MG-132

26S proteasome inhibitor

26S proteasome inhibition by MG-132

MG-132 is a peptide aldehyde (Z-Leu-Leu-Leu-al) that selectively blocks the proteolytic activity of the 26S proteasome. The 26S proteasome is a large protease complex that degrades ubiquitinated proteins into smaller peptides. It plays a central role in the regulation of proteins that control cell-cycle progression and apoptosis.

 More details

Mode of action:

MG-132 reduces the degradation of ubiquitin-conjugated proteins in mammalian cells by the 26S proteasome. This potent inhibitor is used as a tool for disrupting the proteasome-regulated degradation of intracellular proteins, such as IκB. Inhibition of IκB proteasomal degradation by MG-132 leads to the suppression of NF-κB activation [1].
Of note, studies suggest that inhibition of the 26S proteasome by MG-132 can induce autophagy by stabilizing Atg protein levels [2].

Key features:

• A potent inhibitor of the 26S proteasome
• An autophagy inducer
• InvitroFit™ grade: each lot is functionally tested

References

1. Lee DH, Goldberg A.L., 1998. Proteasome inhibitors: valuable new tools for cell biologists. Trends Cell Biol. 8(10):397-403.
2. Ge PF. et al., 2009. Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells. Acta Pharmacol Sin. 30(7):1046-52.

Figures

MG-132 is a potent inhibitor of the 26S proteasome.
RAW-Blue™ cells were incubated overnight at 37°C in the presence of increasing concentrations of MG-132 together with 1 μg/ml of Pam3CSK4. The next day, the inhibitory activity of MG-132 was determined by measuring the reduction of SEAP production in the supernatant using the QUANTI‑Blue™ Solution detection reagent. Data are shown as percentage (%) inhibition. 

Specifications

Working concentration: 200 ng/ml - 20 µg/ml (420 nM - 42 µM)

CAS number: 133407-82-6

Synonym: Z-Leu-Leu-Leu-al

Formula: C₂₆H₄₁N₃O₅

Molecular weight: 475.62 g/mol

Solubility: 20 mg/ml in DMSO

Quality control:

• The inhibitory activity has been validated using cellular assays.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) is confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Contents

• 2 x 5 mg MG-132

MG-132 is shipped at room temperature.

 Upon receipt, store at -20°C.

Details

26S proteasome

The 26S proteasome is a large, ∼2.5 MDa, multi-catalytic ATP-dependent protease complex [1, 2]. It is responsible for the degradation of cytosolic, nuclear, and membrane proteins in eukaryotic cells, which are targeted for degradation via polyubiquitination. Proteasome-mediated degradation plays a crucial role in maintaining cell integrity by eliminating misfolded and damaged proteins. Proteasome-dependent proteolysis is also essential to regulate a number of other cellular processes, such as cell differentiation, cell-cycle progression, or apoptosis. Proteins targeted for degradation are allowed inside the proteasome particle, where they are cleaved into small peptides and released in the cytosol to be degraded into amino acids. This amino acid pool is used for the synthesis of proteins and other nitrogen-containing compounds such as DNA bases, neurotransmitters, and hormones.

References:

1. Livneh I. et al., 2016. The life cycle of the 26S proteasome: from birth, through regulation and function, and onto its death. Cell Res . 2016 Aug;26(8):869-85.
2. Adams J., 2003. The proteasome: structure, function, and role in the cell. Cancer Treat Rev .29 Suppl 1:3-9.

Chemical structure of MG-132: