Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26

被引：74

作者：

Zhang, Ying ^{[1
]}

Wang, Jian ^{[1
]}

Yuan, Yanzhi ^{[1
]}

Zhang, Wanqiao ^{[1
]}

Guan, Wei ^{[1
]}

Wu, Zhihao ^{[1
]}

Jin, Chaozhi ^{[1
]}

Chen, Hui ^{[1
]}

Zhang, Lingqiang ^{[1
]}

Yang, Xiaoming ^{[1
]}

He, Fuchu ^{[1
,2
]}

机构：

[1] Beijing Proteome Res Ctr, Beijing Inst Radiat Med, State Key Lab Prote, Beijing 102206, Peoples R China

[2] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

来源：

NUCLEIC ACIDS RESEARCH | 2010年 / 38卷 / 19期

关键词：

FINGER DOMAIN; MDM2; L11; TRANSLATION; INHIBITION; ACTIVATION; L5; UBIQUITINATION; ACETYLATION; PATHWAY;

D O I：

10.1093/nar/gkq536

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：

HDM2 is a p53-specific E3 ubiquitin ligase. Its overexpression leads to excessive inactivation of tumor protein p53, diminishing its tumor suppressor function. HDM2 also affects the cell cycle, apoptosis and tumorigenesis through interacting with other molecules, including several ribosomal proteins. To identify novel HDM2 regulators, we performed a yeast two-hybrid screening using HDM2 as bait. Among the candidates, ribosomal protein L26 (RPL26) was characterized as a novel HDM2-interactor. The interaction between HDM2 and RPL26 was further validated by in vivo and in vitro assays. RPL26 modulates the HDM2-p53 interaction by forming a ternary complex among RPL26, HDM2 and p53, which stabilize p53 through inhibiting the ubiquitin ligase activity of HDM2. The ribosomal stress caused by a low dose of Act D enhances RPL26-HDM2 interaction and activates p53. Overexpression of RPL26 results in activating of p53, inhibits cell proliferation and induces a p53-dependent cell cycle arrest. These results provide a novel regulatory mechanism of RPL26 to activate p53 by inhibiting HDM2.

引用

页码：6544 / 6554

页数：11

共 25 条

[1] Stress signals utilize multiple pathways to stabilize p53 [J].