RESEARCH ti a

The protein turnover represents a finely regulated bal-ance between protein synthesis and degradation. Many regulatory proteins have very short half-time and are rapidly hydrolyzed to their constituent amino acids and replaced by newly synthesized proteins. In mammalian tissues, proteins are degraded mainly by the ubiquitin-proteasome system (UPS) [1,2]. The UPS is part of all eukaryotic cells and involves a complex cascade of enzymes and displays a high degree of specificity to-wards its numerous substrates [3]. The tagging process, which involves the linking of ubiquitin chain to proteins via an isopeptide bond, is the rate limiting process me-diated by three enzymatic steps. First, ubiquitin is bound via its carboxyl terminus to the sulfhydryl group of ubiquitin-activating enzyme (E1). Thereafter, ubiqui-tin is transferred from E1 to ubiquitin-conjugating en-zyme (E2), via formation a high energy thioester linkage [4]. In the last step, the specific ubiquitin-ligase en-zymes (E3), in skeletal muscle mainly muscle RING * Correspondence