The selective degradation of many short-lived proteins in eukaryotic cells is carried out by the ubiquitin-mediated proteolytic system.In this pathway,proteins are targeted for degradation by covalent ligation to ubiquitin,a highly conserved small protein.The ligation of ubiquitin to protein involves the successive action of three types of enzymes:the ubiquitin-activating enzyme E 1,a ubiquitin-carrier protein E2 and a ubiquitin-protein ligase,E3.The selectivity and the regulation of the degradation of a specific protein are usually determined by the properties of its specific ubiquitin ligase (E3) enzyme.We have been studying two ubiquitin ligase complexes that have important roles in different aspects of cell cycle regulation.