Tora L, Gronemeyer H, Turcotte B, Gaub M P, Chambon P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de l'INSERM, Faculté de Médecine, Strasbourg, France.
Nature. 1988 May 12;333(6169):185-8. doi: 10.1038/333185a0.
Steroid hormone receptors belong to a family of nuclear receptors that trigger transcriptional activation of target genes by specific binding to DNA recognition sequences, usually located in the 5'-flanking region of the target gene. Nuclear receptors appear to be segmented proteins and extensive structure-function analyses have attempted to elucidate the functional significance of individual segments. Two of these regions have been defined as the domains responsible for recognition of responsive elements of target genes (region C) and hormone binding (region E) (refs 2-7). But the functional significance of the N-terminal region (A/B), which diverges extensively even for a given receptor between different species, has remained obscure. We have previously cloned, expressed and analysed the chicken progesterone receptor (cPR) (ref. 8). This receptor and its human homologue from T47D breast cancer cells are unique among the steroid hormone receptors in that two forms, A and B, are present in equal amounts in cytosolic extracts, the latter having the higher molecular weight. For the chicken progesterone receptor, we have presented evidence suggesting that the cPR form A corresponds to an N-terminally truncated form of B (ref. 8). Here we report on the functional difference between the forms A and B in the transcriptional activation of two target genes.
类固醇激素受体属于核受体家族，通过与通常位于靶基因5'侧翼区域的DNA识别序列特异性结合来触发靶基因的转录激活。核受体似乎是分段蛋白，广泛的结构-功能分析试图阐明各个片段的功能意义。其中两个区域已被定义为负责识别靶基因反应元件的结构域（C区域）和激素结合结构域（E区域）（参考文献2-7）。但是N端区域（A/B）的功能意义仍然不清楚，即使对于给定受体，该区域在不同物种之间也存在很大差异。我们之前已经克隆、表达并分析了鸡孕酮受体（cPR）（参考文献8）。该受体及其来自T47D乳腺癌细胞的人类同源物在类固醇激素受体中是独特的，因为在胞质提取物中两种形式A和B等量存在，后者分子量更高。对于鸡孕酮受体，我们已经提供了证据表明cPR的A形式对应于B的N端截短形式（参考文献8）。在此我们报告A和B两种形式在两个靶基因转录激活中的功能差异。
