Identification of ubiquitin ligases required for skeletal muscle atrophy

Skeletal muscle adapts to decreases in activity and load by undergoing atro phy. To identify candidate molecular mediators of muscle atrophy, we perfor med transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy mod els. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuR F1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFb x in myotubes produced atrophy, whereas mice deficient in either MAFbx or M uRF1 were found to be resistant to atrophy. These proteins are potential dr ug targets for the treatment of muscle atrophy.