Proteasome subunit beta (PSMB)

Proteasome beta subunits are the catalytic components of the 20S core particle within the 26S proteasome complex, which is essential for the ATP-dependent degradation of ubiquitinated proteins (UniProt: P28074). In the constitutive proteasome, seven distinct beta subunits (PSMB1-PSMB7) form the inner rings of the barrel-shaped 20S core, with PSMB5, PSMB2, and PSMB1 exhibiting chymotrypsin-like, trypsin-like, and caspase-like proteolytic activities, respectively (PubMed: 15546512). These subunits play a pivotal role in maintaining cellular proteostasis by removing misfolded or damaged proteins and regulating the levels of regulatory proteins involved in the cell cycle and apoptosis. In hematologic malignancies, particularly multiple myeloma, cancer cells become highly dependent on proteasome activity to manage the high volume of monoclonal protein production and avoid proteotoxic stress (StatPearls: NBK545185). Drugs targeting these subunits, such as bortezomib and carfilzomib, induce apoptosis by causing the accumulation of misfolded proteins and triggering the unfolded protein response (UPR). Beyond oncology, these subunits are also investigated as therapeutic targets for inflammatory and autoimmune disorders due to their role in cytokine signaling and MHC class I antigen presentation (PubMed: 21670737).

Other names

20S proteasome beta subunitProteasome catalytic subunitMulticatalytic endopeptidase complex beta subunitPSMB subunit

Inhibition of the N-terminal threonine active sites within the beta subunits of the 20S proteasome core, primarily targeting chymotrypsin-like activity to block the degradation of polyubiquitinated proteins (StatPearls: NBK545185).