406_T24",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
1420,
1423
]
],
"normalized": []
},
{
"id": "10423406_T25",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
1508,
1511
]
],
"normalized": []
},
{
"id": "10423406_T26",
"type": "Protein",
"text": [
"IL-8"
],
"offsets": [
[
1531,
1535
]
],
"normalized": []
}
] | [
{
"id": "10423406_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
40,
50
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T1"
}
]
},
{
"id": "10423406_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
171,
180
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E3"
},
{
"role": "Cause",
"ref_id": "10423406_T4"
}
]
},
{
"id": "10423406_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
200,
210
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T5"
}
]
},
{
"id": "10423406_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
280,
290
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E5"
},
{
"role": "Cause",
"ref_id": "10423406_T6"
}
]
},
{
"id": "10423406_E5",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
295,
302
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T7"
}
]
},
{
"id": "10423406_E6",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
417,
424
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T9"
}
]
},
{
"id": "10423406_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
425,
434
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E6"
},
{
"role": "Cause",
"ref_id": "10423406_T8"
}
]
},
{
"id": "10423406_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
631,
641
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T12"
}
]
},
{
"id": "10423406_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
647,
657
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E10"
},
{
"role": "Cause",
"ref_id": "10423406_T13"
}
]
},
{
"id": "10423406_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
665,
674
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T14"
}
]
},
{
"id": "10423406_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocked"
],
"offsets": [
[
746,
753
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E9"
}
]
},
{
"id": "10423406_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"prolonged the stability"
],
"offsets": [
[
1031,
1054
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T17"
}
]
},
{
"id": "10423406_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
1096,
1105
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T20"
},
{
"role": "Cause",
"ref_id": "10423406_T18"
}
]
},
{
"id": "10423406_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
1096,
1105
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T19"
},
{
"role": "Cause",
"ref_id": "10423406_T18"
}
]
},
{
"id": "10423406_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
1190,
1199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E17"
},
{
"role": "Cause",
"ref_id": "10423406_T18"
}
]
},
{
"id": "10423406_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
1190,
1199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E18"
},
{
"role": "Cause",
"ref_id": "10423406_T18"
}
]
},
{
"id": "10423406_E17",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
1204,
1211
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T19"
}
]
},
{
"id": "10423406_E18",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
1204,
1211
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T20"
}
]
},
{
"id": "10423406_E19",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
1351,
1358
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T22"
}
]
},
{
"id": "10423406_E20",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
1409,
1416
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T23"
}
]
},
{
"id": "10423406_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1512,
1519
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_E22"
},
{
"role": "Cause",
"ref_id": "10423406_T25"
}
]
},
{
"id": "10423406_E22",
"type": "Localization",
"trigger": {
"text": [
"release"
],
"offsets": [
[
1520,
1527
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10423406_T26"
}
]
}
] | [
{
"id": "10423406_1",
"entity_ids": [
"10423406_T3",
"10423406_T4"
]
}
] | [] |
9081693 | 9081693 | [
{
"id": "9081693__text",
"type": "abstract",
"text": [
"Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NF-kappa B/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression. \nTissue factor (TF) expression by peripheral blood monocytes during sepsis initiates intravascular thrombosis. Bacterial lipopolysaccharide (LPS) rapidly induces TF gene transcription in monocytes. The human TF promoter contains binding sites for the transcription factors AP-1, c-Rel/p65, Egr-1, and Sp1. NF-kappa B/Rel proteins have been shown to physically interact with both AP-1 and Sp1 proteins. In this study, we investigated the role of these transcription factors in uninduced and LPS-induced TF gene expression in human monocytic THP-1 cells. Deletional analysis indicated that five Sp1 sites mediated basal expression in uninduced cells. The two AP-1 sites bound c-Fos/c-Jun heterodimers in both unstimulated and LPS-stimulated cells. Maximal LPS induction of the TF promoter required the two AP-1 sites and the kappa B site within the LPS response element. Disruption of the conserved spacing between the proximal AP-1 site and the kappa B site abolished LPS induction. Replacement of the two AP-1 sites with intrinsically bent DNA partially restored LPS induction, suggesting an additional structural role for the AP-1 sites. Synergistic transactivation of the LPS response element in Drosophila Schneider cells by coexpression of c-Fos, c-Jun, c-Rel, and p65 or c-Jun and p65 required the transactivation domains of c-Jun and p65. These data indicated that c-Fos/c-Jun, c-Rel/p65, and Sp1 regulate TF gene expression in human monocytic cells. "
],
"offsets": [
[
0,
1623
]
]
}
] | [
{
"id": "9081693_T1",
"type": "Protein",
"text": [
"tissue factor"
],
"offsets": [
[
18,
31
]
],
"normalized": []
},
{
"id": "9081693_T2",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
97,
100
]
],
"normalized": []
},
{
"id": "9081693_T3",
"type": "Protein",
"text": [
"Tissue factor"
],
"offsets": [
[
167,
180
]
],
"normalized": []
},
{
"id": "9081693_T4",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
182,
184
]
],
"normalized": []
},
{
"id": "9081693_T5",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
328,
330
]
],
"normalized": []
},
{
"id": "9081693_T6",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
374,
376
]
],
"normalized": []
},
{
"id": "9081693_T7",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
445,
450
]
],
"normalized": []
},
{
"id": "9081693_T8",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
451,
454
]
],
"normalized": []
},
{
"id": "9081693_T9",
"type": "Protein",
"text": [
"Egr-1"
],
"offsets": [
[
456,
461
]
],
"normalized": []
},
{
"id": "9081693_T10",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
467,
470
]
],
"normalized": []
},
{
"id": "9081693_T11",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
554,
557
]
],
"normalized": []
},
{
"id": "9081693_T12",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
668,
670
]
],
"normalized": []
},
{
"id": "9081693_T13",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
759,
762
]
],
"normalized": []
},
{
"id": "9081693_T14",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
840,
845
]
],
"normalized": []
},
{
"id": "9081693_T15",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
846,
851
]
],
"normalized": []
},
{
"id": "9081693_T16",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
941,
943
]
],
"normalized": []
},
{
"id": "9081693_T17",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
1410,
1415
]
],
"normalized": []
},
{
"id": "9081693_T18",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
1417,
1422
]
],
"normalized": []
},
{
"id": "9081693_T19",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1424,
1429
]
],
"normalized": []
},
{
"id": "9081693_T20",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1435,
1438
]
],
"normalized": []
},
{
"id": "9081693_T21",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
1442,
1447
]
],
"normalized": []
},
{
"id": "9081693_T22",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1452,
1455
]
],
"normalized": []
},
{
"id": "9081693_T23",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
1496,
1501
]
],
"normalized": []
},
{
"id": "9081693_T24",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1506,
1509
]
],
"normalized": []
},
{
"id": "9081693_T25",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
1537,
1542
]
],
"normalized": []
},
{
"id": "9081693_T26",
"type": "Protein",
"text": [
"c-Jun"
],
"offsets": [
[
1543,
1548
]
],
"normalized": []
},
{
"id": "9081693_T27",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1550,
1555
]
],
"normalized": []
},
{
"id": "9081693_T28",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1556,
1559
]
],
"normalized": []
},
{
"id": "9081693_T29",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1565,
1568
]
],
"normalized": []
},
{
"id": "9081693_T30",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1578,
1580
]
],
"normalized": []
},
{
"id": "9081693_T43",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
944,
952
]
],
"normalized": []
}
] | [
{
"id": "9081693_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T1"
}
]
},
{
"id": "9081693_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
186,
196
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T4"
}
]
},
{
