Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination
PubMed Central® ID
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.
Amino acid sequence, androgens, cells, cultured, chromatin immunoprecipitation, DNA-binding proteins, kidney, neoplasms, RNA, messenger, receptors, transcription, genetic, ubiquitination
Xu, Kexin; Shimelis, Hermela; Linn, Douglas E.; Jiang, Richeng; Yang, Xi; Sun, Feng; Guo, Zhiyong; Chen, Hege; Li, Wei; Chen, Hegang; Kong, Xiangtian; Melamed, Jonathan; Fang, Shengyun; Xiao, Zhen; Veenstra, Timothy D.; and Qiu, Yun, "Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination" (2009). Pharmaceutical Sciences Faculty Publications. 298.