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

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

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)270-282
Number of pages13
JournalCancer Cell
Volume15
Issue number4
DOIs
StatePublished - Apr 7 2009
Externally publishedYes

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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