p53 acetylation is crucial for its transcription-independent proapoptotic functions

Hirohito Yamaguchi, Nicholas T Woods, Landon G. Piluso, Heng Huan Lee, Jiandong Chen, Kapil N. Bhalla, Alvaro Monteiro, Xuan Liu, Mien Chie Hung, Hong Gang Wang

Research output: Contribution to journalArticle

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Abstract

Acetylation of p53 at carboxyl-terminal lysine residues enhances its transcriptional activity associated with cell cycle arrest and apoptosis. Here we demonstrate that p53 acetylation at Lys-320/Lys-373/ Lys-382 is also required for its transcription-independent functions in BAX activation, reactive oxygen species production, and apoptosis in response to the histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid and LAQ824. Knock-out of p53 markedly reduced HDACiinduced apoptosis. Unexpectedly, expression of transactivation-deficient p53 variants sensitized p53-null cells to HDACimediated BAX-dependent apoptosis, whereas knockdown of endogenous mutant p53 in cancer cells reduced HDACi-mediated cytotoxicity. Evaluation of the mechanisms controlling this response led to the discovery of a novel interaction between p53 and Ku70. The association between these two proteins was acetylation-independent, but acetylation of p53 could prevent and disrupt the Ku70-BAX complex and enhance apoptosis. These results suggest a new mechanism of acetylated p53 transcription-independent regulation of apoptosis.

Original languageEnglish (US)
Pages (from-to)11171-11183
Number of pages13
JournalJournal of Biological Chemistry
Volume284
Issue number17
DOIs
StatePublished - Apr 24 2009

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Acetylation
Transcription
Apoptosis
Histone Deacetylase Inhibitors
Cells
Null Lymphocytes
Cytotoxicity
Cell Cycle Checkpoints
Transcriptional Activation
Lysine
Reactive Oxygen Species
Chemical activation
Association reactions
Neoplasms
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yamaguchi, H., Woods, N. T., Piluso, L. G., Lee, H. H., Chen, J., Bhalla, K. N., ... Wang, H. G. (2009). p53 acetylation is crucial for its transcription-independent proapoptotic functions. Journal of Biological Chemistry, 284(17), 11171-11183. https://doi.org/10.1074/jbc.M809268200

p53 acetylation is crucial for its transcription-independent proapoptotic functions. / Yamaguchi, Hirohito; Woods, Nicholas T; Piluso, Landon G.; Lee, Heng Huan; Chen, Jiandong; Bhalla, Kapil N.; Monteiro, Alvaro; Liu, Xuan; Hung, Mien Chie; Wang, Hong Gang.

In: Journal of Biological Chemistry, Vol. 284, No. 17, 24.04.2009, p. 11171-11183.

Research output: Contribution to journalArticle

Yamaguchi, H, Woods, NT, Piluso, LG, Lee, HH, Chen, J, Bhalla, KN, Monteiro, A, Liu, X, Hung, MC & Wang, HG 2009, 'p53 acetylation is crucial for its transcription-independent proapoptotic functions', Journal of Biological Chemistry, vol. 284, no. 17, pp. 11171-11183. https://doi.org/10.1074/jbc.M809268200
Yamaguchi, Hirohito ; Woods, Nicholas T ; Piluso, Landon G. ; Lee, Heng Huan ; Chen, Jiandong ; Bhalla, Kapil N. ; Monteiro, Alvaro ; Liu, Xuan ; Hung, Mien Chie ; Wang, Hong Gang. / p53 acetylation is crucial for its transcription-independent proapoptotic functions. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 17. pp. 11171-11183.
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