Ubiquitin Proteasome System (UPS)

Protein degradation is a regulated, multistep process. Ubiquitin is loaded onto E1-activating enzymes in an ATP-dependent manner and then transferred to E2-binding enzymes. The same E2 can bind to many E3 ligases, which in turn can ubiquitinatemultiple target substrate proteins. E3 ligases bind specific substrate proteins based on substrate degronmotifs. Sorting, lysosomal disruption, or proteolytic cleavage and degradation by the 26S ubiquitin proteasome by different labeling of K48 residues on substrate-bound Ubs. DUBs deubiquitinasescatalyze the removal of Ub and regulate Ub-mediated pathways.