MG53 (also known as TRIM72) is a cardiac and skeletal muscle-specific TRIM-family protein that exhibits multiple biological 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, pre-conditioning and post-conditioning, by activating the PI3K-Akt-GSK3β and ERK1/2 survival signaling pathways. Moreover, systemic delivery of recombinant MG53 protein ameliorates the impact of a range of injury insults on 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 physiological and pathological processes of multiple organs, and is a promising therapeutic target for various human diseases. In this review, we intend to comprehensively summarize current research progress on the biological functions and therapeutic potential of MG53.
- The American Society for Pharmacology and Experimental Therapeutics