Figure 1.

Ubiquitylation cascade. Ubiquitylation of substrates requires a cascade of events involving three enzymes: an E1 ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and an E3 ubiquitin ligase. First in this cascade, the E1 enzyme activates ubiquitin and transfers it to the E2 enzyme in an ATP-dependent manner with which ubiquitin is conjugated. Afterward, the ubiquitin molecule is transferred from the E2 enzyme to the specific target substrate by the E3 ligase enzymes, which either actively receives ubiquitin from E2 and then transfers it to the substrate or serves as a binding platform between the E2 and the substrate. Finally, on the target substrate, mono, mono-multi, or polyubiquitylation can occur.