YAP与NR4A1之间的调控环路平衡细胞增殖与凋亡。
A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis.
作者信息
He Lingli, Yuan Liang, Yu Wentao, Sun Yang, Jiang Dan, Wang Xiaodong, Feng Xue, Wang Zuoyun, Xu Jinjin, Yang Ruizeng, Zhang Wenxiang, Feng Hua, Chen Hang-Zi, Zeng Yi Arial, Hui Lijian, Wu Qiao, Zhang Yonglong, Zhang Lei
机构信息
State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
出版信息
Cell Rep. 2020 Oct 20;33(3):108284. doi: 10.1016/j.celrep.2020.108284.
The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation and apoptosis. How this pathway triggers cell apoptosis remains largely unexplored. Here, we identify NR4A1 as a target of the Hippo pathway that mediates the pro-apoptotic and anti-tumor effects of the Hippo pathway whereby YAP regulates the transcription, phosphorylation, and mitochondrial localization of NR4A1. NR4A1, in turn, functions as a feedback inhibitor of YAP to promote its degradation, thereby inhibiting the function of YAP during liver regeneration and tumorigenesis. Our studies elucidate a regulatory loop between NR4A1 and YAP to coordinate Hippo signaling activity during liver regeneration and tumorigenesis and highlight NR4A1 as a marker of Hippo signaling, as well as a therapeutic target for hepatocellular carcinoma.
河马信号通路通过协调细胞增殖和凋亡来维持器官大小和组织稳态。该通路如何触发细胞凋亡在很大程度上仍未得到探索。在此，我们确定NR4A1是河马通路的一个靶点，它介导河马通路的促凋亡和抗肿瘤作用，其中YAP调节NR4A1的转录、磷酸化和线粒体定位。反过来，NR4A1作为YAP的反馈抑制剂促进其降解，从而在肝脏再生和肿瘤发生过程中抑制YAP的功能。我们的研究阐明了NR4A1和YAP之间的调节环路，以在肝脏再生和肿瘤发生过程中协调河马信号活性，并突出了NR4A1作为河马信号的标志物以及肝细胞癌的治疗靶点。
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