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• W2327261337 abstract "Serum-stimulation of quiescent mouse fibroblasts results in transcriptional activation of tissue factor (TF), the cellular initiator of blood coagulation. This requires the rapid entry of c-Fos into specific AP-1 DNA-binding complexes and can be strongly inhibited by the adenovirus EIA 12S gene product. In this study, we utilized a panel of E1A mutants deficient in cellular protein binding to analyse the molecular basis for EIA inhibition of a minimal, c-Fos-dependent TF promoter/ reporter construct in mouse AKR-2B fibroblasts. Mutations which impaired binding of the retinoblastoma tumor suppressor protein family members pRB, p107, and p130 relieved E1A-mediated inhibition of transcription in response to serum-stimulation or c-Fos overexpression. Inhibition was restricted to the G0 to G1 transition, consistent with the specificity of E1A for hypophosphorylated forms of RB proteins. Although E1A mutants deficient in CBP/p300 binding retained the ability to inhibit TF transcription, deletion of the amino-terminal portion of the CBP/p300 interaction domain was required to permit rescue of TF promoter activity by coexpression of pRB. Moreover, ectopic p107 could effectively substitute for pRB in relieving E1A-mediated repression. In primary mouse embryo fibroblasts, activity of the minimal AP-1-dependent TF promoter was suppressed in Rb(-/-) cells compared to parallel Rb(+/-) and Rb(+/+) transfectants. Ectopic expression of either pRB or p107 markedly enhanced TF promoter activity in Rb(-/-) fibroblasts. Collectively, these data imply that pRB and p107 can cooperate with c-Fos to activate TF gene transcription in fibroblasts and suggest a requirement for another, as yet unidentified, E1A-binding protein." @default.
• W2327261337 created "2016-06-24" @default.
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• W2327261337 date "2000-07-01" @default.
• W2327261337 modified "2023-09-23" @default.
• W2327261337 title "The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts" @default.
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• W2327261337 doi "https://doi.org/10.1038/sj.onc.1203675" @default.
• W2327261337 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10918592" @default.
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