Deacetylation of p53 Modulates Its Effect on Cell Growth and Apoptosis

Nature. 2000 Nov 16;408(6810):377-81. doi: 10.1038/35042612.

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/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Carrier Proteins / metabolism
  • Cell Division*
  • Cell Line
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Histone Deacetylase 1
  • Histone Deacetylases / metabolism*
  • Humans
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Proteins / metabolism
  • Recombinant Fusion Proteins
  • Repressor Proteins*
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Carrier Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • Glutathione Transferase
  • MTA2 protein, human
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Sin3 Histone Deacetylase and Corepressor Complex

Associated data

  • GENBANK/AF295807