Pearce D, Yamamoto K R
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Science. 1993 Feb 19;259(5098):1161-5. doi: 10.1126/science.8382376.
Mineralocorticoid and glucocorticoid hormones elicit distinct physiologic responses, yet the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) bind to and activate transcription similarly from a consensus simple hormone response element (HRE). The activities of GR and MR at plfG, a 25-base pair composite response element to which both the steroid receptors and transcription factor AP1 can bind, are analyzed here. Under conditions in which GR represses AP1-stimulated transcription from plfG, MR was inactive. With the use of MR-GR chimeras, a segment of the NH2-terminal region of GR (amino acids 105 to 440) was shown to be required for this repression. Thus, the distinct physiologic effects mediated by MR and GR may be determined by differential interactions of nonreceptor factors with specific receptor domains at composite response elements.
盐皮质激素和糖皮质激素引发不同的生理反应,然而盐皮质激素受体(MR)和糖皮质激素受体(GR)从一个共有简单激素反应元件(HRE)上类似地结合并激活转录。本文分析了GR和MR在plfG上的活性,plfG是一个25个碱基对的复合反应元件,类固醇受体和转录因子AP1均可与之结合。在GR抑制AP1刺激的plfG转录的条件下,MR无活性。通过使用MR-GR嵌合体,发现GR的NH2末端区域的一段(氨基酸105至440)是这种抑制所必需的。因此,MR和GR介导的不同生理效应可能由非受体因子与复合反应元件上特定受体结构域的差异相互作用所决定。