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

详细信息    查看全文

• 作者：Kexin Xu ; Hermela Shimelis ; Douglas E. Linn ; Richeng Jiang ; Xi Yang ; Feng Sun ; Zhiyong Guo ; Hege Chen ; Wei Li ; Hegang Chen ; Xiangtian Kong ; Jonathan Melamed ; Shengyun Fang ; Zhen Xiao ; Timothy D. Veenstra ; Yun Qiu
• 刊名：Cancer Cell
• 出版年：2009
• 出版时间：7 April 2009
• 年：2009
• 卷：15
• 期：4
• 页码：270-282
• 全文大小：1752 K

文摘

Summary

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.