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Transcription factor TFIID is a direct functional target of the adenovirus E1A transcription-repression domain

C Z Song1, P M Loewenstein, K Toth

  • 1Institute for Molecular Virology, St. Louis University School of Medicine, MO 63110, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 24, 1995
PubMed

Insights

Adenovirus E1A oncoprotein represses gene transcription by targeting the TATA-box binding protein (TBP). This interaction explains how E1A controls cell growth and transformation, offering insights into viral oncogenesis.

Area of Science:

  • Molecular Biology
  • Virology
  • Gene Regulation

Background:

  • Adenovirus E1A oncoprotein modulates cellular gene expression, impacting cell growth, proliferation, and differentiation.
  • The precise mechanism of E1A-mediated transcription repression has remained unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism underlying adenovirus E1A's transcription repression function.
  • To identify the cellular target of the E1A repression domain.

Main Methods:

  • In vitro transcription assays using TATA-containing core promoters.
  • Reconstitution experiments with purified TATA-box binding protein (TBP).
  • In vitro interaction assays between E1A and TBP.

Main Results:

  • The E1A N-terminal 80 amino acids (E1A-(1-80)) repressed basal transcription from TATA-containing promoters.
  • TBP fully reversed E1A repression in vitro.
  • TBP restored transcriptional activity in nuclear extracts depleted of E1A-binding proteins.
  • Direct and specific interaction was observed between the E1A N-terminal repression domain and TBP.

Conclusions:

  • The TATA-box binding protein (TBP) is a direct cellular target of the adenovirus E1A oncoprotein's repression function.
  • This interaction with TBP explains E1A's ability to repress genes lacking common upstream elements.
  • Findings provide a mechanistic basis for E1A's role in cell growth dysregulation and viral transformation.

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