The Von Hippel-Lindau Protein Suppresses Androgen Receptor Activity
The Von Hippel-Lindau Protein Suppresses Androgen Receptor Activity
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Von Hippel-Lindau 蛋白抑制雄激素受体活性
DOI：
10.1210/me.2013-1258
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发表时间：
2014-02-01
影响因子：
--
通讯作者：
Xiao, Wuhan
中科院分区：
文献类型：
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作者：
Wang, Jing;Zhang, Wei;Xiao, Wuhan
雄激素受体（AR）在前列腺稳态和前列腺癌的发展中起着关键作用。了解AR调控的机制有助于开发新的前列腺癌治疗方法。在这里，我们发现Von Hippel-Lindau基因产物pVHL与AR物理相互作用并抑制AR转录活性，但不诱导AR周转。此外，pVHL还能抑制雄激素诱导的细胞增殖，提示pVHL在雄激素诱导的信号通路中具有生理作用。此外，我们提供的证据表明pVHL实际上增强了AR去泛素化，而不是诱导AR泛素化，揭示了pVHL在泛素蛋白酶体途径中的非规范作用。我们的数据揭示了pVHL在调节AR转录活性中的新功能，这可能扩大pVHL在肿瘤抑制中的范围，并为前列腺癌的发生和进展提供机制见解。
The androgen receptor (AR) plays a pivotal role in prostate homeostasis and prostate cancer development. To understand the mechanism underlying the regulation of the AR holds a promise for developing novel therapeutic approaches for prostate cancer. Here, we show that the Von Hippel-Lindau gene product, pVHL, physically interacts with AR and inhibits AR transcription activity but does not induce AR turnover. Moreover, pVHL also suppresses androgen-induced cell proliferation, implicating a physiological role of pVHL in androgen-induced signaling pathway. In addition, we provide evidence to show that pVHL actually enhanced AR de-ubiquitination instead of inducing AR ubiquitination, uncovering a noncanonical role of pVHL in the ubiquitin proteasome pathway. Our data reveal a novel function of pVHL in the regulation of AR transcription activity, which may expand the scope of pVHL in tumor suppression and provide mechanistic insight into prostate cancer initiation and progression.