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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coactivator AIB1 links estrogen receptor transcriptional activity and stability.
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Coactivator AIB1 links estrogen receptor transcriptional activity and stability.

机译：辅助激活剂AIB1连接雌激素受体的转录活性和稳定性。

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摘要

Agonist-mediated degradation of estrogen receptor alpha (ERalpha) has been associated with its transcriptional activity. However, the mechanism by which ERalpha is targeted for degradation and whether there is a direct functional link between ERalpha stability and ERalpha-mediated transactivation have not been elucidated. Here we provide evidence that the p160 coactivator, AIB1, uniquely mediates agonist-induced, but not antagonist-induced, ERalpha degradation. We show that AIB1 recruitment by ERalpha is not only necessary but also sufficient to promote degradation. Suppression of AIB1 levels leads to ERalpha stabilization in the presence of 17beta-estradiol and, despite increased ERalpha levels, reduced recruitment of ERalpha to endogenous target gene promoters. In addition, association of RNA polymerase II with ERalpha target promoters is lost when AIB1 is suppressed, leading to inhibition of target gene transcription. AIB1 thus plays a dual role in regulating ERalpha activity, one in recruiting transcription factors including other coactivators involved in gene activation and the other in regulating ERalpha protein degradation mediated by the ubiquitin-proteosome machinery.
机译：激动剂介导的雌激素受体α（ERalpha）的降解与其转录活性有关。但是，尚未阐明ERalpha靶向降解的机制以及ERalpha稳定性和ERalpha介导的反式激活之间是否存在直接的功能联系。在这里，我们提供的证据表明p160共激活因子AIB1独特地介导了激动剂诱导的但不是拮抗剂诱导的ERalpha降解。我们表明，ERalpha的AIB1募集不仅是必要的，而且足以促进降解。在存在17β-雌二醇的情况下，AIB1水平的抑制导致ERalpha稳定，尽管ERalpha水平升高，但减少了ERalpha向内源性靶基因启动子的募集。此外，当抑制AIB1时，RNA聚合酶II与ERalpha靶标启动子的结合会丢失，从而导致靶标基因转录的抑制。因此，AIB1在调节ERalpha活性中起着双重作用，一种在募集转录因子，包括参与基因激活的其他共激活因子，另一种在调节由遍在蛋白-蛋白体机制介导的ERalpha蛋白质降解中。

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