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E6 Oncoprotein Represses p53-Dependent Gene Activation via Inhibition of Protein Acetylation Independently of Inducing p53 Degradation

Thomas, Mary C., Chiang, Cheng-Ming·2005·Molecular Cell
DOI 10.1016/j.molcel.2004.12.016
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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.

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Metadata

Authors
Thomas, M. C., & Chiang, C.-M.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2005-01
Volume
17
Issue
2
Pages
251-264
ISSN
1097-2765
DOI
10.1016/j.molcel.2004.12.016
Cited by
178
References
2
Language
en
Licence
Funders
National Institutes of Health

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CoChat. (2026). Citation check: E6 Oncoprotein Represses p53-Dependent Gene Activation via Inhibition of Protein Acetylation Independently of Inducing p53 Degradation. https://app.cochat.ai/papers/10.1016/j.molcel.2004.12.016
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Thomas, M. C., & Chiang, C.-M. (2005). E6 Oncoprotein Represses p53-Dependent Gene Activation via Inhibition of Protein Acetylation Independently of Inducing p53 Degradation. Molecular Cell. https://doi.org/10.1016/j.molcel.2004.12.016