Eureka! Institutional Repository

The skeletal muscle accounts for almost 40% of total body mass and represents a major site of metabolic activity. Skeletal muscle is a dynamic tissue: exercise and hormonal stimulation lead to an increase in protein synthesis and fiber size, a process called hypertrophy. Conversely, the loss of muscle mass, named atrophy, is the result of an increase in protein degradation. Muscle atrophy can occur in several pathological conditions like cancer, diabetes, chronic heart failure, AIDS, and during aging. Atrophy is an active process controlled by specific signaling pathways and transcriptional programs but the identification of the precise signaling cascades that direct muscle wasting remains poorly understood. The Ubiquitin Proteasome System (UPS) is one of the major mechanisms that control proteolysis and ubiquitination of protein substrates. The specificity of ubiquitin-dependent degradation derives from many E3s that recognize specific substrates. This work is interested in the study of the role of Asb2β in vivo, a new E3 muscle-specific ubiquitin ligase. To understand its role, we generated skeletal muscle specific knock-out mouse models and we analyzed its function in physiological and in muscle wasting conditions. Furthermore, characterization of different E3s and their respective substrates in skeletal muscle could represent an important step to understand the mechanisms that control muscle mass loss and, moreover, to develop targets for pharmacological intervention in muscle disease