The role of ubiquitin ligases in cardiac disease

• Published in: Journal of molecular and cellular cardiology Vol. 71; pp. 43 - 53
• Main Authors: Willis, Monte S, Bevilacqua, Ariana, Pulinilkunnil, Thomas, Kienesberger, Petra, Tannu, Manasi, Patterson, Cam
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2014
• Subjects: Animals; Cardiac; Cardiomyopathy; Cardiovascular; Heart Diseases - enzymology; Heart Diseases - metabolism; Heart failure; Humans; Ischemic heart disease; Myocytes, Cardiac - enzymology; Myocytes, Cardiac - metabolism; Proteasome; Proteasome Endopeptidase Complex - metabolism; Ubiquitin - metabolism; Ubiquitin ligase; Ubiquitin-Protein Ligases - metabolism; ubiquitin ligase; Fbxl22; ubiquitin-protein ligase E3A; Cardiomyopathy; outer mitochondrial membrane; optic atrophy 1; PTEN-induced putative kinase protein 1; Mfn-1 (-2); E1; E2; E3; cavelin 3; Opa1; Siah1a/2; AKAP121; UBE3A/E6AP; Proteasome; Heart failure; ubiquitin-conjugating enzyme; Cardiac; dynamin-1-like protein; atrogin-1/muscle atrophy F-box; human ether-à-go-go-related gene; A-kinase anchor protein 121; cellular inhibitor of apoptosis; OMM; mitofusin-1 (-2); seven in absentia homolog-1a/2; cardiac myosin binding protein C; cMyBP-C; ubiquitin-activating enzyme; Nedd4-2; Drp1; Ischemic heart disease; Casitas b-lineage lymphoma; CHIP; fission 1; AChRs; cIAP; muscle ring finger-1 (-2, -3); Fis1; hERG; Cav3; murine double minute 2; acetylcholine receptors; c-Cbl; PINK1; F-box and leucine-rich repeat protein 22; MAFBx; c-terminus of Hsp70-interacting protein; MDM2; neural precursor cell expressed developmentally down-regulated protein 4-2; MuRF1(2,3); Ubiquitin ligase
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2013.11.008

Abstract Rigorous surveillance of protein quality control is essential for the maintenance of normal cardiac function, while the dysregulation of protein turnover is present in a diverse array of common cardiac diseases. Central to the protein quality control found in all cells is the ubiquitin proteasome system (UPS). The UPS plays a critical role in protein trafficking, cellular signaling, and most prominently, protein degradation. As ubiquitin ligases (E3s) control the specificity of the UPS, their description in the cardiomyocyte has highlighted how ubiquitin ligases are critical to the turnover and function of the sarcomere complex, responsible for the heart's required continuous contraction. In this review, we provide an overview of the UPS, highlighting a comprehensive overview of the cardiac ubiquitin ligases identified to date. We then focus on recent studies of new cardiac ubiquitin ligases outlining their novel roles in protein turnover, cellular signaling, and the regulation of mitochondrial dynamics and receptor turnover in the pathophysiology of cardiac hypertrophy, cardiac atrophy, myocardial infarction, and heart failure. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".