PSMB8 monoclonal antibody

The 26S proteasome is a highly abundant proteolytic complex involved in the degradation of ubiquitinated substrate proteins. It consists largely of two sub-complexes, the 20S catalytic core particle (CP) and the 19S/PA700 regulatory particle (RP) that can cap either end of the CP. The CP consists of two stacked heteroheptameric β-rings (β1-7) that contain three catalytic β-subunits and are flanked on either side by two heteroheptameric α-rings (α1-7) . The RP includes a base and a lid, each having multiple subunits. The base, in part, is composed of a heterohexameric ring of ATPase subunits belonging to the AAA (ATPases Associated with diverse cellular Activities) family. The ATPase subunits function to unfold the substrate and open the gate formed by the α-subunits, thus exposing the unfolded substrate to the catalytic β-subunits. The lid consists of ubiquitin receptors and DUBs that function in recruitment of ubiquitinated substrates and modification of ubiquitin chain topology. Other modulators of proteasome activity, such as PA28/11S REG, can also bind to the end of the 20S CP and activate it. Constitutively expressed core particle subunits PSMB5, PSMB7, and PSMB6 provide chymotrypsin-like, trypsin-like, and caspase-like activities, respectively. In immune cells involved in antigen presentation, these subunits are replaced by highly homologous, induced β-subunits to form the immunoproteasome. Proteasome subunit beta type-8 (PSMB8, LMP7) is expressed as a proenzyme that is cleaved to form the mature PSMB8 (LMP7) immunoproteasome core particle subunit. Interferon-γ induces expression of PSMB8, which functionally replaces the PSMB5 core particle subunit in immunoproteasome processing of MHC class I-restricted peptide antigens. Research studies suggest that reduced PSMB8 expression or expression of the non-functional LMP7-E1 isoform may impair immunoproteasome assembly, and that PSMB8 deficiency results in reduced MHC class I molecule expression. Inhibition of PSMB8 in murine rheumatoid arthritis models attenuates disease indicators, suggesting that PSMB8 is a potential therapeutic target in the treatment of some proinflammatory autoimmune diseases. Mutations in the corresponding PSMB8 gene can cause an autoinflammatory syndrome known as CANDLE Syndrome.

LMP7; PSMB5i; RING10; Y2; Proteasome subunit beta type-8; Low molecular mass protein 7; Macropain subunit C13; Multicatalytic endopeptidase complex subunit C13; Proteasome component C13; Proteasome subunit beta-5i; Really interesting new gene 10 protein