Figure 1

Summary of the ubiquitin system and possible intervention nodes. Ubiquitination is an ATP-dependent process carried out by three classes of enzymes. E1 activating enzymes form a thioester bond with ubiquitin, followed by subsequent binding of ubiquitin to E2 conjugating enzymes, and ultimately the formation of an isopeptide bond between the carboxyl-terminal glycine of ubiquitin and a lysine residue on the substrate protein, which requires E3 ubiquitin ligases. Multiple intervention nodes in the reaction cascade have been proposed to either block or enhance ubiquitination.