Negative Feedback at the Level of Nuclear Receptor Coregulation

摘要: Nuclear receptor-mediated gene expression is proposed to be regulated by the ordered recruitment of large protein complexes in which activity depends on mutual interactions and posttranslational modifications. In contrast, relatively little attention has been given mechanisms regulating coregulator proteins themselves. Previously we have shown that ligand-dependent corepressor, RIP140, a direct transcriptional target all-trans retinoic acid (RA). Here demonstrate RA induction RIP140 constitutes rate-limiting step regulation receptor signaling. Silencing dramatically enhances accelerates retinoid transactivation, endogenous other genes, RA-induced neuronal differentiation cell cycle arrest human embryonal carcinoma cells. The data suggest functional negative feedback loop limits activation receptors continued presence acutely coregulators may general regulatory mechanism hormonal