Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination.
Article Details
- CitationCopy to clipboard
Xu K, Shimelis H, Linn DE, Jiang R, Yang X, Sun F, Guo Z, Chen H, Li W, Chen H, Kong X, Melamed J, Fang S, Xiao Z, Veenstra TD, Qiu Y
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.
- PubMed ID
- 19345326 [ View in PubMed]
- 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.