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• W1569540889 endingPage "19520" @default.
• W1569540889 startingPage "19513" @default.
• W1569540889 abstract "Antihormones are potent antagonists of hormone action in vivo, but the mechanism underlying this antagonism is not understood. Several steroid hormones transform (activate) their receptors from a cytosolic, non-DNA binding 8 S sedimentation form to a nuclear, DNA binding 4 S form. Transformation is accompanied by the loss of associated heat shock proteins. We have previously demonstrated that an additional hormone-dependent step, separate from heat shock protein removal, is required for activation of the human progesterone receptor. We have devised an assay in which the human progesterone receptor translated in vitro binds to its specific response element in a hormone-dependent manner. As assessed by limited proteolytic digestion, hormone treatment of the nascent receptor induces a dramatic conformational change within the protein. The conformational change occurs in the absence of DNA and renders the entire ligand binding domain resistant to digestion by proteases. A number of antiprogestins, including RU486, induce an equally dramatic, but distinct, structural alteration of the ligand binding domain. The distinction centers upon the final 30 to 40 amino acids at the carboxyl terminus. The conformational change can be induced by ligand prior to dissociation of the 8 S complex and is not induced by heat shock protein removal in the absence of hormone. Remarkably, virtually identical hormone-induced conformational changes were detected following proteolytic analysis of in vitro translated retinoic acid receptors. Our data indicate that the sole necessary event in the activation of steroid receptors is conformational modification by the ligand. Furthermore, we conclude that transcriptional inactivation of steroid receptors by antihormones involves the induction of an inappropriate structural conformation at the extreme carboxyl terminus of the ligand binding domain." @default.
• W1569540889 created "2016-06-24" @default.
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• W1569540889 date "1992-09-01" @default.
• W1569540889 modified "2023-10-01" @default.
• W1569540889 title "Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation." @default.
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• W1569540889 doi "https://doi.org/10.1016/s0021-9258(18)41805-4" @default.
• W1569540889 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1326555" @default.
• W1569540889 hasPublicationYear "1992" @default.
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