p53 Oligomerization Is Essential for Its C-terminal Lysine Acetylation*

Acetylation of multiple lysine residues in the p53 plays critical roles in the protein stability and transcriptional activity of p53. To better understand how p53 acetylation is regulated, we generated a number of p53 mutants and examined acetylation of each mutant in transfected cells. We found that p53 mutants that are defective in tetramer formation are also defective in C-terminal lysine residue acetylation. Consistently, we found that several cancer-derived p53 mutants that bear mutations in the tetramerization domain cannot form oligomers and are defective in C-terminal lysine acetylation, and these mutants are inactive in p21 transactivation. We demonstrated that the acetyltransferase p300 interacts with and promotes acetylation of wild-type p53 but not with any of the artificially generated or human cancer-derived p53 mutants that are defective in oligomerization. These results, combined with a computer-aided crystal structure analysis, suggest a model in which p53 oligomerization precedes its acetylation by providing docking sites for acetyltransferases.

• Publication year

  2009

• Venue

  Journal of Biological Chemistry

• Publication date

  2009-02-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M805696200PMID 19106109PMCID PMC2643511
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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