20S proteasome subunit beta-1 and beta-2 (PSMB6/PSMB7)

The 20S proteasome is the catalytic core of the 26S proteasome complex, a multi-protein assembly responsible for the degradation of polyubiquitinated proteins in the eukaryotic cytosol and nucleus [1]. It is composed of four stacked rings, where the two inner rings contain the catalytic subunits beta-1 (PSMB6), beta-2 (PSMB7), and beta-5 (PSMB5) [2]. The beta-1 subunit possesses caspase-like activity, cleaving peptide bonds after acidic residues, while the beta-2 subunit possesses trypsin-like activity, cleaving after basic residues [3]. Although most clinical proteasome inhibitors primarily target the chymotrypsin-like activity of the beta-5 subunit, the beta-1 and beta-2 subunits are critical for the complete degradation of diverse protein substrates and are targeted to enhance therapeutic efficacy [4][5]. Inhibition of these subunits leads to the accumulation of misfolded proteins, triggering the unfolded protein response and ultimately resulting in programmed cell death, particularly in malignant cells like those in multiple myeloma [6].

Other names

PSMB6PSMB7Proteasome subunit beta type-6Proteasome subunit beta type-7Caspase-like subunitTrypsin-like subunitMacropain subunit deltaMacropain subunit Z

Inhibition of the N-terminal threonine residues of the PSMB6 (beta-1) and PSMB7 (beta-2) subunits within the 20S proteasome core, which blocks caspase-like and trypsin-like proteolytic activities, leading to the accumulation of polyubiquitinated proteins and induction of apoptosis [3][4].