"id": "9081693_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
320,
327
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E4"
}
]
},
{
"id": "9081693_E4",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
336,
349
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T5"
}
]
},
{
"id": "9081693_E5",
"type": "Binding",
"trigger": {
"text": [
"interact"
],
"offsets": [
[
526,
534
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T11"
}
]
},
{
"id": "9081693_E6",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E17"
},
{
"role": "Cause",
"ref_id": "9081693_T7"
}
]
},
{
"id": "9081693_E7",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E16"
},
{
"role": "Cause",
"ref_id": "9081693_T7"
}
]
},
{
"id": "9081693_E8",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E16"
},
{
"role": "Cause",
"ref_id": "9081693_T8"
}
]
},
{
"id": "9081693_E9",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E17"
},
{
"role": "Cause",
"ref_id": "9081693_T8"
}
]
},
{
"id": "9081693_E10",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E16"
}
]
},
{
"id": "9081693_E11",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E17"
},
{
"role": "Cause",
"ref_id": "9081693_T9"
}
]
},
{
"id": "9081693_E12",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E16"
},
{
"role": "Cause",
"ref_id": "9081693_T9"
}
]
},
{
"id": "9081693_E13",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E17"
}
]
},
{
"id": "9081693_E14",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E16"
},
{
"role": "Cause",
"ref_id": "9081693_T10"
}
]
},
{
"id": "9081693_E15",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
603,
607
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E17"
},
{
"role": "Cause",
"ref_id": "9081693_T10"
}
]
},
{
"id": "9081693_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
660,
667
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E17"
}
]
},
{
"id": "9081693_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
676,
686
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T12"
}
]
},
{
"id": "9081693_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
769,
777
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E19"
}
]
},
{
"id": "9081693_E19",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
784,
794
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T12"
}
]
},
{
"id": "9081693_E20",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
834,
839
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T14"
}
]
},
{
"id": "9081693_E21",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
834,
839
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T15"
}
]
},
{
"id": "9081693_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
924,
933
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T16"
},
{
"role": "Site",
"ref_id": "9081693_T43"
}
]
},
{
"id": "9081693_E23",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
953,
961
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E22"
}
]
},
{
"id": "9081693_E24",
"type": "Negative_regulation",
"trigger": {
"text": [
"abolished"
],
"offsets": [
[
1123,
1132
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E25"
}
]
},
{
"id": "9081693_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1137,
1146
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T16"
},
{
"role": "Site",
"ref_id": "9081693_T43"
}
]
},
{
"id": "9081693_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"restored"
],
"offsets": [
[
1220,
1228
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E27"
}
]
},
{
"id": "9081693_E27",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1233,
1242
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T16"
},
{
"role": "Site",
"ref_id": "9081693_T43"
}
]
},
{
"id": "9081693_E28",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1394,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T17"
}
]
},
{
"id": "9081693_E29",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1394,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T20"
}
]
},
{
"id": "9081693_E30",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1394,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T19"
}
]
},
{
"id": "9081693_E31",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1394,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T18"
}
]
},
{
"id": "9081693_E32",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1394,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T21"
}
]
},
{
"id": "9081693_E33",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1394,
1406
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T22"
}
]
},
{
"id": "9081693_E34",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
1569,
1577
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E39"
},
{
"role": "Cause",
"ref_id": "9081693_T26"
