The transcription factor E2F-1 modulates TGF-β1 RNA expression in glial cells
| العنوان: | The transcription factor E2F-1 modulates TGF-β1 RNA expression in glial cells |
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| المؤلفون: | Prakash Thatikunta, Ganesh V. Raj, Kamel Khalili, Shohreh Amini, Mondira Kundu |
| المصدر: | Oncogene. 14:2959-2969 |
| بيانات النشر: | Springer Science and Business Media LLC, 1997. |
| سنة النشر: | 1997 |
| مصطلحات موضوعية: | Cancer Research, Transcription, Genetic, Antigens, Polyomavirus Transforming, Molecular Sequence Data, Cell Cycle Proteins, Regulatory Sequences, Nucleic Acid, Biology, Retinoblastoma Protein, Sp3 transcription factor, Transforming Growth Factor beta, Gene expression, Tumor Cells, Cultured, Genetics, Humans, E2F1, RNA, Neoplasm, Promoter Regions, Genetic, E2F, Molecular Biology, Transcription factor, Base Sequence, Transforming growth factor beta, E2F Transcription Factors, Cell biology, DNA-Binding Proteins, Regulatory sequence, Astrocytes, biology.protein, Cancer research, biological phenomena, cell phenomena, and immunity, Carrier Proteins, Glioblastoma, Transcription Factor DP1, E2F1 Transcription Factor, Retinoblastoma-Binding Protein 1, Transcription Factors |
| الوصف: | The cell type specificity of the regulation of expression of the potent growth inhibitory cytokine transforming growth factor-beta (TGF-beta), prompted our analyses of the regulation of TGF-beta1 gene expression in glial cells by viral and cellular oncoproteins. We have shown that SV40 T-antigen diminished TGF-beta1 expression in glial cells and this repression was dependent on the ability of T-antigen to interact with the tumor suppressor protein, pRb, and two structurally related proteins, p107 and p130. The cellular transcription factor E2F-1, which is a downstream effector of T-antigen, was unable to influence expression from the TGF-beta1 promoter by itself. Interestingly, E2F-1 could overcome viral T-antigen-mediated repression of the TGF-beta1 promoter, suggesting potential feedback loop between TGF-beta and E2F in virally transformed glial cells. Using deletion analyses, we have mapped two E2F-1-responsive regions on the TGF-beta1 promoter: a T-antigen-dependent negative regulatory sequence (TdNRS) between -323 and -175, and a T-antigen-independent positive regulatory sequence (TiPRS) between -34 and +10 on the TGF-beta1 promoter. Further examination of TiPRS revealed the presence of a functional E2F binding site. Interestingly, the amino terminus of E2F-1 was required for its activation of TGF-beta1 expression, as mutations in that domain abolished the ability of E2F-1 to increase TGF-beta1 expression. These data suggest that yet-uncharacterized interaction between the amino terminus of E2F-1 and cellular proteins regulates TGF-beta1 expression. The mechanism for E2F-1-mediated T-antigen-dependent regulation of TGF-beta1 expression from TdNRS awaits further characterization. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::032386f174d8121d86184434f79cf86aTest https://doi.org/10.1038/sj.onc.1201129Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....032386f174d8121d86184434f79cf86a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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