MG-132 is a cell-permeable, potent, and reversible proteasome inhibitor (Ki = 4 nM). Reduces degradation of ubiquitin-conjugated proteins in mammalian cells and permeable strains of yeast by the 26S complex without affecting its ATPase or isopeptidase activities. Activates c-Jun N-terminal kinase (JNK1), which initiates apoptosis. Inhibits NF-kB activation (IC₅₀ = 3 µM). Prevents γ-secretase cleavage.