Deacetylation of p53 modulates its effect on cell growth and apoptosis.
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.
Luo
J
J
Institute of Cancer Genetics, and Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Su
F
F
Chen
D
D
Shiloh
A
A
Gu
W
W
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002352:Carrier Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D005982:Glutathione Transferase; C120917:MTA2 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex