Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination.
Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination.
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DOI：
10.1016/j.ccr.2009.02.021
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发表时间：
2009-04-07
期刊：
影响因子：
50.3
通讯作者：
Qiu Y
中科院分区：
文献类型：
--
作者：
Xu K;Shimelis H;Linn DE;Jiang R;Yang X;Sun F;Guo Z;Chen H;Li W;Chen H;Kong X;Melamed J;Fang S;Xiao Z;Veenstra TD;Qiu Y
雄激素受体（AR）在前列腺癌中起着关键作用。我们已经确定了泛素E3连接酶RNF6作为AR相关蛋白的蛋白质组学筛选。RNF6诱导AR泛素化并促进AR转录活性。RNF6的特异性敲除或RNF6诱导的AR上泛素化受体位点的突变选择性地改变了AR靶基因亚组的表达，并减少了AR及其共激活因子对这些基因调控区中存在的雄激素应答元件的募集。此外，RNF6在人难治性前列腺癌组织中过表达，并且在雄激素耗尽条件下是前列腺癌细胞生长所需的。我们的数据表明，RNF6诱导的泛素化可能通过调节辅因子的募集来调节AR的转录活性和特异性。
The androgen receptor (AR) plays a critical role in prostate cancer. We have identified an ubiquitin E3 ligase RNF6 as one of AR-associated proteins 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 human hormone-refractory 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 co-factor recruitment.