}
]
},
{
"id": "9081693_E35",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
1569,
1577
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E39"
},
{
"role": "Cause",
"ref_id": "9081693_T28"
}
]
},
{
"id": "9081693_E36",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
1569,
1577
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E39"
},
{
"role": "Cause",
"ref_id": "9081693_T25"
}
]
},
{
"id": "9081693_E37",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
1569,
1577
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E39"
},
{
"role": "Cause",
"ref_id": "9081693_T29"
}
]
},
{
"id": "9081693_E38",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
1569,
1577
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_E39"
},
{
"role": "Cause",
"ref_id": "9081693_T27"
}
]
},
{
"id": "9081693_E39",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1586,
1596
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9081693_T30"
}
]
}
] | [
{
"id": "9081693_1",
"entity_ids": [
"9081693_T3",
"9081693_T4"
]
}
] | [] |
1620119 | 1620119 | [
{
"id": "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": "1620119_T1",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "1620119_T2",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
218,
222
]
],
"normalized": []
},
{
"id": "1620119_T3",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
290,
294
]
],
"normalized": []
},
{
"id": "1620119_T4",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
422,
426
]
],
"normalized": []
},
{
"id": "1620119_T5",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
592,
596
]
],
"normalized": []
},
{
"id": "1620119_T6",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
818,
822
]
],
"normalized": []
},
{
"id": "1620119_T7",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
834,
838
]
],
"normalized": []
},
{
"id": "1620119_T8",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
934,
938
]
],
"normalized": []
},
{
"id": "1620119_T9",
"type": "Protein",
"text": [
"Oct1"
],
"offsets": [
[
1045,
1049
]
],
"normalized": []
},
{
"id": "1620119_T10",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
1201,
1205
]
],
"normalized": []
}
] | [
{
"id": "1620119_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
159,
169
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1620119_T2"
}
]
},
{
"id": "1620119_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
295,
305
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1620119_T3"
}
]
},
{
"id": "1620119_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"generated"
],
"offsets": [
[
436,
445
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1620119_T4"
}
]
}
] | [] | [] |
1537389 | 1537389 | [
{
"id": "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": "1537389_T1",
"type": "Protein",
"text": [
"Interleukin 6"
],
"offsets": [
[
0,
13
]
],
"normalized": []
},
{
"id": "1537389_T2",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
108,
113
]
],
"normalized": []
},
{
"id": "1537389_T3",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
146,
151
]
],
"normalized": []
},
{
"id": "1537389_T4",
"type": "Protein",
"text": [
"interleukin (IL) 6"
],
"offsets": [
[
155,
173
]
],
"normalized": []
},
{
"id": "1537389_T5",
"type": "Protein",
"text": [
"IL 6"
],
"offsets": [
[
251,
255
]
],
"normalized": []
},
{
"id": "1537389_T6",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
301,
306
]
],
"normalized": []
},
{
"id": "1537389_T7",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
450,
455
]
],
"normalized": []
},
{
"id": "1537389_T8",
"type": "Protein",
"text": [
"IL 6"
],
"offsets": [
[
480,
484
]
],
"normalized": []
},
{
"id": "1537389_T9",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
647,
652
]
],
"normalized": []
},
{
"id": "1537389_T10",
"type": "Protein",
"text": [
"IL 6"
],
"offsets": [
[
668,
672
]
],
"normalized": []
}
] | [
{
"id": "1537389_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
286,
297
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1537389_E2"
}
]
},
{
"id": "1537389_E2",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
318,
328
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1537389_T6"
}
]
},
{
"id": "1537389_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"appeared"
],
"offsets": [
[
341,
349
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1537389_E1"
}
]
},
{
"id": "1537389_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"returned"
],
"offsets": [
[
368,
376
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1537389_E1"
}
]
},
{
"id": "1537389_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
633,
643
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1537389_T9"
}
]
}
] | [] | [] |
9201242 | 9201242 | [
{
"id": "9201242__text",
"type": "abstract",
"text": [
