Functional Analysis of p53 Acetylation in Prostate Tumor Suppression

Abstract

The tumor suppressor p53 is stabilized and activated in response to cellular stress through post translational modifications including acetylation. p300/CBP-mediated acetylation of p53 is negatively regulated by MDM2. We show that MDM2 can promote p53 deacetylation by recruiting a complex containing HDAC1. The HDAC1 complex binds MDM2 in a p53-independent manner and deacetylates p53 at all known acetylated lysines in vivo. Ectopic expression of a dominant negative HDAC1 mutant restores p53 acetylation in the presence of MDM2, whereas wild-type HDAC1 and MDM2 deacetylate p53 synergistically. Fibroblasts over-expressing a dominant negative HDAC1 mutant display enhanced DNA damage-induced p53 acetylation, increased levels of p53, and a more pronounced induction of p21 and MDM2.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA418266

Entities

People

  • Tso-pang Yao

Organizations

  • Duke University Hospital

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Biology
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Degradation
  • Electronic Mail
  • Enzyme Inhibitors
  • Fibroblasts
  • Functional Analysis
  • Mass Spectrometry
  • Materials
  • Prostate
  • Proteins
  • Recruiting

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics