Proteasome subunit beta type-9 (PSMB9) (PSMB9)

The Proteasome subunit beta type-9 (PSMB9), also known as the Immunoproteasome β1i subunit or LMP2, is a catalytic subunit of the immunoproteasome, a specialized protein degradation complex [1, 2]. Unlike the constitutive proteasome found in all cells, the immunoproteasome is predominantly expressed in immune cells or induced by inflammatory signals such as interferon-gamma [1, 15]. PSMB9 replaces the constitutive β1 subunit and provides caspase-like proteolytic activity, which is essential for generating high-affinity peptides for MHC class I antigen presentation [1, 9]. This process is vital for the immune system's ability to recognize and eliminate infected or malignant cells [1]. Overexpression of PSMB9 is linked to autoimmune diseases like systemic lupus erythematosus and rheumatoid arthritis, as well as certain cancers like multiple myeloma [1, 10]. Drugs targeting this subunit, such as zetomipzomib, are designed to selectively inhibit immunoproteasome activity to dampen pathological immune responses or induce cancer cell death while minimizing the side effects associated with broad proteasome inhibition [3, 4, 8].

Other names

LMP2Large multifunctional peptidase 220S proteasome subunit beta-1iPSMB6iRING12beta1iProteasome subunit beta 9PRAAS3Proteasome 20S subunit beta 9

Selective inhibition of the immunoproteasome β1i subunit, which disrupts the processing of antigens for MHC class I presentation and modulates pro-inflammatory cytokine production.