The ubiquitin-proteasome system in cardiac proteinopathy: A quality control perspective

Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Lee Medical Building, 414 E Clark Street, Vermillion, SD 57069, USA.
Cardiovascular Research (Impact Factor: 5.94). 09/2009; 85(2):253-62. DOI: 10.1093/cvr/cvp287
Source: PubMed


Protein quality control (PQC) depends on elegant collaboration between molecular chaperones and targeted proteolysis in the cell. The latter is primarily carried out by the ubiquitin-proteasome system, but recent advances in this area of research suggest a supplementary role for the autophagy-lysosomal pathway in PQC-related proteolysis. The (patho)physiological significance of PQC in the heart is best illustrated in cardiac proteinopathy, which belongs to a family of cardiac diseases caused by expression of aggregation-prone proteins in cardiomyocytes. Cardiac proteasome functional insufficiency (PFI) is best studied in desmin-related cardiomyopathy, a bona fide cardiac proteinopathy. Emerging evidence suggests that many common forms of cardiomyopathy may belong to proteinopathy. This review focuses on examining current evidence, as it relates to the hypothesis that PFI impairs PQC in cardiomyocytes and contributes to the progression of cardiac proteinopathies to heart failure.

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Available from: Xuejun Wang, Jun 03, 2015
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    • "Proteinopathies are diseases that are characterized by protein misfolding and aggregation, including desmin-related cardiomyopathy (DRC) [280] [281]. Proteasome function insufficiency is observed in a variety of heart diseases [282] [283] in animals, i.e. myocardial ischemia/ reperfusion (I/R) injury and pressure overload-induced cardiomyopathy [281] [284] [285], as well as in humans, i.e. hypertrophic or dilated cardiomyopathy [283] [286]. Cardiomyocyte-restricted overexpression of the proteasome 28 subunit α (CR-PA28αOE) in mice caused augmentation of cardiac UPS proteolytic function. "
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