A systematic view on E3 ligase Ring TRIMmers with a focus on cardiac function and disease.

Ubiquitination, a post-translational modification via ubiquitin-proteasome-system, is one of the vital cellular processes involved in intracellular signaling, cell death, transcriptional control, etc. Importantly, it prevents the aggregation of non-functional, misfolded or unfolded, potentially toxic proteins to maintain cellular protein homeostasis. Ubiquitination is accomplished by the concerted action of three enzymatic steps involving E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. Tripartite motif-containing (TRIM) proteins are one of the integral members of E3 ubiquitin ligases in metazoans modulating essential cellular pathways. For long, MuRFs (Muscle ring finger proteins) were the most extensively studied TRIMs for their cardiac function. Recent research advances in the field and our analysis presented here, however, demonstrated broader and ever increasing involvement of additional TRIM E3 ligases in the pathophysiology of heart. In this review, we summarize the known cardiac E3 ligases and their targets, and discuss their role and importance in cardiac proteostasis, pathophysiology and potential therapeutic implications with specific focus on TRIM E3 ligases.