The transcription factor E2F-1 modulates TGF-β1 RNA expression in glial cells

Prakash Thatikunta, Ganesh V. Raj, Mondira Kundu, Kamel Khalili, Shohreh Amini

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The cell type specificity of the regulation of expression of the potent growth inhibitory cytokine transforming growth factor-beta (TGF-β), prompted our analyses of the regulation of TGF-β1 gene expression in glial cells by viral and cellular oncoproteins. We have shown that SV40 T-antigen diminished TGF-β1 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-β1 promoter by itself. Interestingly, E2F-1 could overcome viral T-antigen-mediated repression of the TGF-β1 promoter, suggesting potential feedback loop between TGF-β and E2F in virally transformed glial cells. Using deletion analyses, we have mapped two E2F-1-responsive regions on the TGF-β1 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-β1 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-β1 expression, as mutations in that domain abolished the ability of E2F-1 to increase TGF-β1 expression. These data suggest that yet-uncharacterized interaction between the amino terminus of E2F-1 and cellular proteins regulates TGF-β1 expression. The mechanism for E2F-1-mediated T-antigen-dependent regulation of TGF-β1 expression from TdNRS awaits further characterization.

Original languageEnglish (US)
Pages (from-to)2959-2969
Number of pages11
JournalOncogene
Volume14
Issue number24
DOIs
StatePublished - Aug 9 1997

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Keywords

  • Central nervous system
  • E2F1
  • Gene expression
  • Oncoproteins
  • TGF-β1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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