Proteasome subunit beta type 10 (PSMB10)

Proteasome subunit beta type 10 (PSMB10), also known as MECL-1 or LMP10, is a catalytic subunit of the immunoproteasome, a specialized protein degradation complex primarily expressed in hematopoietic cells and induced by pro-inflammatory cytokines like interferon-gamma [1, 2]. It replaces the constitutive beta-2 subunit and provides the complex with trypsin-like proteolytic activity, which is essential for processing antigens into peptides suitable for MHC class I presentation [1, 4]. By modulating the repertoire of presented peptides, PSMB10 plays a pivotal role in the adaptive immune response and the regulation of T-cell activation [5]. Dysregulation or overactivity of PSMB10 is associated with various autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis, as well as certain hematological malignancies [3, 5]. Consequently, PSMB10 is a significant therapeutic target; selective inhibitors like zetomipzomib (KZR-616) are designed to block its activity to reduce the production of pro-inflammatory cytokines and alleviate autoimmune symptoms [3, 4]. While broad-spectrum proteasome inhibitors like bortezomib also target PSMB10, selective immunoproteasome inhibition offers a strategy to achieve therapeutic efficacy with reduced systemic toxicity compared to constitutive proteasome inhibition [4]. Sources: [1] UniProt (P40306); [2] NCBI Gene (5699); [3] Kezar Life Sciences (Zetomipzomib); [4] PMID: 28847450; [5] PMID: 31515258.

Other names

LMP10MECL1Proteasome subunit beta-2iMacropain subunit MECL1Multicatalytic endopeptidase complex subunit MECL1Proteasome (prosome, macropain) subunit, beta type, 10

Inhibition of the trypsin-like catalytic activity of the immunoproteasome to modulate immune signaling and protein homeostasis.