PSMG1/PAC1 Antibody #13378

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).
Proteasome assembly chaperone 1 (PSMG1, PAC1) is an evolutionarily conserved, ubiquitously expressed chaperone protein that promotes proper biogenesis of the α-ring of the 20S CP of the eukaryotic proteasome (3,4). PSMG1 (PAC1) functions in a heterodimeric complex with PSMG2 (PAC2) and was originally identified as a proteasome subunit binding partner (4). Intact PSMG1-PSMG2 heterodimers both promote heteroheptameric α-ring assembly and/or stability and prevent accumulation of non-productive α-ring dimers (4). Research studies targeting the disruption of the murine Psmg1 locus have substantiated the importance of proteasome chaperones in contributing to normal proteasome maturation and cellular homeostasis by demonstrating that loss of Psmg1/Pac1 function leads to embryonic lethality (5).