Cell growth and proliferation are tightly coupled to metabolism, and dissecting the signaling molecules which link these processes is an important step toward understanding development, regeneration, and cancer. The transcriptional regulator Yes-associated protein 1 (YAP) is a key regulator of liver size, development, and function. We now show that YAP can also suppress gluconeogenic gene expression. Yap deletion in primary hepatocytes potentiates the gluconeogenic gene response to glucagon and dexamethasone, whereas constitutively active YAP suppresses it. The effects of YAP are mediated by the transcriptional coactivator peroxisome proliferator–activated receptor-gamma coactivator 1. YAP inhibits its ability to bind to and activate transcription from the promoters of its gluconeogenic targets, and the effects of YAP are blunted upon its knockdown. In vivo, constitutively active YAP lowers plasma glucose levels and increases liver size.

中文翻译：

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YAP通过PGC1α抑制糖异生基因表达

细胞的生长和增殖与新陈代谢紧密相关，解剖连接这些过程的信号分子是理解发育，再生和癌症的重要一步。转录调节因子Yes相关蛋白1（YAP）是肝脏大小，发育和功能的关键调节因子。现在我们表明，YAP还可以抑制糖原异生基因的表达。p原发性肝细胞中的缺失增强了对胰高血糖素和地塞米松的糖异生基因反应，而组成型活性YAP抑制了它。YAP的作用是由转录共激活因子过氧化物酶体增殖物激活的受体-γ共激活因子1介导的。YAP抑制其与糖异生靶标的启动子结合并激活其转录的能力，并且在敲低YAP的作用就减弱了。在体内，组成型活性YAP降低血浆葡萄糖水平并增加肝脏大小。