Hollenberg S M, Giguere V, Segui P, Evans R M
Cell. 1987 Apr 10;49(1):39-46. doi: 10.1016/0092-8674(87)90753-7.
Using a combination of a transient expression assay and in vitro mutagenesis, we showed previously that the human glucocorticoid receptor (hGR) is composed of a series of discrete functional domains. Here we report the effects of selective deletion of each of these domains on hGR ability to activate transcription of the MTV-CAT fusion gene. Deletion of the immunogenic domain or the entire amino-terminal half of the protein reduces but does not abolish the ability of the hGR to induce transcriptional activation. Somewhat surprisingly, deletion of the steroid-binding domain engenders a constitutively active receptor, revealing that this domain normally represses receptor function. However, the central, cysteine-rich region contains all the information required for both DNA binding and trans-activation. Taken together, these data delineate a core domain in the hGR spanning 88 amino acids that determines both DNA-binding and transcriptional activation functions. This physical linkage distinguishes the glucocorticoid receptor from other described eukaryotic regulatory proteins, where these two functions have been shown to be separable.
通过瞬时表达分析和体外诱变相结合的方法，我们先前已表明人糖皮质激素受体（hGR）由一系列离散的功能域组成。在此我们报告选择性缺失这些结构域中的每一个对hGR激活MTV-CAT融合基因转录能力的影响。免疫原性结构域或蛋白质整个氨基末端一半的缺失会降低但不会消除hGR诱导转录激活的能力。有点令人惊讶的是，类固醇结合结构域的缺失产生了一种组成型活性受体，这表明该结构域通常会抑制受体功能。然而，中央富含半胱氨酸的区域包含DNA结合和反式激活所需的所有信息。综上所述，这些数据描绘了hGR中一个跨越88个氨基酸的核心结构域，该结构域决定了DNA结合和转录激活功能。这种物理联系将糖皮质激素受体与其他已描述的真核调节蛋白区分开来，在其他真核调节蛋白中，这两种功能已被证明是可分离的。
