Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL
Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL
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UXT结合蛋白VHL对雄激素受体转录激活的调节
DOI：
10.1042/bj20121711
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发表时间：
2013-11-15
影响因子：
4.1
通讯作者：
Zhou, Rongjia
中科院分区：
文献类型：
--
作者：
Chen, Shuliang;Chen, Ke;Zhou, Rongjia
VHL（von Hippel-Lindau）肿瘤抑制因子的丢失和/或失活导致各种肿瘤。使用酵母双杂交系统，我们已经确定了AR（雄激素受体）辅激活剂UXT（遍在表达的转录本），作为一个VHL相互作用蛋白。GST pull-down和免疫共沉淀试验表明，UXT与VHL相互作用。此外，UXT将VHL募集到细胞核中。VHL与AR的DBD（DNA结合结构域）和铰链结构域结合并诱导AR泛素化。此外，VHL与AR的相互作用在DHT（二氢睾酮）处理后激活AR反式激活。VHL敲低抑制AR泛素化并降低AR的转录激活。我们的数据表明，VHL-UXT相互作用和VHL诱导的AR泛素化调节AR的转录激活。
Loss and/or inactivation of the VHL (von Hippel-Lindau) tumour suppressor causes various tumours. Using a yeast two-hybrid system, we have identified the AR (androgen receptor) coactivator UXT (ubiquitously expressed transcript), as a VHL-interacting protein. GST pull-down and co-immunoprecipitation assays show that UXT interacts with VHL. In addition, UXT recruits VHL to the nucleus. VHL associates with the DBD (DNA-binding domain) and hinge domains of the AR and induces AR ubiquitination. Moreover, VHL interaction with the AR activates AR transactivation upon DHT (dihydrotestosterone) treatment. VHL knockdown inhibits AR ubiquitination and decreases transcriptional activation of the AR. Our data suggest that the VHL-UXT interaction and VHL-induced ubiquitination of AR regulate transcriptional activation of the AR.