In eukaryotes, proteasomes play a critical role in the degradation of most intracellular proteins.[1–4] Degradation by ubiquitin-proteasome pathway controls many fundamental cellular functions. These include cell differentiation, cell-cycle regulation, signal transduction pathways, antigen processing in immune responses, stress signaling, inflammatory responses, and apoptosis. The first step in the pathway is activation of ubiquitin-activating ...