PSMB6 (E1K9O) Rabbit Monoclonal Antibody #13267

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 (β_1-7) that contain three catalytic β-subunits and are flanked on either side by two heteroheptameric α-rings (α_1-7). 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 (1,2). Other modulators of proteasome activity, such as PA28/11S REG, can also bind to the end of the 20S CP and activate it (1,2).
The core particle exhibits three distinct enzymatic activities, each catalyzed by a separate protein subunit. The constitutively expressed PSMB5, PSMB7, and PSMB6 subunits provide chymotrypsin-like, trypsin-like, and caspase-like activities, respectively. These catalytic subunits belong to the amino-terminal nucleophile (Ntn) hydrolase family and are characterized by a single-residue active site. The catalytic β-subunits are synthesized with amino-terminal propeptides, which are removed at the final step of proteasome biogenesis to expose the catalytic threonine residues (3). In immune cells involved in antigen presentation, the constitutively expressed PSMB6, PSMB7, and PSMB5 subunits are replaced by three highly homologous, induced β-subunits to form the immunoproteasome (4,5). PSMB6 is downregulated at the protein level by IFN-γ and replaced by PSMB9 in order to remodel the proteolytic specificity of the proteasome for more appropriate immunological processing of endogenous antigens (6-8).