Ubiquitin-Proteasome Pathway and Muscle Atrophy

Many systemic diseases are featured by muscle atrophy. Cellular proteins are modified by covalent attachment to a small protein known as ubiquitin (Ub) through ubiquitination. This ubiquitination process serves as signal for protein turnover that leads to rapid muscle mass lack. This process is carried out through an enzymatic cascade, which includes three groups of enzymes termed ubiquitin E1 (activating enzyme), ubiquitin E2 (conjugating enzyme), and ubiquitin E3 (ligase). There are several ways of ubiquitin conjugation driving to ubiquitination of specific proteins through ubiquitin-proteasome system (UPS). A lot of UPS genes stated to be included in skeletal muscle atrophy. These genes do their effects by modifying different processes which affect muscle mass including myofibrillar protein degradation, myogenesis inhibition, and even modulation of autophagy as well as upstream regulatory pathways.