Binding of hormone accelerates the kinetics of glucocorticoid and progesterone receptor binding to DNA.
Binding of hormone accelerates the kinetics of glucocorticoid and progesterone receptor binding to DNA.
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激素的结合加速了糖皮质激素和黄体酮受体与 DNA 结合的动力学。
DOI：
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发表时间：
1989
影响因子：
11.1
通讯作者：
M. Beato
中科院分区：
文献类型：
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作者：
M. Schauer;G. Chalepakis;T. Willmann;M. Beato
类固醇激素受体通过与DNA调控序列相互作用来诱导基因。体内特定基因的荷尔蒙反应与荷尔蒙与受体的结合有关，并被认为反映了相应DNA调控序列的占用程度。然而，在体外，不含类固醇的糖皮质激素和孕激素受体与小鼠乳腺肿瘤病毒的调控序列特异结合，从而引发了关于激素在体内DNA结合中的作用的问题。通过使用单抗、凝胶滞留分析和过滤器结合技术，我们在这里展示了功能性类固醇与糖皮质激素或孕激素受体的结合影响体外蛋白质-DNA相互作用的动力学。在激素存在的情况下，受体与有或没有调控序列的DNA片段结合的开启速度加快了2-5倍，关闭速度加快了10-20倍。受体与抗激素结合在一起，与DNA结合，动力学介于非类固醇蛋白和激素结合蛋白之间。因此，配体结合加速了受体与DNA结合的动力学，这可能是体内观察到的激素受体行为的部分原因。
Steroid hormone receptors induce genes by virtue of their interaction with DNA regulatory sequences. The hormonal response of a particular gene in vivo correlates with binding of the hormone to the receptor and supposedly reflects the degree of occupancy of the corresponding DNA regulatory sequences. However, in vitro the steroid-free glucocorticoid and progesterone receptors bind specifically to the regulatory sequences of mouse mammary tumor virus, thus raising questions on the role of the hormone in DNA binding in vivo. By using monoclonal antibodies, gel retardation assays, and filter binding techniques we show here that binding of a functional steroid to either the glucocorticoid or the progesterone receptors influences the kinetics of the protein-DNA interaction in vitro. In the presence of hormone the on rate of receptor binding to DNA fragments with or without regulatory sequences is accelerated 2- to 5-fold, and the off rate is accelerated 10- to 20-fold. The receptors complexed to an antihormone bind to DNA with kinetics intermediate between those of the steroid-free and the hormone-bound protein. Thus, ligand binding accelerates the kinetics of receptor binding to DNA and this could partly account for the behavior of the hormone receptor observed in vivo.