title: Protein turnover in cardiac cell growth and survival.
abstract: Protein turnover represents the balance between protein synthesis and degradation. It can be controlled quantitatively, for instance by an activation of protein synthesis during cardiac hypertrophy or by activating protein degradation during ventricular unloading. It can also be regulated qualitatively by changing the steady state concentration of specific proteins and enzymes. The recent literature points to an emerging role for the mammalian target of rapamycin (mTOR) and for the ubiquitin-proteasome system (UPS) in this process, and both pathways interact in the regulation of cell growth and survival. We highlight the critical role played by such interaction in different cellular functions, including insulin signaling, stress response to hypoxia, adaptation to variations in workload, regulation of protein phosphatase activity, apoptosis and post-ischemic recovery. A deregulation of these pathways participates in the mechanisms of cardiac ischemia, hypertrophy and failure, and controlling their activity represents an opportunity for novel therapeutic avenues.
authors.affiliation: Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark, 07103, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Hedhli
authors.forename: Michel
authors.initials: M
authors.lastname: Pelat
authors.forename: Christophe
authors.initials: C
authors.lastname: Depre
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D020123:Sirolimus