Central role of E3 ubiquitin ligase MG53 in insulin resistance and   metabolic disorders

doi:10.1038/nature11834

CORC > 北京大学 > 生命科学学院

	Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders
	Song, Ruisheng ; Peng, Wei ; Zhang, Yan ; Lv, Fengxiang ; Wu, Hong-Kun ; Guo, Jiaojiao ; Cao, Yongxing ; Pi, Yanbin ; Zhang, Xin ; Jin, Li ; Zhang, Mao ; Jiang, Peng ; Liu, Fenghua ; Meng, Shaoshuai ; Zhang, Xiuqin ; Jiang, Ping ; Cao, Chun-Mei ; Xiao, Rui-Ping
刊名	nature
	2013
关键词	SKELETAL-MUSCLE NEGATIVE REGULATOR DIABETES-MELLITUS RECEPTOR GLUCOSE OBESE DEGRADATION DYSFUNCTION RATS MICE
DOI	10.1038/nature11834
英文摘要	Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes(1). Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal(2,3), the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1); and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000315312900043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Multidisciplinary Sciences; SCI(E); PubMed; 43; ARTICLE; 7437; 375-379; 494
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/343025]
专题	生命科学学院
推荐引用方式 GB/T 7714	Song, Ruisheng,Peng, Wei,Zhang, Yan,et al. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders[J]. nature,2013.
APA	Song, Ruisheng.,Peng, Wei.,Zhang, Yan.,Lv, Fengxiang.,Wu, Hong-Kun.,...&Xiao, Rui-Ping.(2013).Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders.nature.
MLA	Song, Ruisheng,et al."Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders".nature (2013).