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
Available at: http://works.bepress.com/timothy-veenstra/132/