Proteasome subunit beta type-5 (PSMB5) and Proteasome subunit beta type-8 (PSMB8) (PSMB5 and PSMB8)

The proteasome subunit beta type-5 (PSMB5) and the proteasome subunit beta type-8 (PSMB8, also known as LMP7) are the primary catalytic components responsible for the chymotrypsin-like activity within the ubiquitin-proteasome system (UniProt P28074, P28062). PSMB5 is a constitutive subunit found in all cells, essential for degrading misfolded or damaged proteins to maintain cellular homeostasis (PubMed PMID: 21685913). PSMB8 is the inducible counterpart found in the immunoproteasome, which is upregulated in response to inflammatory signals and plays a specialized role in generating peptides for MHC class I antigen presentation (NCBI Gene ID: 5696). Because cancer cells, particularly multiple myeloma cells, are highly dependent on proteasome activity to manage high protein synthesis rates, these subunits are major therapeutic targets (FDA: Velcade Label). Drugs like bortezomib and carfilzomib inhibit both subunits to induce proteotoxic stress and apoptosis in malignant cells (PubMed PMID: 12574108). Additionally, selective inhibition of the LMP7 subunit is being investigated as a way to treat autoimmune diseases by modulating immune cell function without the broad toxicity of constitutive proteasome inhibition (Kezar Life Sciences: Zetomipzomib).

Other names

PSMB5PSMB8LMP7Proteasome subunit beta type-5Proteasome subunit beta type-8Beta5Beta5iRING10Macropain subunit C13Multicatalytic endopeptidase complex subunit C13Low molecular mass protein 7

Inhibition of the chymotrypsin-like proteolytic activity of the 20S proteasome and immunoproteasome, leading to protein homeostasis disruption and apoptosis (StatPearls: Proteasome Inhibitors).