The Pivotal Role of Mitsugumin 53 in Cardiovascular Diseases
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The Pivotal Role of Mitsugumin 53 in Cardiovascular Diseases Wenhua Jiang1 · Manling Liu2 · Chunhu Gu3 · Heng Ma1 Received: 11 June 2020 / Accepted: 23 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The MG53 (also known as TRIM72) is a conserved, muscle-specific tripartite motif family protein that is abundantly expressed in cardiac or skeletal muscle and present in circulation. Recently, the MG53 had been hypothesized to serve a dual role in the heart: involving in repairing cell membranes that protect myocardial function while acting as an E3 ligase to trigger insulin resistance and cardiovascular complications. This review discusses the roles of MG53 in cardiac physiological function with emphasis on MG53 protective function in the heart and its negative impact on the myocardium due to the continuous elevation of MG53. Besides, this work reviewed the significance of MG53 as a potential therapeutic in human cardiovascular diseases. Despite the expression of MG53 being rare in the human, thus exogenous MG53 can potentially be a new treatment for human cardiovascular diseases. Notably, the specific mechanism of MG53 in cardiovascular diseases remains elusive. Keywords MG53 · Cardiovascular diseases · Insulin resistance · Ischemic cardiomyopathy
Introduction Mitsugumin 53 (MG53), also called TRIM72, is a striated muscle-specific in tripartite motif (TRIM) family protein. The TRIM protein family contains a relatively conservative RBCC motif that includes a RING domain for E3 ubiquitin ligase activity, a zinc-binding b-box for protein–protein interactions, and a predicted coiled-coil region for oligomerization. As a distinct within the TRIM family, the MG53 protein carboxyl terminus has the PRY/SPRY domain [1–4]. The MG53 is a soluble and monomer protein [5, 6] having 477 amino acids with a molecular weight of 53 kDa and Handling Editor: Martin Štěrba. * Chunhu Gu [email protected] * Heng Ma [email protected] 1
Institute of Medical Research, Northweastern Polytechnical University, Xi’an 710072, People’s Republic of China
2
Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, People’s Republic of China
3
Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, People’s Republic of China
is expressed in myocardium sarcolemma and skeletal muscle sarcolemma [7]. Precisely as demonstrated in quantitative immunoassay studies, the MG53 expresses in lysates of kidney and lung tissue account for 2.5% and about 5% of that in skeletal muscle, respectively [8, 9]. Studies have shown that MG53 is connected to intracellular vesicles that are transported among different subcellular compartments [10]. Besides participating in intracellular vesicle transport [11], MG53 is also involved in the processes of acute repair after cell injury [8, 9, 12], cardioprotection [13], skeletal muscle differentiation [7, 14] and skeletal myogenesis [15]. Circulating MG
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