FHL2，一种新型的雄激素受体组织特异性共激活因子。
FHL2, a novel tissue-specific coactivator of the androgen receptor.
作者信息
Müller J M, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schüle R
机构信息
Universitäts-Frauenklinik, Abteilung Frauenheilkunde und Geburtshilfe I, Klinikum der Universität Freiburg, Breisacherstrasse 117, 79106 Freiburg, Germany.
出版信息
EMBO J. 2000 Feb 1;19(3):359-69. doi: 10.1093/emboj/19.3.359.
The control of target gene expression by nuclear receptors requires the recruitment of multiple cofactors. However, the exact mechanisms by which nuclear receptor-cofactor interactions result in tissue-specific gene regulation are unclear. Here we characterize a novel tissue-specific coactivator for the androgen receptor (AR), which is identical to a previously reported protein FHL2/DRAL with unknown function. In the adult, FHL2 is expressed in the myocardium of the heart and in the epithelial cells of the prostate, where it colocalizes with the AR in the nucleus. FHL2 contains a strong, autonomous transactivation function and binds specifically to the AR in vitro and in vivo. In an agonist- and AF-2-dependent manner FHL2 selectively increases the transcriptional activity of the AR, but not that of any other nuclear receptor. In addition, the transcription of the prostate-specific AR target gene probasin is coactivated by FHL2. Taken together, our data demonstrate that FHL2 is the first LIM-only coactivator of the AR with a unique tissue-specific expression pattern.
核受体对靶基因表达的调控需要募集多种辅因子。然而，核受体与辅因子相互作用导致组织特异性基因调控的确切机制尚不清楚。在此，我们鉴定了一种新的雄激素受体（AR）组织特异性共激活因子，它与先前报道的功能未知的蛋白FHL2/DRAL相同。在成体中，FHL2在心脏的心肌和前列腺的上皮细胞中表达，在细胞核中它与AR共定位。FHL2具有强大的自主反式激活功能，在体外和体内均能特异性结合AR。FHL2以激动剂和AF-2依赖的方式选择性地增强AR的转录活性，但不增强任何其他核受体的转录活性。此外，前列腺特异性AR靶基因前列腺素的转录由FHL2共同激活。综上所述，我们的数据表明FHL2是首个具有独特组织特异性表达模式的AR仅含LIM结构域的共激活因子。
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