Joyeux A, Cavaillès V, Balaguer P, Nicolas J C
INSERM U439, Montpellier, France.
Mol Endocrinol. 1997 Feb;11(2):193-202. doi: 10.1210/mend.11.2.9884.
RIP140 has previously been cloned as a factor that interacts with the estrogen receptor (ER) in vitro. We demonstrate in this study that RIP140 is a co-factor for nuclear receptor in yeast. RIP140 enhances the ER transcriptional activity by increasing 1.5- to 4-fold the induction factor of the reporter gene response at saturating hormone concentrations, this effect being magnified at suboptimal doses of estradiol. Moreover, RIP140 decreases the ED50 of the dose-response curve. These effects are recovered with an N-terminal truncated ER, but impaired by point mutations that abolish AF2-AD activity. We did not observe any modulation of the partial agonist 4-hydroxytamoxifen activity in the presence of RIP140. Thus, RIP140 modulates transcriptional activity of ER through the AF2-AD domain and in a agonist-dependent fashion. RIP140 is also a strong coactivator for the retinoid pathway, as its expression enhances 10-fold the transactivation of a chimeric retinoic acid-alpha receptor at saturant hormone concentration and left shifted 5-fold the ED50 of the dose-response curve. We have investigated whether RIP140 could be involved in cross-talk between estrogenic and retinoid pathways.
RIP140先前已被克隆为一种在体外与雌激素受体（ER）相互作用的因子。我们在本研究中证明，RIP140是酵母中核受体的辅助因子。在饱和激素浓度下，RIP140通过将报告基因反应的诱导因子提高1.5至4倍来增强ER转录活性，在雌二醇次优剂量下这种效应会放大。此外，RIP140降低了剂量反应曲线的ED50。这些效应在N端截短的ER中得以恢复，但因消除AF2-AD活性的点突变而受损。在RIP140存在的情况下，我们未观察到部分激动剂4-羟基他莫昔芬活性的任何调节。因此，RIP140通过AF2-AD结构域并以激动剂依赖的方式调节ER的转录活性。RIP140也是类视黄醇途径的强共激活因子，因为在饱和激素浓度下其表达使嵌合视黄酸-α受体的反式激活增强10倍，并使剂量反应曲线的ED50向左移动5倍。我们研究了RIP140是否可能参与雌激素和类视黄醇途径之间的相互作用。
