A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen
A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen
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DOI：
10.1128/mcb.20.7.2411-2422.2000
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发表时间：
2000-04-01
影响因子：
5.3
通讯作者：
Kralli, A
中科院分区：
文献类型：
--
作者：
Knutti, D;Kaul, A;Kralli, A
类固醇受体以组织和配体特异性的方式介导对亲脂激素的反应。为了鉴定特异性或调节类固醇信号的非受体蛋白，我们筛选了一个类固醇敏感酵母菌的人类cDNA文库。其中一个鉴定的cdna，在筛选中作为配体效应调节剂6分离出来，与酵母或秀丽隐杆线虫蛋白没有同源性，但与最近描述的小鼠共激活因子PGC-1高度相似，因此被命名为hPGC-1。hPGC-1 DNA编码以组织特异性方式表达的核蛋白，并携带转录调节因子的新基序。哺乳动物细胞中hPGC-1的表达以受体特异性的方式增强了对几种类固醇的转录反应，hPGC-1介导的增强需要受体激素结合域，并且依赖于激动剂配体。hPGC-1的功能分析揭示了两个以激素依赖方式与类固醇受体相互作用的结构域，一个有效的转录激活功能和一个假定的二聚化结构域。我们的研究结果表明，hPGC-1作为核受体亚群的组织特异性共激活因子具有调节功能。
Steroid receptors mediate responses to lipophilic hormones in a tissue- and ligand-specific manner. To identify nonreceptor proteins that confer specificity or regulate steroid signaling, we screened a human cDNA library in a steroid-responsive yeast strain. One of the identified cDNAs, isolated in the screen as ligand effect modulator 6, showed no homology to yeast or Caenorhabditis elegans proteins but high similarity to the recently described mouse coactivator PGC-1 and was accordingly termed hPGC-1. The hPGC-1 DNA encodes a nuclear protein that is expressed in a tissue-specific manner and carries novel motifs for transcriptional regulators. The expression of hPGC-1 in mammalian cells enhanced potently the transcriptional response to several steroids in a receptor-specific manner, hPGC-1-mediated enhancement required the receptor hormone-binding domain and was dependent on agonist ligands. Functional analysis of hPGC-1 revealed two domains that interact with steroid receptors in a hormone-dependent manner, a potent transcriptional activation function, and a putative dimerization domain. Our findings suggest a regulatory function for hPGC-1 as a tissue-specific coactivator for a subset of nuclear receptors.