A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis
A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis
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YAP 和 NR4A1 之间的调节环平衡细胞增殖和凋亡
DOI：
10.1016/j.celrep.2020.108284
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发表时间：
2020-10-20
期刊：
影响因子：
8.8
通讯作者：
Zhang, Lei
中科院分区：
文献类型：
--
作者：
He, Lingli;Yuan, Liang;Zhang, Lei
Hippo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。这一途径如何触发细胞凋亡仍然在很大程度上未被探索。在此，我们将NR4A1鉴定为Hippo通路的靶点，其介导Hippo通路的促凋亡和抗肿瘤作用，其中雅普调节NR4A1的转录、磷酸化和线粒体定位，NR4A1反过来作为雅普的反馈抑制剂发挥作用以促进其降解，从而抑制雅普在肝再生和肿瘤发生期间的功能。我们的研究阐明了NR4A1和雅普之间的调节环，以协调肝再生和肿瘤发生过程中的Hippo信号转导活性，并强调NR4A1作为Hippo信号转导的标志物，以及肝细胞癌的治疗靶点。
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.