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MG53 is a double-edged sword for human diseases

ZHANG Yan, WU Hong-Kun, LV Feng-Xiang, XIAO Rui-Ping

State Key Laboratory of Membrane Biology, Institute of Molecular Medicine； Peking-Tsinghua Center for Life Sciences and Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China

Abstract

Mitsugumin 53 (MG53), also named Trim72, is a multi-functional TRIM-family protein, which is abundantly expressed in cardiac and skeletal muscle. It has been shown that MG53 not only plays important physiological roles but also acts as a crucial pathogenic factor of various diseases. First, MG53 preserves cardiac and skeletal muscle integrity via facilitating plasma membrane repair. Second, MG53 is essentially involved in cardiac ischemic preconditioning and postconditioning by activating PI3K-Akt-GSK3β and ERK1/2 cell survival signaling pathways. Moreover, systemic delivery of recombinant MG53 is able to abolish mechanic or ischemia-reperfusion (I/R)-induced injury of multiple organs, including heart, skeletal muscle, lung, kidney and skin. Importantly, MG53 acts as an E3 ligase to mediate the degradation of insulin receptor and insulin receptor substrate-1, and subsequently induces insulin resistance and metabolic diseases such as type-2 diabetes and its cardiovascular complications. In addition, MG53 negatively regulates myogenesis. As a potential therapeutic target of human diseases, multiple facets of MG53 biological function and mechanisms of
action should be taken into the consideration to maximize its beneficial effects and minimize potential side-effects. Here in this review, we intend to comprehensively summarize the current progresses on the biological functions of MG53, focusing on its clinical value as a therapeutic target.

Key words: MG53; ischemia/reperfusion injury; insulin resistance; lipid metabolism

Received: 2016-02-24　　Accepted: 2016-04-21

Corresponding author: 张岩　　E-mail: zhangyan9876@pku.edu.cn

Citing This Article：

ZHANG Yan, WU Hong-Kun, LV Feng-Xiang, XIAO Rui-Ping. MG53 is a double-edged sword for human diseases. Acta Physiol Sin 2016; 68 (4): 505-516 (in Chinese with English abstract).