Proteasome subunit beta type-5 (PSMB5) (PSMB5)

Proteasome subunit beta type-5 (PSMB5) is a critical catalytic component of the 20S proteasome core, a multicatalytic proteinase complex responsible for the non-lysosomal degradation of most intracellular proteins. It provides the essential chymotrypsin-like activity of the proteasome, cleaving peptide bonds following large hydrophobic residues. This activity is vital for maintaining cellular protein homeostasis, regulating the cell cycle by degrading cyclins, and facilitating the immune response through the generation of MHC class I-presented peptides. PSMB5 is a validated therapeutic target in hematological malignancies like multiple myeloma and mantle cell lymphoma, where its inhibition by drugs such as bortezomib and carfilzomib triggers proteotoxic stress and apoptosis. Clinical challenges include the emergence of drug resistance, frequently driven by point mutations in the PSMB5 binding pocket or its transcriptional upregulation.

Other names

20S proteasome subunit beta-5Proteasome subunit XMB1LMPXProteasome catalytic subunit 3Macropain epsilon chainMulticatalytic endopeptidase complex epsilon chain

Selective inhibition of the chymotrypsin-like proteolytic activity of the 20S proteasome beta-5 subunit, resulting in the accumulation of polyubiquitinated proteins, induction of the unfolded protein response, and activation of apoptotic pathways.