Proteasome activator complex subunit 4 (PA200)

Proteasome activator complex subunit 4 (PA200) is a large, evolutionarily conserved, nuclear-localized monomeric protein (approximately 200 kDa) encoded by the PSME4 gene[5]. PA200 binds to the 20S proteasome and can form hybrid complexes with 19S and 20S subunits, modulating proteasome function[2][5]. Unlike the canonical 19S regulator, which targets ubiquitylated proteins for ATP-dependent degradation, PA200 activates the proteasome in an ATP- and ubiquitin-independent manner, mainly stimulating the hydrolysis of small peptides and the degradation of acetylated histones[1][3][4][5]. PA200 is thought to participate in the cellular response to DNA damage, particularly by promoting protein turnover and maintaining genomic stability following genotoxic stress[2]. Its precise role in DNA repair remains debated, but PA200-deficient cells exhibit increased genomic instability and hypersensitivity to DNA-damaging agents[1][2]. Both its protein and gene name abbreviations—PA200 and PSME4—are commonly used in the scientific literature. Caveats and limitations: There are no approved therapeutic drugs directly targeting PA200, and its utility as a biomarker or direct drug target is still under investigation[3][5]. Its role in disease, particularly cancer and genomic instability, is still primarily mechanistic and not yet leveraged in clinical settings[2][5].

Other names

PA200PSME4Proteasome activator subunit 4Blm10 (S. cerevisiae ortholog)