Hdmx recruitment into the nucleus by Hdm2 is essential for its ability to regulate p53 stability and transactivation

被引:64
作者
Migliorini, D
Danovi, D
Colombo, E
Carbone, R
Pelicci, PG
Marine, JC
机构
[1] European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy
[2] FIRC, Inst Mol Oncol, I-20139 Milan, Italy
关键词
D O I
10.1074/jbc.M108795200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Hdmx gene product is related to the Hdm2 oncoprotein, both of which interact with and regulate p53 stability and function. Like Hdm2, Hdmx is able to inhibit p53 transactivation; however, at variance with Hdm2, which promotes ubiquitination, nuclear export, and degradation of p53, Hdmx increases p53 stability. We report here M that overexpressed Hdmx is cytoplasmic and Hdm2 recruits Hdmx into the nucleus and (ii) that nuclear Hdmx blocks Hdm2-mediated nuclear export of p53 and down-regulates p53-dependent transcription. Furthermore we showed that Hdmx inhibits Hdm2-mediated p53 ubiquitination. It appears, therefore, that a regulatory loop exists in which Hdm2 regulates the intracellular localization of Hdmx, and nuclear Hdmx regulates several functions of Hdm2 (ubiquitin ligase activity and p53 nuclear export).
引用
收藏
页码:7318 / 7323
页数:6
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