Atrogin-1 is a muscle-specific F-box protein highly expressed during muscle atrophy. Researchers identified this gene using cDNA microarrays, finding that it is induced more than ninefold in fasted mice. Atrogin-1 is specifically expressed in striated muscles and increases in muscles atrophying due to diabetes, cancer, and renal failure. It contains a functional F-box domain that binds to Skp1, Cul1, and Roc1, components of the SCF-type ubiquitin-proteasome pathway, as well as a nuclear localization sequence and PDZ-binding domain. Atrogin-1 mRNA levels increase specifically in skeletal muscle before atrophy occurs, suggesting its role in the enhanced proteolysis leading to muscle atrophy. In mammals, muscle protein serves as a primary reserve of amino acids mobilized during fasting and disease. Muscle atrophy during fasting and systemic diseases like diabetes, cancer, and uremia is characterized by increased protein breakdown via the ubiquitin-proteasome pathway. Atrogin-1 is one of the few F-box proteins or ubiquitin-protein ligases (E3s) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy. Atrogin-1 is an F-box protein and a component of the SCF E3 complex. It contains a functional F-box domain that binds to Skp1, and its expression is increased in various models of muscle atrophy, including fasting, diabetes, cancer, and uremia. Atrogin-1 is expressed in striated muscles and is involved in the ubiquitination of proteins, contributing to muscle atrophy. The study shows that atrogin-1 is a muscle-specific gene whose expression is upregulated in diverse conditions of muscle wasting. The findings suggest that atrogin-1 plays a key role in the initiation and maintenance of accelerated proteolysis during muscle atrophy.Atrogin-1 is a muscle-specific F-box protein highly expressed during muscle atrophy. Researchers identified this gene using cDNA microarrays, finding that it is induced more than ninefold in fasted mice. Atrogin-1 is specifically expressed in striated muscles and increases in muscles atrophying due to diabetes, cancer, and renal failure. It contains a functional F-box domain that binds to Skp1, Cul1, and Roc1, components of the SCF-type ubiquitin-proteasome pathway, as well as a nuclear localization sequence and PDZ-binding domain. Atrogin-1 mRNA levels increase specifically in skeletal muscle before atrophy occurs, suggesting its role in the enhanced proteolysis leading to muscle atrophy. In mammals, muscle protein serves as a primary reserve of amino acids mobilized during fasting and disease. Muscle atrophy during fasting and systemic diseases like diabetes, cancer, and uremia is characterized by increased protein breakdown via the ubiquitin-proteasome pathway. Atrogin-1 is one of the few F-box proteins or ubiquitin-protein ligases (E3s) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy. Atrogin-1 is an F-box protein and a component of the SCF E3 complex. It contains a functional F-box domain that binds to Skp1, and its expression is increased in various models of muscle atrophy, including fasting, diabetes, cancer, and uremia. Atrogin-1 is expressed in striated muscles and is involved in the ubiquitination of proteins, contributing to muscle atrophy. The study shows that atrogin-1 is a muscle-specific gene whose expression is upregulated in diverse conditions of muscle wasting. The findings suggest that atrogin-1 plays a key role in the initiation and maintenance of accelerated proteolysis during muscle atrophy.