Pharmaceutical Sciences Faculty Publications

Title

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

Document Type

Article

Publication Date

4-7-2009

Journal Title

Cancer Cell

ISSN

1878-3686

Volume

15

Issue

4

First Page

270

Last Page

282

DOI

10.1016/j.ccr.2009.02.021

PubMed ID

19345326

PubMed Central® ID

PMC2848969

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.

Keywords

Amino acid sequence, androgens, cells, cultured, chromatin immunoprecipitation, DNA-binding proteins, kidney, neoplasms, RNA, messenger, receptors, transcription, genetic, ubiquitination

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