Proteasome subunit beta type-6 and type-7 (PSMB6 and PSMB7)

The proteasome beta catalytic subunits β1 and β2 (encoded by the PSMB6 and PSMB7 genes, respectively) are essential components of the 20S core particle of the 26S proteasome, which is the primary machinery for regulated protein degradation in eukaryotic cells. Subunit β1 is responsible for caspase-like (post-acidic) proteolytic activity, while subunit β2 provides trypsin-like (post-basic) activity. Together with the β5 subunit, they form the internal catalytic chamber where ubiquitinated proteins are hydrolyzed into short peptides, a process vital for maintaining protein homeostasis, regulating the cell cycle, and facilitating MHC class I antigen presentation. In malignant conditions such as multiple myeloma and mantle cell lymphoma, cells exhibit a high rate of protein synthesis and a heightened dependency on proteasome-mediated degradation to prevent the accumulation of toxic misfolded proteins. Therapeutic targeting of these subunits with proteasome inhibitors, such as bortezomib and carfilzomib, induces severe proteotoxic stress, leading to cell cycle arrest and apoptosis. While β5 is often the primary target, the inhibition of β1 and β2 is increasingly recognized as a strategy to overcome drug resistance and enhance the efficacy of anti-cancer treatments.

Other names

PSMB6PSMB7Proteasome subunit beta type-6Proteasome subunit beta type-7Proteasome subunit beta-1Proteasome subunit beta-2Beta1 subunitBeta2 subunitDelta chain (PSMB6)Z chain (PSMB7)LMPY (PSMB6)

Reversible or irreversible inhibition of the N-terminal threonine residue within the catalytic subunits, blocking the caspase-like (β1) and trypsin-like (β2) proteolytic activities of the 20S proteasome.