Hey1, a mediator of notch signaling, is an androgen receptor corepressor
Hey1, a mediator of notch signaling, is an androgen receptor corepressor
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DOI：
10.1128/mcb.25.4.1425-1436.2005
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发表时间：
2005-02-01
影响因子：
5.3
通讯作者：
Parker, MG
中科院分区：
文献类型：
--
作者：
Belandia, B;Powell, SM;Parker, MG
Hey1 是介导 Notch 信号转导的基本螺旋-环-螺旋-Orange 转录抑制因子家族的成员。在这里，我们表明，Hey1 抑制雄激素依赖性靶基因的转录，并且 Notch 的组成型活性形式的表达能够抑制内源雄激素受体 (AR) 的反式激活。我们的结果表明，Hey1 在 AR 中充当 AF1 的辅抑制子，为 Notch 和雄激素信号通路之间的串扰提供了机制。 Hey1 与良性前列腺增生患者上皮细胞中的 AR 共定位，在细胞质和细胞核中均存在。与此形成鲜明对比的是，我们证明，在大多数人类前列腺癌中，Hey1 被排除在细胞核之外，这提高了异常 Hey1 亚细胞分布可能在前列腺癌中观察到的异常激素反应中发挥作用的可能性。
Hey1 is a member of the basic helix-loop-helix-Orange family of transcriptional repressors that mediate Notch signaling. Here we show that transcription from androgen-dependent target genes is inhibited by Hey1 and that expression of a constitutively active form of Notch is capable of repressing transactivation by the endogenous androgen receptor (AR). Our results indicate that Hey1 functions as a corepressor for AF1 in the AR, providing a mechanism for cross talk between Notch and androgen-signaling pathways. Hey1 collocallizes with AR in the epithelia of patients with benign prostatic hyperplasia, where it is found in both the cytoplasm and the nucleus. In marked contrast, we demonstrate that Hey1 is excluded from the nucleus in most human prostate cancers, raising the possibility that an abnormal Hey1 subcellullar distribution may have a role in the aberrant hormonal responses observed in prostate cancer.