Zhang Yan, Wu Hong-Kun, Lv Fengxiang, Xiao Rui-Ping
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (Y.Z., H.-K.W., F.L., R.-P.X.), Peking-Tsinghua Center for Life Sciences (R.-P.X.), and Beijing City Key Laboratory of Cardiometabolic Molecular Medicine (R.-P.X.), Peking University, Beijing, China
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (Y.Z., H.-K.W., F.L., R.-P.X.), Peking-Tsinghua Center for Life Sciences (R.-P.X.), and Beijing City Key Laboratory of Cardiometabolic Molecular Medicine (R.-P.X.), Peking University, Beijing, China.
Mol Pharmacol. 2017 Sep;92(3):211-218. doi: 10.1124/mol.117.108241. Epub 2017 Apr 21.
MG53 (also known as tripartite motif, TRIM72) is a cardiac and skeletal muscle-specific TRIM-family protein that exhibits multiple biologic functions. First, MG53 participates in plasma membrane repair of the heart, skeletal muscle, and, other tissues. Second, MG53 is essentially involved in the cardioprotection of cardiac ischemic, preconditioning, and postconditioning by activating the PI3K-Akt-GSK3 and ERK1/2 survival signaling pathways. Moreover, systemic delivery of recombinant MG53 protein ameliorates the impact of a range of injury insults on the heart, skeletal muscle, lung, kidney, skin, and brain. It is noteworthy that chronic upregulation of MG53 induces insulin resistance and metabolic diseases, such as type 2 diabetes and its cardiovascular complications, by acting as an E3 ligase to mediate the degradation of insulin receptor and insulin receptor substrate-1. In addition, MG53 negatively regulates myogenesis. In summary, MG53 is a multifunctional protein involved in the vital physiologic and pathologic processes of multiple organs and is a promising therapeutic target for various human diseases. In this review, we comprehensively summarize current research progress on the biologic functions and therapeutic potential of MG53.
MG53（也称为三联基序，TRIM72）是一种心肌和骨骼肌特异性的TRIM家族蛋白，具有多种生物学功能。首先，MG53参与心脏、骨骼肌和其他组织的质膜修复。其次，MG53通过激活PI3K-Akt-GSK3和ERK1/2存活信号通路，在心脏缺血预处理和后处理的心脏保护中发挥重要作用。此外，重组MG53蛋白的全身递送可减轻一系列损伤对心脏、骨骼肌、肺、肾、皮肤和大脑的影响。值得注意的是，MG53的长期上调通过作为E3连接酶介导胰岛素受体和胰岛素受体底物-1的降解，诱导胰岛素抵抗和代谢疾病，如2型糖尿病及其心血管并发症。此外，MG53对肌生成起负调节作用。总之，MG53是一种多功能蛋白，参与多个器官的重要生理和病理过程，是多种人类疾病有前景的治疗靶点。在本综述中，我们全面总结了目前关于MG53生物学功能和治疗潜力的研究进展。
