Botrugno Oronza A, Fayard Elisabeth, Annicotte Jean-Sébastien, Haby Céline, Brennan Thomas, Wendling Olivia, Tanaka Toshiya, Kodama Tatsuhiko, Thomas Winston, Auwerx Johan, Schoonjans Kristina
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, 67404 Illkirch, France.
Mol Cell. 2004 Aug 27;15(4):499-509. doi: 10.1016/j.molcel.2004.07.009.
LRH-1 is an orphan nuclear receptor predominantly expressed in tissues of endodermal origin, where it controls development and cholesterol homeostasis. We show here that LRH-1 induces cell proliferation through the concomitant induction of cyclin D1 and E1, an effect that is potentiated by its interaction with beta-catenin. Whereas beta-catenin coactivates LRH-1 on the cyclin E1 promoter, LRH-1 acts as a potent tissue-restricted coactivator of beta-catenin on the cyclin D1 promoter. The implication of LRH-1 in cell proliferation highlights an unanticipated crosstalk between LRH-1 and the beta-catenin/Tcf4 signaling pathway, which is relevant for the renewal of intestinal crypt cells.
肝脏受体同源物-1（LRH-1）是一种主要在内胚层起源组织中表达的孤儿核受体，它在这些组织中控制发育和胆固醇稳态。我们在此表明，LRH-1通过同时诱导细胞周期蛋白D1和E1来诱导细胞增殖，这种效应因其与β-连环蛋白的相互作用而增强。虽然β-连环蛋白在细胞周期蛋白E1启动子上共同激活LRH-1，但LRH-1在细胞周期蛋白D1启动子上作为β-连环蛋白的一种有效的组织限制性共激活因子发挥作用。LRH-1在细胞增殖中的作用突出了LRH-1与β-连环蛋白/Tcf4信号通路之间意想不到的相互作用，这与肠隐窝细胞的更新有关。
