Implications of ubiquitin ligases in castration-resistant prostate cancer.
Implications of ubiquitin ligases in castration-resistant prostate cancer.
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DOI：
10.1097/cco.0000000000000178
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发表时间：
2015-05
影响因子：
3.4
通讯作者：
Hussain A
中科院分区：
文献类型：
--
作者：
Qi J;Fan L;Hussain A
泛素化介导的雄激素受体(AR)调节的研究取得了重大进展。这篇综述将突出E3泛素连接酶控制AR活性的机制的最新进展，并与去势耐受前列腺癌(CRPC)有关。一些泛素连接酶已被发现与AR相互作用并使其泛化，从而对AR转录程序进行正向或负向调节。不同的泛素连接酶可以使用不同的机制来调节AR靶基因的表达，包括AR染色质复合体的局部周转，AR共激活因子的募集，以及AR的整体稳定性。泛素连接酶在前列腺癌中的表达或活性可以改变，从而通过调节AR转录活性促进雄激素不敏感的前列腺癌细胞的生长。了解泛素连接酶对AR转录活性的调控将有助于阐明AR重新激活的机制，这被认为是推动CPPC发展的机制。泛素连接酶可能成为开发治疗晚期前列腺癌的治疗方法的潜在靶点。
Significant advances have been made in the study of ubiquitination-mediated regulation of androgen receptor (AR). This review will highlight the latest developments in the mechanisms by which E3 ubiquitin ligases control AR activity, with implications in castration-resistant prostate cancer (CRPC). Several ubiquitin ligases have been identified to interact with and ubiquitinate AR, and consequently regulate positively or negatively e the AR transcriptional program.. Different ubiquitin ligases can use distinct mechanisms to modulate the expression of AR target genes, including local turnover of AR chromatin complex, recruitment of AR co-activators, and global AR stability. The expression or activity of ubiquitin ligases can be altered in prostate cancer and thus contribute to the growth of androgen-insensitive prostate cancer cells by modulating the AR transcriptional activity. Understanding the regulation of AR transcriptional activity by ubiquitin ligases will contribute to the elucidation of mechanisms underlying AR re-activation that is believed to drive the development of CPPC. Ubiquitin ligases could potentially serve as promising targets for developing therapeutics in the treatment of advanced prostate cancers.