The ubiquitin-mediated system for intracellular protein degradation

Degradation of proteins by the ubiquitin system involves several discrete steps. Initially, multiple molecules of ubiquitin are covalently conjugated to the target substrate in an energy-requiring reaction. The protein thus marked is degraded by a specific ATP-dependent protease, and free and reutilizable ubiquitin is released. In this review we discuss the mechanisms involved in ubiquitin activation, selection of substrates for conjugation, and subsequent degradation of ubiquitin-conjugated proteins in the cell-free system. In addition, we summarize briefly what is currently known of the physiological roles of the ubiquitin system in vivo.