Pharmaceutical Sciences Faculty Publications
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
Recommended Citation
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.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/298
