Coactivator/corepressor ratios modulate PR-mediated transcription by the selective receptor modulator RU486.
作者： Z. Liu , D. Auboeuf , J. Wong , J. D. Chen , S. Y. Tsai
关键词:
摘要: Selective receptor modulators, such as the antiprogestin RU486, are known to exhibit partial agonist activities in a cell-type-dependent manner. Employing an vitro chromatin transcription system that recapitulates progesterone (PR)-mediated vivo, we have investigated molecular basis by which RU486 regulates cell-type-specific We compared effects of on PR-dependent using T47D and HeLa cell nuclear extracts. exhibits differential ability activate within these two types. The effect correlates with different ratios endogenous coactivators/corepressors cells. Unlike agonist-bound PR interacts only coactivators steroid coactivator-1 (SRC-1), RU486-bound binds both coactivator SRC-1 corepressor silencing mediator for retinoid thyroid hormone (SMRT) vitro. Both SMRT capacity modulate RU486-dependent activity. Moreover, change relative levels contained our modulates agonist/antagonist PR. Our data indicate is modulated ratio corepressors substantiate important roles coregulators regulation mediated transactivation response selective modulators.
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