Product Feature - Proteasome and NF-κB

The proteasome is a large barrel-like protein located in the cytoplasm and nucleus of eukaryotic cells. The most common form is the 26S proteasome which consists of one 20S core particle and two regulatory caps (11S or 19S). The 20S core particle is a hollow, enclosed cavity that contains protease active sites. The main function of the proteasome is to degrade unneeded and damaged proteins by proteolysis. Proteins are targeted to the proteasome by the covalent modification of lysine residues with a polyubiquitin chain; a process called ubiquitination. Ubiquitinated proteins are targeted to the 19S regulatory cap where the degradation process can begin. The proteasomal degradation pathway is involved in many cellular processes including the cell cycle, gene expression and responses to oxidative stress.

The proteasome plays an important role in the regulation of NF-κB. In the inactivated state, NF-κB is located in the cytoplasm bound by the inhibitory peptide IκB. Following phosphorylation by IκB kinase (IKK), IκB is ubiquitinated and targeted to the proteasome for degradation. NF-κB is now free to enter the nucleus where it can regulate gene expression.

Key proteasome inhibitors now available from Tocris include:

20S proteasome inhibitor
2564 l AM 114
Displays anticancer activity; inhibits cell growth in human colon cancer HCT116 p53+/+ cells (IC₅₀ = 1.49 μM).

Proteasome and calpain inhibitor
1748 l MG 132
Inhibits TNF-α-induced NF-κB activation and IκBα degradation.

Potent and selective proteasome inhibitor
2267 l Lactacystin
Binds irreversibly to the active site N-terminal threonine residue of the catalytic β-subunit of the 20S proteasome, thereby inhibiting its chymotrypsin and trypsin-like activities. Inhibits NF-κB activation (IC₅₀ = 10 μM).

Inhibitor of 20S proteasome
2637 l Gliotoxin
Non-competitively inhibits chymotrypsin-like activity of 20S proteasome; prevents degradation of IκBα, an endogenous blocker of NF-κB.

View all Proteasome and NF-κB Related Products

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