Deacetylation of p53 modulates its effect on cell growth and apoptosis.

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.
Authors	J Luo, F Su, D Chen, A Shiloh, W Gu
Journal	Nature (Nature) Vol. 408 Issue 6810 Pg. 377-81 (Nov 16 2000) ISSN: 0028-0836 [Print] England
PMID	11099047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	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
Topics	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)

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