[PDF][PDF] Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination

K Xu, H Shimelis, DE Linn, R Jiang, X Yang, F Sun… - Cancer cell, 2009 - cell.com
K Xu, H Shimelis, DE Linn, R Jiang, X Yang, F Sun, Z Guo, H Chen, W Li, H Chen, X Kong…
Cancer cell, 2009cell.com
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 …
Summary
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.
cell.com