Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells
Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells
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DOI：
10.1038/sj.onc.1204489
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发表时间：
2001-06-28
期刊：
影响因子：
8
通讯作者：
Shuai, K
中科院分区：
文献类型：
--
作者：
Gross, M;Liu, B;Shuai, K
雄激素信号影响前列腺癌的发生和生长。雄激素受体（AR）的转录活性受阳性或阴性转录辅助因子的调控。我们报道了在人前列腺中表达的活化STAT （PIAS）蛋白抑制剂家族的PIAS1、PIAS3和PIASy对AR介导的前列腺癌细胞基因激活有不同的影响。虽然PIAS1和PIAS3增强AR的转录活性，但PIASy在前列腺癌细胞中作为AR的有效抑制剂，PIAS蛋白对AR的作用是竞争性的。PIASy与AR结合，但不影响AR的DNA结合活性。PIASy的nh2末端LXXLL特征基序虽然不是PIASy-AR相互作用所必需的，但对PIASy的转抑制活性至关重要。我们的研究结果确定PIASy是AR的转录辅抑制因子，并表明不同的PIAS蛋白对前列腺癌细胞中的AR信号传导有不同的影响。
Androgen signaling influences the development and growth of prostate carcinoma. The transcriptional activity of androgen receptor (AR) is regulated by positive or negative transcriptional cofactors, We report here that PIAS1, PIAS3, and PIASy of the protein inhibitor of activated STAT (PIAS) family, which are expressed in human prostate, display distinct effects on AR-mediated gene activation in prostate cancer cells. While PIAS1 and PIAS3 enhance the transcriptional activity of AR, PIASy acts as a potent inhibitor of AR in prostate cancer cells, The effects of PIAS proteins on AR are competitive. PIASy binds to AR but does not affect the DNA binding activity of AR. An NH2-terminal LXXLL signature motif of PIASy, although not required for PIASy-AR interaction, is essential for the transrepression activity of PIASy, Our results identify PIASy as a transcriptional corepressor of AR and suggest that different PIAS proteins have distinct effects on AR signaling in prostate cancer cells.