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
  • 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.