Proteasome 26S subunit ATPase 2 (PSMC2)

Proteasome 26S subunit ATPase 2 (PSMC2) is an essential AAA+ ATPase enzyme component of the 19S regulatory particle in the 26S proteasome complex, which is the principal eukaryotic protease for ATP-dependent degradation of ubiquitinated proteins. PSMC2, also known as Rpt1, is one of six homologous ATPase subunits that form a heterohexameric ring critical for substrate recognition, unfolding, and translocation into the 20S proteolytic core. The 26S proteasome maintains protein homeostasis by removing damaged, misfolded, or regulatory proteins and plays key roles in cell cycle regulation, apoptosis, antigen processing, and DNA repair. Aberrant expression of PSMC2 has been strongly linked to oncogenesis, with overexpression promoting tumor progression, while its inhibition results in cell cycle arrest and apoptosis, making it an important anti-cancer target. The broader proteasome system is the pharmacological target of several approved anti-cancer drugs (e.g., bortezomib), though these typically target the entire 26S complex rather than PSMC2 alone.

Other names

26S proteasome regulatory subunit 7RPT1MSS1S7Nbla10058Proteasome 26S subunit, ATPase, 226S proteasome AAA-ATPase subunit RPT1mammalian suppressor of sgv-1 of yeasttestis secretory sperm-binding protein Li 197a

Inhibition of the proteasome results in accumulation of ubiquitinated proteins, leading to cell cycle arrest, induction of apoptosis, and disruption of multiple signaling pathways; broadly relevant to anti-cancer mechanisms