title: The role of ubiquitin ligases in cardiac disease.
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".
authors.affiliation: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: monte_willis@med.unc.edu.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Ariana
authors.initials: A
authors.lastname: Bevilacqua
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalhousie University, Saint John, NB, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalhousie University, Saint John, NB, Canada.
authors.forename: Petra
authors.initials: P
authors.lastname: Kienesberger
authors.affiliation: College of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Manasi
authors.initials: M
authors.lastname: Tannu
authors.affiliation: Departments of Cell and Developmental Biology, Medicine (Cardiology), and Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
mesh_terms: D000818:Animals; D006331:Heart Diseases / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Cardiac; Cardiomyopathy; Heart failure; Ischemic heart disease; Proteasome; Ubiquitin ligase