Immunoproteasome catalytic subunit (iProteasome) (iProteasome)

The immunoproteasome is a specialized isoform of the constitutive proteasome, characterized by the replacement of catalytic subunits β1, β2, and β5 with β1i (LMP2), β2i (MECL-1), and β5i (LMP7) (Source: UniProt P28062, P28065, Q99436). It is predominantly expressed in hematopoietic cells or induced in other tissues by pro-inflammatory cytokines like interferon-gamma (Source: PMID: 23103127). The immunoproteasome optimizes the generation of peptides for MHC class I antigen presentation, thereby facilitating the detection of infected or malignant cells by CD8+ T cells (Source: PMID: 21115912). Beyond antigen processing, it regulates the production of pro-inflammatory cytokines and the differentiation of T-cell subsets, playing a critical role in the pathogenesis of autoimmune diseases and hematological malignancies (Source: PMID: 30635440). Selective inhibition of these subunits, particularly β5i and β1i, has shown therapeutic potential in treating systemic lupus erythematosus and other inflammatory conditions by modulating the production of cytokines like IL-6 and TNF-alpha (Source: Kezar Life Sciences, PMID: 27993965). Unlike non-selective proteasome inhibitors used in oncology, immunoproteasome-selective inhibitors aim to provide anti-inflammatory effects with a reduced risk of systemic toxicity and peripheral neuropathy (Source: PMID: 29438012).

Other names

LMP7 (PSMB8)LMP2 (PSMB9)MECL-1 (PSMB10)20S immunoproteasomeInducible proteasome subunitsInducible proteasome catalytic subunits

Selective or non-selective inhibition of the N-terminal threonine active sites of the β1i (LMP2), β2i (MECL-1), and β5i (LMP7) subunits, which prevents the degradation of specific protein substrates and modulates the generation of MHC class I-restricted peptides and pro-inflammatory cytokine signaling (Source: PMID: 27993965, PMID: 29438012).