Regulation of Hsp90 client proteins by a Cullin5-RING E3 ubiquitin ligase

被引：99

作者：

Ehrlich, Elana S. ^{[1
]}

Wang, Tao ^{[1
]}

Luo, Kun ^{[1
]}

Xiao, Zuoxiang ^{[1
]}

Niewiadomska, Anna Maria ^{[1
]}

Martinez, Tara ^{[1
]}

Xu, Wanping ^{[2
]}

Neckers, Len ^{[2
]}

Yu, Xiao-Fang ^{[1
]}

机构：

[1] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[2] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 48期

关键词：

chaperone; erbb2; SOCS-BOX; ADENOVIRUS E4ORF6; BINDING DOMAIN; COMPLEX; DEGRADATION; CHAPERONE; VIF; ONCOPROTEINS; APOBEC3G; PATHWAY;

D O I：

10.1073/pnas.0810571106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We report a link between Cullin5 (Cul5) E3 ubiquitin ligase and the heat shock protein 90 (Hsp90) chaperone complex. Hsp90 participates in the folding of its client proteins into their functional conformation. Many Hsp90 clients have been reported to be aberrantly expressed in a number of cancers. We demonstrate Cul5 interaction with members of the Hsp90 chaperone complex as well as the Hsp90 client, ErbB2. We observed recruitment of Cul5 to the site of ErbB2 at the plasma membrane and subsequent induction of polyubiquitination and proteasomal degradation. We also demonstrate Cul5 involvement in regulation of another Hsp90 client, Hif-1 alpha. We observed Cul5 degradation of ErbB2 to occur independently of ElonginB-ElonginC function. The involvement of Cul5 in Hsp90 client regulation has implications in the effectiveness of Hsp90 targeted chemotherapy, which is currently undergoing clinical trials. The link between Cul5 and Hsp90 client regulation may represent an avenue for cancer drug development.

引用

页码：20330 / 20335

页数：6

共 35 条

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