The ubiquitin-proteasome system and skeletal muscle wasting

• Published in: Essays in biochemistry Vol. 41; p. 173
• Main Authors: Attaix, Didier, Ventadour, Sophie, Codran, Audrey, Béchet, Daniel, Taillandier, Daniel, Combaret, Lydie
• Format: Journal Article
• Language: English
• Published: England 01.01.2005
• Subjects: Animals; Humans; Multienzyme Complexes - metabolism; Muscle Proteins - metabolism; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscular Atrophy - metabolism; Peptide Hydrolases - metabolism; Proteasome Endopeptidase Complex - biosynthesis; Proteasome Endopeptidase Complex - metabolism; Signal Transduction; SKP Cullin F-Box Protein Ligases - metabolism; Tripartite Motif Proteins; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - metabolism; Up-Regulation
• ISSN: 0071-1365
• DOI: 10.1042/eb0410173

The ubiquitin-proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin-protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.