The ubiquitin-proteasome system: focus on the heart.
Proteasomes are the main non-lysosomal multicatalytic protease complexes that are involved in the degradation of most intracellular proteins. The substrate proteins are marked by ubiquitin, which serves as a tag for their regulated proteasomal destruction. One major function of the ubiquitin-proteasome system (UPS) is to prevent accumulation of non-functional, potentially toxic proteins. Moreover, it has become clear that the UPS is involved in most aspects of eukaryotic biology, such as intracellular signaling, transcriptional control, or regulation of cell death. Recent studies demonstrated that the UPS regulates receptor internalization, hypertrophic response, apoptosis, and tolerance to ischemia and reperfusion in cardiomyocytes. Since structural remodeling of the myocardium, ischemia-reperfusion injury, and myocardial cell loss are important components in the genesis of progressive heart failure, these findings suggest a pathophysiological role of the UPS. This review briefly summarizes present knowledge about structure and function of the proteasome in the heart and discusses the relevance of the UPS for cardiac diseases.
Zolk
Oliver
O
Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany. Zolk@pharmakologie-uni-erlangen.de
Schenke
Carolus
C
Sarikas
Antonio
A
D017209:Apoptosis; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex