Luo J, Su F, Chen D, Shiloh A, Gu W
Institute of Cancer Genetics, and Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Nature. 2000 Nov 16;408(6810):377-81. doi: 10.1038/35042612.
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.
p53肿瘤抑制因子是一种转录因子，其活性受蛋白质稳定性和包括乙酰化在内的翻译后修饰调控。体内乙酰化p53得以维持的机制仍不清楚。在此我们表明，p53的去乙酰化由一个含组蛋白去乙酰化酶1（HDAC1）的复合物介导。我们还在去乙酰化酶复合物中纯化出一种p53靶蛋白（命名为PID；但与转移相关蛋白2（MTA2）相同），该蛋白已被鉴定为核小体重塑去乙酰化酶（NuRD）复合物的一个组分。PID在体外和体内均特异性地与p53相互作用，其表达显著降低乙酰化p53的稳态水平。PID表达强烈抑制p53依赖的转录激活，值得注意的是，它还调节p53介导的细胞生长停滞和凋亡。这些结果表明，由PID/MTA2相关的NuRD复合物进行的去乙酰化和功能相互作用可能代表了一条调节p53功能的重要途径。
