Proteasome subunit beta type-7 (PSMB7) (PSMB7)

The 20S proteasome beta 2 subunit, encoded by the PSMB7 gene, is one of the three catalytic subunits located within the 20S core particle of the 26S proteasome [3, 8]. It is specifically responsible for the "trypsin-like" proteolytic activity, which cleaves peptide bonds after basic amino acid residues [8, 14]. This subunit is essential for the degradation of misfolded, damaged, and regulatory proteins, thereby maintaining cellular proteostasis and regulating critical pathways such as the cell cycle, apoptosis, and NF-kappaB signaling [1, 6, 12]. In many cancers, including multiple myeloma and colorectal adenocarcinoma, PSMB7 is overexpressed and serves as a prognostic biomarker for poor survival and drug resistance [1, 15, 28]. While first-generation proteasome inhibitors like bortezomib primarily target the beta 5 subunit, they also interact with beta 2 at therapeutic concentrations [1, 13, 33]. Experimental selective beta 2 inhibitors, such as LU-102, have shown promise in sensitizing resistant cancer cells to existing therapies by inducing severe proteotoxic stress and the unfolded protein response [20, 21, 34]. Consequently, the beta 2 subunit represents a significant co-target in the development of next-generation proteasome-modulating therapies [22, 23].

Other names

20S proteasome subunit beta-2Proteasome subunit beta-2ZMacropain chain ZMulticatalytic endopeptidase complex chain ZProteasome subunit ZTrypsin-like proteasome subunit

Inhibition of the trypsin-like proteolytic activity of the 20S proteasome [8, 14, 29]