MDM2和ARF对p53泛素化及核输出的调控

Control of p53 ubiquitination and nuclear export by MDM2 and ARF.

作者信息

Zhang Y, Xiong Y

机构信息

Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Cell Growth Differ. 2001 Apr;12(4):175-86.

PMID:11331246

Abstract

p53 and ARF-INK4a are the two most frequently altered loci in human tumors. The activity of p53 protein is inhibited during normal cell growth by the proto-oncoprotein MDM2 through either repression of p53-mediated transcription in the nucleus or proteasomal degradation of p53 protein in the cytoplasm. Responding to oncogenic signal-activated cell hyperproliferation, ARF-mediated antagonism of MDM2 inhibition results in p53 becoming active and its protein levels rising. The biochemical mechanisms of ubiquitination and nuclear export that underlie the functions of ARF and MDM2 in p53 control continue to emerge.

摘要

p53和ARF-INK4a是人类肿瘤中两个最常发生改变的基因座。在正常细胞生长过程中，原癌蛋白MDM2通过抑制细胞核中p53介导的转录或细胞质中p53蛋白的蛋白酶体降解来抑制p53蛋白的活性。作为对致癌信号激活的细胞过度增殖的反应，ARF介导的对MDM2抑制的拮抗作用导致p53变得活跃，其蛋白水平升高。ARF和MDM2在p53调控中发挥作用的泛素化和核输出的生化机制仍在不断揭示中。