Figure 3.

The ubiquitin enzymatic cascade and the ubiquitin-proteasome system (USP). (1) A diagram of the ubiquitin enzymatic cascade. Ubiquitin is added to protein substrates via the E1-E2-E3 enzymatic cascade; (A) E1 activating enzymes, which catalyze the addition of ubiquitin to E1 enzymes is ATP-dependent [39]; (B) E2 conjugating enzymes; (C) E3 ligases, which catalyze the addition of ubiquitin to protein substrates and (D) deubiquitinases, which catalyze the removal of ubiquitin from protein substrates. The addition of ubiquitin to protein substrates can have serval consequences, including (2) the modulation of signal transduction or protein recruitment and localization or (3) proteasomal degradation, which requires ATP. Highlighted in red are components of the ubiquitin system that have been targeted with small molecule inhibitors and are discussed in this review.