Synergy between LRH-1 and β-catenin induces G1 cyclin-mediated cell proliferation
Synergy between LRH-1 and β-catenin induces G1 cyclin-mediated cell proliferation
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DOI：
10.1016/j.molcel.2004.07.009
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发表时间：
2004-08-27
期刊：
影响因子：
16
通讯作者：
Schoonjans, K
中科院分区：
文献类型：
--
作者：
Botrugno, OA;Fayard, E;Schoonjans, K
LRH-1是一种孤儿核受体，主要在内胚层组织中表达，在内胚层中控制发育和胆固醇稳态。我们在这里表明，LRH-1通过同时诱导细胞周期蛋白D1和Ell来诱导细胞增殖，这种作用通过与β -连环蛋白的相互作用而增强。β -连环蛋白协同激活细胞周期蛋白El启动子上的LRH-1，而LRH-1则是细胞周期蛋白D1启动子上β -连环蛋白的有效组织限制性协同激活因子。LRH-1在细胞增殖中的作用表明，LRH-1与β -catenin/Tcf4信号通路之间存在意想不到的串扰，这与肠隐窝细胞的更新有关。
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 Ell, an effect that is potentiated by its interaction with beta-catenin. Whereas beta-catenin coactivates LRH-1 on the cyclin El 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.