MG132 is a specific, potent, reversible, and cell-permeable proteasome inhibitor

Proteasome inhibitor

Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins, like the p53 protein. Proteasome inhibitors are being studied in the treatment of cancer.-Examples:...

 (Ki

KI

Ki or KI may refer to:* .ki, the ISO 3166-1 alpha-2 country code top level domain for Kiribati*Ki., an abbreviation for the Book of Kings in Judaeo-Christian religious texts* Ki * Ki , a Japanese syllabic character...

 = 4 nM)
. Reduces the degradation of ubiquitin

Ubiquitin

Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

-conjugated proteins in mammalian cells and permeable strains of yeast by the 26S complex without affecting its ATPase

ATPase

ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

 or isopeptidase activities. MG132 activates c-Jun N-terminal kinase (JNK1), which initiates apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

. MG132 also inhibits NF-κB activation with an IC50 of 3 µM and prevents β-secretase

Beta-secretase

Beta-secretase 1 also known as beta-site APP cleaving enzyme 1 , memapsin-2 , and aspartyl protease 2 is an enzyme that in humans is encoded by the BACE1 gene.β-Secretase is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease,...

cleavage.