Figure 1: Ubiquitin-proteasome system (UPS). UPS involves ubiquitination and proteolytic degradation of ubiquitinated proteins. Ubiquitin is first attached to the target protein via a cascade involving three distinct enzymes: ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). The ubiquitinated substrate is recognized, unfolded, and deubiquitinated by the 19S regulatory particle. The unfolded protein enters the 20S catalytic particle where it is degraded by the β1 (trypsin-like activity), β2 (caspase-like activity) and β5 (chymotrypsin-like activity) subunits.