Proteasome 20S core particle, beta 1 and beta 2 subunits (PSMB6/PSMB7)

The Proteasome 20S core particle is the central catalytic component of the 26S proteasome complex, which is responsible for the ATP-dependent degradation of polyubiquitinated proteins within the cell (UniProt P28066). It is structured as a barrel-shaped assembly of four stacked heptameric rings, where the two inner rings contain the catalytic beta subunits. Specifically, the beta 1 (PSMB6) and beta 2 (PSMB7) subunits provide the caspase-like and trypsin-like proteolytic activities, respectively, utilizing an N-terminal threonine residue as the active site nucleophile (UniProt Q99436). In hematological malignancies such as multiple myeloma, the proteasome is often overactive to manage the high protein synthesis and turnover characteristic of malignant plasma cells (StatPearls, Proteasome Inhibitors). Therapeutic inhibition of these subunits, often in combination with the beta 5 subunit, leads to the accumulation of misfolded proteins and the stabilization of pro-apoptotic factors, ultimately triggering programmed cell death (PubMed: 15546010). While first-generation inhibitors like bortezomib primarily target the beta 5 and beta 1 subunits, newer pan-proteasome inhibitors like marizomib target all three catalytic subunits, including beta 2, to overcome drug resistance and enhance efficacy (PubMed: 21810917).

Other names

Proteasome subunit beta type-6Proteasome subunit beta type-7PSMB6PSMB720S proteasome beta 1 subunit20S proteasome beta 2 subunitCaspase-like catalytic subunitTrypsin-like catalytic subunit

Inhibition of the catalytic N-terminal threonine residues within the beta subunits of the 20S proteasome core, which prevents the degradation of regulatory and misfolded proteins, leading to proteotoxic stress and induction of apoptosis (PubMed: 17885084).