E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation

Mary C. Thomas, Cheng Ming Chiang

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

The mechanism employed by DNA tumor viruses to inhibit p53-dependent transcription from chromatin is poorly understood. Here, we use in vitro-reconstituted chromatin and UV-irradiated cells to define the mechanism of human papillomavirus E6 oncoprotein in repressing p53-dependent transcription. We demonstrate that E6 does not prevent p53 or p300 recruitment to the chromatin but inhibits p300-mediated acetylation on p53 and nucleosomal core histones. This suppression of protein acetylation requires the E6-interacting regions of p300. Moreover, E6 mutants unable to interact with p53 or p300, but not deficient in inducing p53 degradation, fail to inhibit p53-mediated activation, indicating that a p53-E6-p300-containing protein complex is critical for repressing p53-targeted gene activation. That E6 acts as a molecular switch converting p53-p300 from an activating complex to a repressing entity on the chromatin, which occurs independently of E6AP-mediated protein degradation pathway, may represent a general mechanism for gene regulation.

Original languageEnglish (US)
Pages (from-to)251-264
Number of pages14
JournalMolecular cell
Volume17
Issue number2
DOIs
StatePublished - Jan 21 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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