"Effect of adenovirus 2 on cellular gene activation in blood-derived monocytes and macrophages. \nWe have investigated the effect of adenovirus 2 (Ad2) infection on human monocytes and monocyte-derived macrophages with regard to expression of TNF-alpha and IL-1 beta. In monocytes, the virus was bound to the surface without being internalized. On the other hand, Ad2 was internalized by macrophages. No virus replication and no transcription of the Ad2 early genes was observed in either of the cells. Ad2 infection induced transient increase in the mRNA levels for TNF-alpha and IL-1 beta in both monocytes and in macrophages, although the kinetics of the transcription was slightly different. The production of both cytokines, measured by ELISA tests, was enhanced in monocytes. In macrophages, a slight enhancement of TNF-alpha production was seen, whereas IL-1 beta was not detected. The data indicate that cellular genes might be activated by Ad2 virus infection in nonpermissive cells where no viral gene products could be detected. "
],
"offsets": [
[
0,
1038
]
]
}
] | [
{
"id": "9201242_T1",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
241,
250
]
],
"normalized": []
},
{
"id": "9201242_T2",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
255,
264
]
],
"normalized": []
},
{
"id": "9201242_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
565,
574
]
],
"normalized": []
},
{
"id": "9201242_T4",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
579,
588
]
],
"normalized": []
},
{
"id": "9201242_T5",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
820,
829
]
],
"normalized": []
},
{
"id": "9201242_T6",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
859,
868
]
],
"normalized": []
}
] | [
{
"id": "9201242_E1",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
121,
127
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E4"
}
]
},
{
"id": "9201242_E2",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
121,
127
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E3"
}
]
},
{
"id": "9201242_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
227,
237
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T1"
}
]
},
{
"id": "9201242_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
227,
237
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T2"
}
]
},
{
"id": "9201242_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
515,
522
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E8"
}
]
},
{
"id": "9201242_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
515,
522
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E7"
}
]
},
{
"id": "9201242_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
533,
541
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E9"
}
]
},
{
"id": "9201242_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
533,
541
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E10"
}
]
},
{
"id": "9201242_E9",
"type": "Transcription",
"trigger": {
"text": [
"mRNA levels"
],
"offsets": [
[
549,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T4"
}
]
},
{
"id": "9201242_E10",
"type": "Transcription",
"trigger": {
"text": [
"mRNA levels"
],
"offsets": [
[
549,
560
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T3"
}
]
},
{
"id": "9201242_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
698,
708
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T4"
}
]
},
{
"id": "9201242_E12",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
698,
708
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T3"
}
]
},
{
"id": "9201242_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
757,
765
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E12"
}
]
},
{
"id": "9201242_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
757,
765
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E11"
}
]
},
{
"id": "9201242_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhancement"
],
"offsets": [
[
805,
816
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_E16"
}
]
},
{
"id": "9201242_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
830,
840
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T5"
}
]
},
{
"id": "9201242_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
877,
885
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9201242_T6"
}
]
}
] | [] | [] |
9013959 | 9013959 | [
{
"id": "9013959__text",
"type": "abstract",
"text": [
