Emerging Role of TRIM Family Proteins in Cardiovascular Disease

Abstract

Ubiquitination is one of the basic mechanisms of cell protein homeostasis and degradation and is accomplished by 3 enzymes, E1, E2, and E3. Tripartite motif-containing proteins (TRIMs) constitute the largest subfamily of RING E3 ligases, with > 70 current members in humans and mice. These members are involved in multiple biological processes, including growth, differentiation, and apoptosis as well as disease and tumorigenesis. Accumulating evidence has shown that many TRIM proteins are associated with various cardiac processes and pathologies, such as heart development, signal transduction, protein degradation, autophagy mediation, ion channel regulation, congenital heart disease, and cardiomyopathies. In this review, we provide an overview of the TRIM family and discuss its involvement in the regulation of cardiac proteostasis and pathophysiology and its potential therapeutic implications.

Emerging Roles of TRIM Family Proteins in Gliomas Pathogenesis

“…Finally, it is worth noting that various TRIM proteins have been implicated in metabolic disorders, ranging from obesity (i.e., TRIM23, TRIM25, TRIM28, and TRIM67) [ 51 , 52 ] to diabetes (i.e., TRIM7, TRIM27, TRIM32, and TRIM72), [ 53 ] as well as cardiovascular diseases [ 54 ]. The muscle-specific TRIM called Mitsugumin 53 (MG53 or TRIM72) is leading research attention in this field, and it has been shown to negatively regulate myogenesis and promote diabetic as well as cardiovascular complications.…”

Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway

“…Functional studies have demonstrated that different TRIMs, such as TRIM8, TRIM10, TRIM21, TRIM24, TRIM28, TRIM32, TRIM37, TRIM45, TRIM50, TRIM67, TRIM72 and TRIM76, have distinct effects on cardiac function and cardiac pathology, and are involved in cardiomyocyte apoptosis, ischemia–reperfusion injury, myocardial dysplasia and cardiomyopathy ( Yang et al, 2020 ; Chen et al, 2017 , 2012 ; Heliste et al, 2020 ; Borlepawar et al, 2019 ; Gupta et al, 2018 ; Brigant et al, 2018 ; Zhang et al, 2020 ; Rabinovich-Nikitin and Kirshenbaum, 2019 ; Zhang et al, 2021 ). Given the complexity of cardiac physiology and pathology, few TRIMs have been shown to have effects on the cardiovascular system.…”

Structural studies of the coiled-coil domain of TRIM75 reveal a tetramer architecture facilitating its E3 ligase complex

“…They play crucial roles in various physiological and pathological processes including DNA repair, apoptosis, autophagy, innate immunity, cell proliferation and development, and carcinogenesis [7] , [8] , [9] . Their dysregulation causes various diseases including cancer, infectious inflammatory, cardiovascular diseases, and neuropsychiatric disorders [10] , [11] , [12] . TRIM proteins usually consist of a conserved N -terminal tripartite motif: RING domain, B box (B box1 and/or B box 2), and coiled-coil domain, and a diverse C-terminal domain that determines substrate specificity.…”