Figure 1. The ubiquitin-proteasome pathway.

Prior to proteasome degradation, target proteins are flagged with polyubiquitin chain transferred by ubiquitination system through interaction of the ubiquitin-activating enzyme E1, the ubiquitin-conjugating enzyme E2, and the ubiquitin ligase E3. Target proteins with polyubiquitin tag could be recognized by the 19S regulatory complex of the proteasome and fed into the 20S catalytic core, which has four stacked rings in αββα order. Each of the inner β rings contains seven β subunits with catalytic site facing the central cavity. Each of the outer α rings contains seven α subunits that serve as a gate for protein entry into the inner catalytic site.