Deacetylation of p53 modulates its effect on cell growth and apoptosis

J. Luo, F. Su, D. Chen, Ariel L. Shiloh, W. Gu

Research output: Contribution to journalArticle

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Abstract

The p53 tumour suppressor is a transcriptional factor whose activity is modulated by protein stability and post-translational modifications including acetylation. The mechanism by which acetylated p53 is maintained in vivo remains unclear. Here we show that the deacetylation of p53 is mediated by an histone deacetylase-1 (HDAC1)-containing complex. We have also purified a p53 target protein in the deacetylase complexes (designated PID; but identical to metastasis-associated protein 2 (MTA2)), which has been identified as a component of the NuRD complex. PID specifically interacts with p53 both in vitro and in vivo, and its expression reduces significantly the steady-state levels of acetylated p53. PID expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-mediated cell growth arrest and apoptosis. These results show that deacetylation and functional interactions by the PID/MTA2associated NuRD complex may represent an important pathway to regulate p53 function.

Original languageEnglish (US)
Pages (from-to)377-381
Number of pages5
JournalNature
Volume408
Issue number6810
DOIs
StatePublished - Nov 16 2000
Externally publishedYes

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Mi-2 Nucleosome Remodeling and Deacetylase Complex
Histone Deacetylase 1
Apoptosis
Protein Stability
Post Translational Protein Processing
Acetylation
Growth
Transcriptional Activation
Proteins
Neoplasm Metastasis
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Deacetylation of p53 modulates its effect on cell growth and apoptosis. / Luo, J.; Su, F.; Chen, D.; Shiloh, Ariel L.; Gu, W.

In: Nature, Vol. 408, No. 6810, 16.11.2000, p. 377-381.

Research output: Contribution to journalArticle

Luo, J. ; Su, F. ; Chen, D. ; Shiloh, Ariel L. ; Gu, W. / Deacetylation of p53 modulates its effect on cell growth and apoptosis. In: Nature. 2000 ; Vol. 408, No. 6810. pp. 377-381.
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