19S proteasome AAA-ATPase subunits (PSMC1-PSMC6) (PSMC)

The AAA+ ATPase subunits of the 19S regulatory proteasome particle, comprising PSMC1 through PSMC6, form a hexameric ring that serves as the mechanical engine of the 26S proteasome (Source: UniProt). These subunits utilize ATP hydrolysis to recognize, unfold, and translocate polyubiquitinated protein substrates into the 20S core for degradation (Source: Annual Review of Biochemistry, PMID: 30089918). This process is essential for maintaining cellular proteostasis and regulating key processes such as the cell cycle and DNA repair (Source: PNAS, PMID: 27851968). In cancers like multiple myeloma, the proteasome is often upregulated, making these subunits attractive therapeutic targets (Source: Frontiers in Oncology, PMID: 32983998). While current clinical inhibitors like bortezomib target the 20S core, the 19S ATPases are emerging as targets for novel small molecules designed to overcome drug resistance (Source: Journal of Medicinal Chemistry, PMID: 29161035). Inhibition of these ATPases leads to the accumulation of misfolded proteins and triggers apoptosis via the unfolded protein response (Source: Cell Death & Disease, PMID: 23154387).

Other names

Rpt subunitsRegulatory particle triple-A ATPase subunits26S proteasome ATPase subunitsPSMC1-PSMC619S ATPase ringProteasome 26S subunit, ATPase

Inhibition of ATP-dependent protein unfolding and translocation into the 20S proteasome core, leading to proteotoxic stress and apoptosis.