共查询到20条相似文献,搜索用时 203 毫秒
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Activation of estrogen receptor-alpha by the heavy metal cadmium 总被引:11,自引:0,他引:11
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The human estrogen receptor has transcriptional activator and repressor functions in the absence of ligand 总被引:7,自引:0,他引:7
Most studies on the cloned human estrogen receptor (hER) have been conducted with a mutant receptor in which Gly400 is changed to Val. Here we describe two novel regulatory functions of wild-type hER that are hormone independent: (i) a constitutive activator function and (ii) a repressor activity. Mutations in the hormone-binding domain, including the Val400 mutation, impair both of these functions. In addition, DNA binding is strongly reduced in the mutant receptors. The hormone-binding domain of the hER thus controls DNA binding (and thereby the repressor function) of the hER as well as its constitutive activator function. Moreover, we find that the antiestrogen tamoxifen restores the constitutive activator function, the DNA binding, and the repressor function of the Val400 mutant, but has no effect on the constitutive activator function or DNA binding of the wild-type hER. 相似文献
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J F Elliston S Y Tsai B W O'Malley M J Tsai 《The Journal of biological chemistry》1990,265(20):11517-11521
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V Laudet A Begue C Henry-Duthoit A Joubel P Martin D Stehelin S Saule 《Nucleic acids research》1991,19(5):1105-1112
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Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors. 总被引:20,自引:2,他引:18
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The glucocorticoid receptor accumulates in nuclei only in the presence of bound hormone, whereas the estrogen receptor has been reported to be constitutively nuclear. To investigate this distinction, we compared the nuclear localization domains of the two receptors and the capacity of their respective hormone-binding regions to regulate nuclear localization activity. As with the glucocorticoid receptor, we showed that the human estrogen receptor contained a nuclear localization signal between the DNA-binding and hormone-binding regions (amino acids 256-303); however, in contrast to the glucocorticoid receptor, the estrogen receptor lacked a second nuclear localization domain within the hormone-binding region. Moreover, the hormone-binding domain of the unliganded estrogen receptor failed to regulate nuclear localization signals, although it efficiently regulated other receptor functions. We conclude that the two receptors employ a common mechanism for signal transduction involving a novel "inactivation" function, but that they differ in their control of nuclear localization. Thus, despite the strong relatedness of the estrogen and glucocorticoid receptors in structure and activity, certain differences in their properties could have important functional implications. 相似文献
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Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor. 总被引:9,自引:10,他引:9
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J Casanova E Helmer S Selmi-Ruby J S Qi M Au-Fliegner V Desai-Yajnik N Koudinova F Yarm B M Raaka H H Samuels 《Molecular and cellular biology》1994,14(9):5756-5765