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 Citations (Scopus)

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 - 1997

Fingerprint

E2F1 Transcription Factor
Neuroglia
Transforming Growth Factor beta
RNA
Viral Tumor Antigens
T Independent Antigens
Polyomavirus Transforming Antigens
Tumor Suppressor Proteins
Oncogene Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The transcription factor E2F-1 modulates TGF-β1 RNA expression in glial cells. / Thatikunta, Prakash; Raj, Ganesh V.; Kundu, Mondira; Khalili, Kamel; Amini, Shohreh.

In: Oncogene, Vol. 14, No. 24, 1997, p. 2959-2969.

Research output: Contribution to journalArticle

Thatikunta, P, Raj, GV, Kundu, M, Khalili, K & Amini, S 1997, 'The transcription factor E2F-1 modulates TGF-β1 RNA expression in glial cells', Oncogene, vol. 14, no. 24, pp. 2959-2969. https://doi.org/10.1038/sj.onc.1201129
Thatikunta, Prakash ; Raj, Ganesh V. ; Kundu, Mondira ; Khalili, Kamel ; Amini, Shohreh. / The transcription factor E2F-1 modulates TGF-β1 RNA expression in glial cells. In: Oncogene. 1997 ; Vol. 14, No. 24. pp. 2959-2969.
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