Regulation of expression of the steroidogenic acute regulatory protein (StAR) gene: A central role for steroidogenic factor 1
Regulation of expression of the steroidogenic acute regulatory protein (StAR) gene: A central role for steroidogenic factor 1
复制标题
DOI：
10.1016/s0039-128x(96)00152-3
复制
发表时间：
1997-01-01
期刊：
影响因子：
2.7
通讯作者：
Strauss, JF
中科院分区：
文献类型：
--
作者：
Sugawara, T;Kiriakidou, M;Strauss, JF
甾体源性急性调节蛋白（StAR）在类固醇激素合成的限速步骤胆固醇侧链裂解中起关键作用。在性腺中，StAR基因的表达是由促性腺激素通过cAMP第二信息转录控制的。我们已经开始分析导致StAR基因转录激活的因素。人类SrAR基因启动子至少有两个顺式元件控制基础和camp调控的基因表达。其中一个元件（远端元件）是孤儿核受体转录因子类固醇生成因子1 （SF-1）的一致结合序列；另一个（近端元素）是一个相关的母题。人StAR启动子在BeWo绒毛膜癌细胞中不活跃，但在小鼠Y1肾上腺皮质肿瘤细胞中具有功能性和camp响应性。共转染表达SF-1的质粒可以使StAR启动子在BeWo细胞中发挥作用。其他孤儿核转录因子在BeWo细胞宿主中不支持StAR启动子功能。远端和近端顺式元件的缺失或突变分别大大降低了SF-1支持的StAR启动子活性，远端位点与SF-1具有高亲和力，而近端位点与SF-1具有低亲和力。这些发现表明，人类StAR基因的表达需要SF-1。(C) 1997年由爱思唯尔科学公司
Steroidogenic acute regulatory protein (StAR) plays a critical role in regulating the rate-limiting step in steroid hormone synthesis, cholesterol side-chain cleavage. StAR gene expression is transcriptionally controlled in the gonads by gonadotropic hormones via a cAMP second message. We have begun to analyze factors responsible for the transcriptional activation of the StAR gene. The human SrAR gene promoter has at least two cis elements that govern basal and cAMP-regulated gene expression. One of these elements (the distal element) is a consensus binding sequence for the orphan nuclear receptor transcription factor, steroidogenic factor 1 (SF-1); the other (the proximal element) is a related motif. The human StAR promoter is not active in BeWo choriocarcinoma cells, but is functional and cAMP-responsive in murine Y1 adrenal cortical tumor cells. Cotransfection of a plasmid expressing SF-1 allows a StAR promoter construct to function in BeWo cells. Other orphan nuclear transcription factors do not support StAR promoter function in BeWo cell hosts. Deletion or mutation of the distal and proximal cis elements individually substantially reduces SF-1-supported StAR promoter activity The distal site binds SF-1 with high affinity whereas the proximal site binds SF-1 with lower affinities. These findings demonstrate a requirement for SF-1 for human StAR gene expression. (C) 1997 by Elsevier Science Inc.