期刊
CANCER CELL
卷 15, 期 4, 页码 270-282出版社
CELL PRESS
DOI: 10.1016/j.ccr.2009.02.021
关键词
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资金
- NIH [CA106504, N01-CO-12400]
- US Department of Defense (DOD) [W81XWH-06-10199, W81XWH-08-1-0126]
- NCI [U01-CA86772]
- DOD Predoctoral Fellowship [W81XWH-06-1-0005, W81XWH08-1-0068]
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.
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