Figure 1

The ubiquitin proteasome system. In step 1, ubiquitin is activated by a ubiquitin activating enzyme, E1. In step 2, activated ubiquitin is transferred to a ubiquitin conjugating enzyme, E2. In step 3, ubiquitin is subsequently conjugated to target proteins in a process mediated by an E3 ubiquitin ligase. In step 4, the polyubiquitylated substrate protein is degraded by the 26S proteasome. A single E1 enzyme can transfer ubiquitin to all of the E2s in the cell, and each of the E2s associates with a restricted set of E3s that confer substrate specificity.