Figure 2.

The UPS. The UPS functions as an ATP-dependent proteolytic system that requires polyubiquitination via lysine 48 residues of the target protein prior to its degradation by the 26S proteasome. Polyubiquitination involves the concerted action of three enzymes: E1 (ubiquitin-activating), E2 (ubiquitin-conjugating), and E3 (ubiquitin ligase), the latter affording substrate specificity. The eukaryotic 26S proteasome is a large, multicatalytic protein complex composed of the 19S regulatory complex and the 20S proteasome. The damaged, misfolded, or mutant proteins are degraded by three major peptidase activities (chymotrypsin-like, trypsin-like, and caspase-like).