Deacetylation of p53 modulates its effect on cell growth and apoptosis

The p53 tumour suppressor is a transcriptional factor whose activity is mod ulated by protein stability and post-translational modifications including acetylation(1-4). The mechanism by which acetylated p53 is maintained in vi vo remains unclear. Here we show that the deacetylation of p53 is mediated by an histone deacetylase-1 (HDAC1)-containing complex. We have also purifi ed a p53 target protein in the deacetylase complexes (designated PID; but i dentical to metastasis-associated protein 2 (MTA2)), which has been identif ied as a component of the NuRD complex(5-7). PID specifically interacts wit h p53 both in vitro and in vivo, and its expression reduces significantly t he steady-state levels of acetylated p53. PID expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-m ediated cell growth arrest and apoptosis. These results show that deacetyla tion and functional interactions by the PID/MTA2-associated NuRD complex ma y represent an important pathway to regulate p53 function.