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

The Proteasome subunit beta type-6 (PSMB6) and Proteasome subunit beta type-7 (PSMB7) are essential catalytic components of the 20S core particle within the 26S proteasome complex (UniProt P28072, P28074). PSMB6 is responsible for caspase-like (peptidyl-glutamyl peptide-hydrolyzing) activity, while PSMB7 provides trypsin-like activity, both of which are critical for the degradation of polyubiquitinated proteins (PubMed: 21745586). These subunits play a vital role in maintaining cellular homeostasis by regulating the levels of proteins involved in the cell cycle, DNA repair, and apoptosis (PubMed: 16169928). In various malignancies, particularly multiple myeloma and mantle cell lymphoma, the proteasome is often overexpressed or hyperactive to manage the high burden of misfolded proteins, making it a key therapeutic target (PubMed: 29156660). While many proteasome inhibitors primarily target the beta 5 subunit, drugs like marizomib and bortezomib also inhibit the beta 1 and beta 2 subunits to varying degrees to overcome drug resistance and enhance anti-tumor activity (PubMed: 26383821). Inhibition of these subunits leads to the accumulation of pro-apoptotic factors and the induction of the unfolded protein response, ultimately resulting in cancer cell death (PubMed: 19103607).

Other names

Proteasome subunit beta type-1Proteasome subunit beta type-220S proteasome subunit beta 120S proteasome subunit beta 2Caspase-like subunitTrypsin-like subunitPSMB6PSMB7

Proteasome inhibition