PSME3 Protein, Human (N-His)

PSME3, a subunit of the 11S REG-gamma (also known as PA28-gamma) proteasome regulator, forms a doughnut-shaped homoheptamer that associates with the proteasome. This homoheptamer plays a crucial role in activating the trypsin-like catalytic subunit of the proteasome while simultaneously inhibiting the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Notably, PSME3 facilitates the interaction between MDM2 and p53/TP53, leading to the ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53. This process limits the accumulation of p53/TP53, thereby inhibiting apoptosis following DNA damage. Additionally, PSME3 may contribute to cell cycle regulation. The stability of the PSME3 homoheptamer is crucial for its specific activation of the trypsin-like subunit and inhibition of the chymotrypsin-like and PGPH subunits of the proteasome. PSME3 interacts with various proteins, including MAP3K3, CCAR2, and PSME3IP1, the latter of which directly promotes PSME3 association with the 20S proteasome. The interaction with COIL is inhibited by PSME3IP1. This intricate network of interactions underscores the multifaceted role of PSME3 in regulating proteasome activity and influencing key cellular processes.