STRUCTURAL AND FUNCTIONAL DOMAINS OF THE ESTROGEN-RECEPTOR
STRUCTURAL AND FUNCTIONAL DOMAINS OF THE ESTROGEN-RECEPTOR
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DOI：
10.1101/sqb.1986.051.01.088
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发表时间：
1986-01-01
期刊：
影响因子：
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通讯作者：
CHAMBON, P
中科院分区：
文献类型：
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作者：
GREEN, S;KUMAR, V;CHAMBON, P
类固醇激素受体是靶细胞特异的转录调节介质，在发育过程中和在终末分化的细胞中都是如此(有关参考，请参阅Goldberger和Yamamoto 1984)。假设类固醇激素的结合诱导了受体结构的α-立体转变，从而使其能够控制特定基因转录的启动。人们还认为，激素受体复合体通过直接与激素反应基因的启动子元件结合而起到调节转录因子的作用(参考文献，见Yamamoto 1985；yon der Ahe et al.1986)。因此，类固醇激素受体至少应该包含两个功能结构域-一个用于结合类固醇，一个用于结合DNA-可能还有第三个功能结构域与转录机制相互作用，控制RNA合成的启动。因此，深入了解类固醇激素受体结构域的结构与功能关系，不仅是从分子水平上阐明激素作用机制的前提，而且有助于我们理解转录因子与启动子元件结合后如何控制转录的启动。与人类相对应的DNA(Walter等人1985年；格林等人。1986)和鸡肉(Krust等人1986年)雌激素受体(ER)，大鼠(Miesfeld等人)。1984、1986)和人类(Govindan等人)。1985年；Hollenberg等人。1985年)糖皮质激素受体(GRs)和鸡(Jeltsch等人)。1986)和人类(A.Krust等人，在准备中)孕激素受体(PR)已被不同程度地克隆和测序。人(HER)和鸡(CER)雌激素受体的序列比较显示了三个同源性区域，称为A、C和E，由同源性较低的B、D和F区域分隔(Krust等人)。1986年；另见无花果。LA和2)。C区在HER和CER之间100~保守，主要是亲水性的，以其高半胱氨酸和碱性氨基酸含量为特征；我们认为它对应于DNA结合区(Green等人。1986年；Krust等人。1986)。E区在HER和CER之间保守94%，主要是疏水的，我们提出它可能形成雌二醇配体的疏水口袋(Green等人)。1986年；Krust等人。1986)。与内质网C和E区显著同源的区域已在
Steroid hormone receptors are target cell-specific mediators of transcriptional regulation, both during development and in terminally differentiated cells (for references, see Goldberger and Yamamoto 1984). It is assumed that the binding of the steroid hormone induces an a| losteric transition of the structure of the receptor, such that it becomes capable of controlling initiation of transcription of specific genes. It is also believed that hormone-receptor complexes act as regulatory transcriptional factors by binding directly to promoter elements of hormone-responsive genes (for references, see Yamamoto 1985; yon der Ahe et al. 1986). As such, steroid hormone receptors should contain at least two functional domains-one for binding steroids and one for binding to DNA-and possibly a third one to interact with the transcription machinery to control initiation of RNA synthesis. Thus, a detailed knowledge of the structure-function relationship of steroid hormone receptor domains is not only a prerequisite for elucidating the mechanism of hormone action at the molecular level, but will also help us understand how transcription factors can control the initiation of transcription following their binding to promoter elements. cDNAs corresponding to the human (Walter et al. 1985; Green et al. 1986) and chicken (Krust et al. 1986) estrogen receptors (ERs), the rat (Miesfeld et al. 1984, 1986) and human (Govindan et al. 1985; Hollenberg et al. 1985) glucocorticoid receptors (GRs), and the chicken (Jeltsch et al. 1986) and human (A. Krust et al., in prep.) progesterone receptors (PRs) have been cloned and sequenced to various extents. A comparison between the sequence of the human (hER) and chick (cER) estrogen receptors has revealed three regions of homology, termed A, C, and E, separated by regions of lower homology, B, D, and F (Krust et al. 1986; see also Figs. la and 2). Region C, which is 100~ conserved between the hER and cER, is mainly hydrophilic and characterized by its high cysteine and basic amino acid content; we have suggested that it corresponds to the DNA-binding domain (Green et al. 1986; Krust et al. 1986). Region E, which is 94% conserved between the hER and cER, is mainly hydrophobic and we have proposed that it may form a hydrophobic pocket for the estradiol ligand (Green et al. 1986; Krust et al. 1986). Regions that are significantly homologous to regions C and E of the ERs have been found in the