Foxo1将胰岛素信号与C/EBPα联系起来，并在肝脏发育过程中调节糖异生。
Foxo1 links insulin signaling to C/EBPalpha and regulates gluconeogenesis during liver development.
作者信息
Sekine Keisuke, Chen Yen-Rong, Kojima Nobuhiko, Ogata Kazuhiro, Fukamizu Akiyoshi, Miyajima Atsushi
机构信息
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
出版信息
EMBO J. 2007 Aug 8;26(15):3607-15. doi: 10.1038/sj.emboj.7601784. Epub 2007 Jul 12.
Abstract
C/EBPalpha is a key transcription factor indispensable for the onset of gluconeogenesis in perinatal liver. However, C/EBPalpha was already expressed in fetal liver, suggesting that the expression of C/EBPalpha alone does not account for the dramatic increase of the expression of metabolic genes, and hence an additional factor(s) is expected to function cooperatively with C/EBPalpha in perinatal liver. We show here that expression of Foxo1 was sharply increased in the perinatal liver and augmented C/EBPalpha-dependent transcription. Foxo1 bound C/EBPalpha via its forkhead domain, and Foxo1 bound to the promoter of a gluconeogenic gene, phosphoenolpyruvate carboxykinase (PEPCK), in a C/EBPalpha-dependent manner in vivo. Insulin inhibited the expression of PEPCK in a culture of fetal liver cells, and also the C/EBPalpha-dependent transcription enhanced by Foxo1. These results indicate that Foxo1 regulates gluconeogenesis cooperatively with C/EBPalpha, and also links insulin signaling to C/EBPalpha during liver development.
摘要
C/EBPα是围产期肝脏中糖异生起始所必需的关键转录因子。然而，C/EBPα在胎儿肝脏中就已表达，这表明仅C/EBPα的表达并不能解释代谢基因表达的急剧增加，因此预计在围产期肝脏中有其他因子与C/EBPα协同发挥作用。我们在此表明，Foxo1在围产期肝脏中的表达急剧增加，并增强了C/EBPα依赖性转录。Foxo1通过其叉头结构域与C/EBPα结合，并且在体内Foxo1以C/EBPα依赖性方式与糖异生基因磷酸烯醇式丙酮酸羧激酶（PEPCK）的启动子结合。胰岛素在胎儿肝细胞培养物中抑制PEPCK的表达，以及Foxo1增强的C/EBPα依赖性转录。这些结果表明，Foxo1与C/EBPα协同调节糖异生，并且在肝脏发育过程中还将胰岛素信号传导与C/EBPα联系起来。
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