Author/Authors :
Xu، نويسنده , , Kexin and Shimelis، نويسنده , , Hermela and Linn، نويسنده , , Douglas E. and Jiang، نويسنده , , Richeng and Yang، نويسنده , , Xi and Sun، نويسنده , , Feng and Guo، نويسنده , , Zhiyong and Chen، نويسنده , , Hege and Li، نويسنده , , Wei and Chen، نويسنده , , Hegang and Kong، نويسنده , , Xiangtian and Melamed، نويسنده , , Jonathan and Fang، نويسنده , , Shengyun and Xiao، نويسنده , , Zhen and Veenstra، نويسنده , , Timothy D. and Qiu، نويسنده , , Yun، نويسنده ,
Abstract :
Summary
drogen 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.
