26S proteasome β1 and β2 catalytic subunits (PSMB6 and PSMB7)

The 26S proteasome β1 and β2 catalytic subunits, encoded by the PSMB6 and PSMB7 genes respectively, are essential components of the 20S core particle within the 26S proteasome complex [1.1.1, 1.4.1]. These subunits are responsible for the caspase-like and trypsin-like proteolytic activities, respectively, which are necessary for the degradation of polyubiquitinated proteins [1.3.2, 1.4.3]. This degradation process is vital for maintaining cellular protein quality control, regulating the cell cycle, and generating peptides for MHC class I antigen presentation [1.1.2, 1.4.5]. In oncology, particularly in multiple myeloma and mantle cell lymphoma, these subunits are critical therapeutic targets; drugs like bortezomib and marizomib inhibit their activity to induce proteotoxic stress and apoptosis in cancer cells [1.3.1, 1.4.2]. Furthermore, mutations or altered expression of these subunits are linked to proteasome-associated autoinflammatory syndromes (PRAAS) and the development of resistance to proteasome inhibitors [1.1.1, 1.2.1].

Other names

Proteasome subunit beta type-6Proteasome subunit beta type-720S proteasome subunit beta-120S proteasome subunit beta-2PSMB6PSMB7DeltaZLMPYY

Inhibition of the N-terminal threonine catalytic sites of the β1 (caspase-like) and β2 (trypsin-like) subunits of the 20S proteasome core, leading to the accumulation of misfolded proteins, induction of the unfolded protein response (UPR), and subsequent apoptosis [1.3.1, 1.3.3].