Cato A C, Ponta H
Kernforschungszentrum Karlsruhe, Institut für Genetik und Toxikologie, Federal Republic of Germany.
Mol Cell Biol. 1989 Dec;9(12):5324-30. doi: 10.1128/mcb.9.12.5324-5330.1989.
Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.
如果雌激素和孕激素或雌激素和糖皮质激素受体的同源结合位点彼此靠近，它们在基因激活过程中会发生功能协同作用。这些相互作用被描述为类固醇受体作用的协同效应。尽管受体的蛋白质-蛋白质相互作用是最受青睐的模型之一，但实现协同效应的机制尚不清楚。在使用受体表达载体和含有雌激素及孕激素-糖皮质激素受体结合位点的报告基因进行的转染实验中，我们研究了各种受体的不同部分对协同作用的影响。鸡孕激素受体和人糖皮质激素受体的N端结构域缺失后，这些受体与雌激素受体的协同作用消失。雌激素受体的羧基末端氨基酸341至595缺失后产生了一个无法自行反式激活的突变受体。该突变受体不影响糖皮质激素受体的作用，但与孕激素受体协同发挥作用。因此，我们得出结论，雌激素和孕激素受体的协同作用机制与雌激素和糖皮质激素受体的协同作用机制不同。
