Proteasome subunit beta type-10 (PSMB10) (PSMB10)

Proteasome subunit beta type-10 (PSMB10), also known as β2i or MECL-1, is a catalytic component of the immunoproteasome, a specialized protein degradation complex primarily expressed in hematopoietic cells and induced by pro-inflammatory cytokines like interferon-gamma (UniProt P40306). In the immunoproteasome, PSMB10 replaces the constitutive β2 subunit (PSMB7) and provides trypsin-like activity, specifically cleaving peptide bonds after basic amino acid residues. This enzymatic activity is essential for generating peptides with the appropriate C-terminal residues for high-affinity binding to MHC class I molecules, thereby facilitating effective CD8+ T-cell-mediated immune responses (PubMed: 21115912). Dysregulation of PSMB10 has been implicated in the pathogenesis of various autoimmune and inflammatory diseases, including systemic lupus erythematosus and rheumatoid arthritis, as well as in the progression of certain hematological malignancies (PubMed: 29654258). While pan-proteasome inhibitors like bortezomib and carfilzomib target PSMB10 alongside other subunits, the development of selective immunoproteasome inhibitors aims to provide therapeutic benefit with reduced systemic toxicity compared to broad proteasome inhibition. Consequently, PSMB10 represents a significant target for modulating immune function and treating chronic inflammatory conditions.

Other names

MECL-1LMP10Macropain subunit 10Proteasome subunit beta-2iMulticatalytic endopeptidase complex subunit 10PSMB10

Inhibition of the trypsin-like proteolytic activity of the 20S immunoproteasome core, preventing the degradation of polyubiquitinated proteins and altering the repertoire of peptides presented by MHC class I molecules.