Proteasome 26S subunit ATPase 3 (PSMC3)

Proteasome 26S subunit ATPase 3 (PSMC3) is a key enzyme within the AAA+ ATPase family and forms part of the base of the 19S regulatory particle of the 26S proteasome, which governs ATP-dependent degradation of ubiquitinated proteins in eukaryotic cells[1][2][3]. By binding and hydrolyzing ATP, PSMC3 drives the unfolding and translocation of substrate proteins into the proteolytic core, playing an essential role in protein homeostasis, cell cycle progression, response to cellular stress, and antigen processing[1][3][4]. Variants or dysfunctions in PSMC3 can lead to the accumulation of misfolded proteins, proteotoxic stress, and diseases such as neurodevelopmental disorders, cataract, deafness, and cancers[2]. While most approved drugs targeting the proteasome act on the core complex (not PSMC3 specifically), inhibition of proteasome function disrupts the pathway in which PSMC3 participates and can have profound therapeutic and safety implications[1][3].

Other names

26S proteasome regulatory subunit 6ATBP1TBP-1RPT5Proteasome 26S subunit ATPase 3Proteasome subunit p50Tat-binding protein 1DCIDPhuman immunodeficiency virus tat transactivator binding protein-1proteasome (prosome, macropain) 26S subunit, ATPase, 3testicular secretory protein Li 42

Inhibition of proteasome activity (most clinical drugs target the 20S core but disrupt overall proteasome function, including subunits like PSMC3) Proteasome inhibition leads to accumulation of misfolded/damaged proteins and apoptosis, especially in rapidly dividing cells