Proteasome 20S subunit beta type 5 (PSMB5) (PSMB5)

Proteasome 20S subunit beta type 5 (PSMB5) is a critical catalytic component of the 20S core proteasome, a multi-subunit enzyme complex responsible for the degradation of intracellular proteins. PSMB5 specifically provides the chymotrypsin-like activity, which is the rate-limiting step in protein degradation via the ubiquitin-proteasome pathway (UniProt P28074). By regulating the turnover of proteins involved in cell cycle progression and apoptosis, PSMB5 maintains cellular proteostasis and is essential for cell survival. In many cancers, especially multiple myeloma, cells become highly dependent on proteasome activity to manage the high load of misfolded proteins, making PSMB5 a validated therapeutic target (PubMed: 27510513). Drugs like bortezomib and carfilzomib bind to the active site of PSMB5, inhibiting its function and triggering programmed cell death in malignant cells. However, clinical challenges include the development of resistance through point mutations in the PSMB5 binding pocket and the management of systemic toxicities like peripheral neuropathy (PubMed: 21490304).

Other names

PSMB5Proteasome subunit beta type-5Macropain subunit epsilonMulticatalytic endopeptidase complex subunit epsilonProteasome subunit MB1

Inhibition of the chymotrypsin-like proteolytic activity of the 20S proteasome core, leading to the accumulation of polyubiquitinated proteins, induction of proteotoxic stress, and activation of apoptotic pathways.