Regulation of Androgen Receptor by E3 Ubiquitin Ligases: for More or Less.
Regulation of Androgen Receptor by E3 Ubiquitin Ligases: for More or Less.
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DOI：
10.14800/rci.122
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
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作者：
Li B;Lu W;Chen Z
前列腺癌（Prostate cancer，PCa）的发生、发展以及化疗后的复发主要依赖于雄激素受体（androgen receptor，AR）信号通路的失调。雄激素剥夺治疗（ADT）有效地缓解了恶性肿瘤的症状，以阻止晚期PCa患者原发肿瘤的进一步生长或转移的进展。然而，许多患者在短期内复发，并且PCa细胞最终变得对ADT不敏感-称为去势抵抗性前列腺癌（CRPC）。AR信号转导机制的研究取得了巨大的进展，泛素化机制通过促进AR转录活性或降解AR蛋白水平直接或间接地参与了PCa的形成。最近的研究表明，SKP 2通过泛素介导的蛋白酶体降解来调节AR蛋白，突出了SKP 2在AR信号传导中的作用。鉴于AKT和SKP 2在癌症中的关键作用，各种E3连接酶的AR泛素化的差异机制对PCa控制具有有价值的意义和有益的影响。
Prostate cancer (PCa) primarily depends on the dysregulations of androgen receptor (AR) signaling pathway for the initiation and growth as well as recurrence after chemotherapy . Androgen deprivation therapy (ADT) effectively alleviates symptoms of the malignancy to arrest further growth of primary tumors or progression of metastasis in patients with advanced PCa. However, relapse occurs in many patients after a short period, and PCa cells eventually become insensitive to ADT - termed castration resistant prostate cancer (CRPC) . Tremendous advancements have been achieved to decipher the mechanisms on AR signaling, and the ubiquitination machinery contributes to PCa directly or indirectly by either promotion of AR transcriptional activity or degradation of AR protein levels. The recent report reveals that SKP2 regulates AR protein through ubiquitin-mediated proteasomal degradation, highlighting the role of SKP2 in AR signaling. Given the pivotal roles of AKT and SKP2 in cancers, the differential mechanisms of AR ubiquitination by various E3 ligases hold valuable significance and beneficial implications for PCa control.