Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination

Cancer Cell. 2009 Apr 7;15(4):270-82. doi: 10.1016/j.ccr.2009.02.021.

Kexin Xu ¹, 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

Affiliations

Affiliation

1 Department of Pharmacology and Experimental Therapeutics and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

PMID: 19345326 DOI: 10.1016/j.ccr.2009.02.021

Abstract

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.

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