"Differential interaction of nuclear factors with the PRE-I enhancer element of the human IL-4 promoter in different T cell subsets. \nThe immunomodulatory cytokine IL-4 affects cells of most hemopoietic lineages. IL-4 is secreted by activated Th2 but not Th1 cells and plays a major role in the immune response by modulating the differentiation of naive Th cells toward the Th2 phenotype. We have previously identified an enhancer element, PRE-I, that is essential for the function of the human IL-4 promoter. To investigate the mechanisms responsible for tissue-specific expression of the IL-4 gene, we analyzed nuclear factors binding to the PRE-I site and compared the binding activities of these factors to the IL-4 promoter of Th1 and Th2 cells. We show that PRE-I interacts with PMA- and PMA/ionomycin-inducible, cyclosporin A-sensitive nuclear factors. Using anti-C/EBPbeta (NF-IL6), anti-C/EBPdelta (NF-IL6beta), anti-NF-ATc, anti-NF-ATp, anti-Fos, and anti-Jun Abs we demonstrate that the previously identified PRE-I binding factor POS-1 is composed of different transcription factors in different Th cell subsets. In the IL-4-producing Th0-like human Jurkat and mouse EL-4 cells, POS-1 (designated POS-1a) contains NF-IL6beta and Jun. In the mouse Th2 D10 cells and in the human Th2 clones, POS-1 (designated POS-1b) contains NF-IL6beta, Jun, and NF-ATc/p. In contrast, POS-1 was not found in nuclear extracts of human Th1 clones. These findings suggest that PRE-I may play a role in the differential regulation of IL-4 gene expression levels. "
],
"offsets": [
[
0,
1553
]
]
}
] | [
{
"id": "9013959_T1",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
89,
93
]
],
"normalized": []
},
{
"id": "9013959_T2",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
163,
167
]
],
"normalized": []
},
{
"id": "9013959_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
212,
216
]
],
"normalized": []
},
{
"id": "9013959_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
494,
498
]
],
"normalized": []
},
{
"id": "9013959_T5",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
589,
593
]
],
"normalized": []
},
{
"id": "9013959_T6",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
714,
718
]
],
"normalized": []
},
{
"id": "9013959_T7",
"type": "Protein",
"text": [
"C/EBPbeta"
],
"offsets": [
[
870,
879
]
],
"normalized": []
},
{
"id": "9013959_T8",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
881,
887
]
],
"normalized": []
},
{
"id": "9013959_T9",
"type": "Protein",
"text": [
"C/EBPdelta"
],
"offsets": [
[
895,
905
]
],
"normalized": []
},
{
"id": "9013959_T10",
"type": "Protein",
"text": [
"NF-IL6beta"
],
"offsets": [
[
907,
917
]
],
"normalized": []
},
{
"id": "9013959_T11",
"type": "Protein",
"text": [
"NF-ATc"
],
"offsets": [
[
925,
931
]
],
"normalized": []
},
{
"id": "9013959_T12",
"type": "Protein",
"text": [
"NF-ATp"
],
"offsets": [
[
938,
944
]
],
"normalized": []
},
{
"id": "9013959_T13",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1130,
1134
]
],
"normalized": []
},
{
"id": "9013959_T14",
"type": "Protein",
"text": [
"NF-IL6beta"
],
"offsets": [
[
1224,
1234
]
],
"normalized": []
},
{
"id": "9013959_T15",
"type": "Protein",
"text": [
"NF-IL6beta"
],
"offsets": [
[
1335,
1345
]
],
"normalized": []
},
{
"id": "9013959_T16",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1524,
1528
]
],
"normalized": []
}
] | [
{
"id": "9013959_E1",
"type": "Localization",
"trigger": {
"text": [
"secreted"
],
"offsets": [
[
220,
228
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_T3"
}
]
},
{
"id": "9013959_E2",
"type": "Regulation",
"trigger": {
"text": [
"responsible"
],
"offsets": [
[
539,
550
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_E3"
}
]
},
{
"id": "9013959_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
571,
581
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_T5"
}
]
},
{
"id": "9013959_E4",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
671,
678
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_T6"
}
]
},
{
"id": "9013959_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"producing"
],
"offsets": [
[
1135,
1144
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_T13"
}
]
},
{
"id": "9013959_E6",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
1485,
1489
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_E7"
}
]
},
{
"id": "9013959_E7",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1510,
1520
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_E8"
}
]
},
{
"id": "9013959_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1534,
1544
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9013959_T16"
}
]
}
] | [
{
"id": "9013959_1",
"entity_ids": [
"9013959_T9",
"9013959_T10"
]
},
{
"id": "9013959_2",
"entity_ids": [
"9013959_T7",
"9013959_T8"
]
}
] | [] |
8011280 | 8011280 | [
{
"id": "8011280__text",
"type": "abstract",
"text": [
"Function and activation of NF-kappa B in the immune system. \nNF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes. "
],
"offsets": [
[
0,
1860
]
]
}
] | [
{
"id": "8011280_T1",
"type": "Protein",
"text": [
"Bcl-3"
],
"offsets": [
[
1058,
1063
]
],
"normalized": []
}
] | [] | [] | [] |