Molecules and Cells

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Fig. 1.

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Fig. 1. (Left) General scheme of ubiquitin-proteasome system. An enzymatic cascade of E1-E2-E3 transfers ubiquitin to Lys residues on the substrate. As a consequence, the polyubiquitinated substrate is recognized by the 26S proteasome and undergoes degradation. (Right) Induced proteolysis by PROTAC and/or DUB inhibitor. PROTAC links E3 and the target protein, enhances E3-mediated ubiquitination, and promotes degradation of the target molecule. By contrast, DUBs acting upstream of the proteasome (violet) or on the proteasome (olive drab) can inhibit degradation through substrate deubiquitination. Therefore, DUB inhibitors may facilitate the proteasomal degradation pathway by antagonizing deubiquitination.
Mol. Cells 2018;41:933~942
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