Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-induced Ubiquitination

被引：228

作者：

Xu, Kexin ^{[1
,2
]}

Shimelis, Hermela ^{[1
,2
]}

Linn, Douglas E. ^{[1
,2
]}

Jiang, Richeng ^{[1
,2
]}

Yang, Xi ^{[1
,2
]}

Sun, Feng ^{[1
,2
]}

Guo, Zhiyong ^{[1
,2
]}

Chen, Hege ^{[1
,2
]}

Li, Wei ^{[1
,2
]}

Chen, Hegang ^{[3
]}

Kong, Xiangtian ^{[4
]}

Melamed, Jonathan ^{[4
]}

Fang, Shengyun ^{[5
]}

Xiao, Zhen ^{[6
]}

Veenstra, Timothy D. ^{[6
]}

Qiu, Yun ^{[1
,2
]}

机构：

[1] Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA

[3] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA

[4] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[5] Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Baltimore, MD 21201 USA

[6] SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, Frederick, MD 21702 USA

来源：

CANCER CELL | 2009年 / 15卷 / 04期

关键词：

RECURRENT PROSTATE-CANCER; CONJUGATING ENZYMES E2S; POLYUBIQUITIN CHAINS; TYROSINE PHOSPHORYLATION; DNA-REPAIR; PROTEIN; GENE; LIGASE; RING; DEGRADATION;

D O I：

10.1016/j.ccr.2009.02.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.

引用

页码：270 / 282

页数：13

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