The ubiquitin proteasome system (UPS) is the major nonlysosomal pathway for intracellular
protein degradation generally requiring a covalent linkage of one or more chains of polyubiquitins to the protein intended for degradation. It has become clear that the UPS plays major roles in regulating many cellular processes including the cell cycle, immune responses, apoptosis, cell signaling, and protein turnover under normal and pathologic conditions, as well as in protein quality control by removal of damaged, oxidized and/or misfolded proteins. This review will present an overview of the structure, biochemistry, and physiology of the UPS with emphasis on its
role in the
heart, if known. In addition,
evidence will be presented supporting the role of
certain muscle specific ubiquitin protein ligases, key regulatory components of the UPS, in regulation of sarcomere protein turnover and cardiomyocyte size and how this might play a role in induction of the hypertrophic phenotype. Moreover, this review will present the evidence suggesting that proteasomal dysfunction may play a role in cardiac pathologies such as myocardial ischemia, congestive heart failure, myofilament-related and idiopathic dilated cardiomyopathies, as well as cardiomyocyte loss in the aging heart. Finally, certain pitfalls of proteasome studies will be described with the intent of providing
investigators with enough information to avoid these problems. This review should
provide current investigators in the field with an up to date analysis of the literature and at the same time provide an impetus for new investigators to enter this important and rapidly changing area of research.