Katz Liora S, Baumel-Alterzon Sharon, Scott Donald K, Herman Mark A
Icahn School of Medicine at Mount Sinai, Obesity, Diabetes and Metabolism Institute, New York, New York, USA.
Icahn School of Medicine at Mount Sinai, Obesity, Diabetes and Metabolism Institute, New York, New York, USA.
J Biol Chem. 2021 Jan-Jun;296:100623. doi: 10.1016/j.jbc.2021.100623. Epub 2021 Apr 2.
Excessive sugar consumption is a contributor to the worldwide epidemic of cardiometabolic disease. Understanding mechanisms by which sugar is sensed and regulates metabolic processes may provide new opportunities to prevent and treat these epidemics. Carbohydrate Responsive-Element Binding Protein (ChREBP) is a sugar-sensing transcription factor that mediates genomic responses to changes in carbohydrate abundance in key metabolic tissues. Carbohydrate metabolites activate the canonical form of ChREBP, ChREBP-alpha, which stimulates production of a potent, constitutively active ChREBP isoform called ChREBP-beta. Carbohydrate metabolites and other metabolic signals may also regulate ChREBP activity via posttranslational modifications including phosphorylation, acetylation, and O-GlcNAcylation that can affect ChREBP's cellular localization, stability, binding to cofactors, and transcriptional activity. In this review, we discuss mechanisms regulating ChREBP activity and highlight phenotypes and controversies in ChREBP gain- and loss-of-function genetic rodent models focused on the liver and pancreatic islets.
过量摄入糖分是导致全球心血管代谢疾病流行的一个因素。了解糖分被感知以及调节代谢过程的机制，可能为预防和治疗这些流行病提供新的机会。碳水化合物反应元件结合蛋白（ChREBP）是一种糖感应转录因子，它介导关键代谢组织中对碳水化合物丰度变化的基因组反应。碳水化合物代谢产物激活ChREBP的经典形式ChREBP-α，后者刺激产生一种强效的、组成型活性的ChREBP异构体，称为ChREBP-β。碳水化合物代谢产物和其他代谢信号也可能通过翻译后修饰（包括磷酸化、乙酰化和O-连接的N-乙酰葡糖胺化）来调节ChREBP的活性，这些修饰会影响ChREBP的细胞定位、稳定性、与辅因子的结合以及转录活性。在这篇综述中，我们讨论调节ChREBP活性的机制，并重点介绍聚焦于肝脏和胰岛的ChREBP功能获得和功能丧失基因啮齿动物模型中的表型及争议。
