| PSMC2, also termed 26S proteasome regulatory subunit 7 or Rpt1, is an AAA‑ATPase of the 19S regulatory particle base that forms part of the heterohexameric ATPase ring responsible for substrate engagement, unfolding, and translocation into the 20S proteolytic core of the 26S proteasome. The protein belongs to the AAA family of P‑loop NTPases and contributes ATP‑binding and hydrolysis motifs that power conformational changes in the base, and together with the other five ATPase subunits and adjacent non‑ATPase scaffolds, it helps form the substrate‑processing channel that recognizes polyubiquitin‑tagged proteins, unfolds them, and threads them into the catalytic chamber for peptide bond cleavage. Within the 19S base, PSMC2 associates with partners including other ATPase subunits such as PSMC1 and PSMC4 and non‑ATPase subunits such as PSMD5, and it supports assembly and stability of the regulatory particle and its docking onto the 20S core, ensuring efficient coupling between ubiquitin recognition, deubiquitination, unfolding, and proteolysis. PSMC2 expression is detected in multiple tissues where constitutive proteasome activity is required to remove misfolded or damaged proteins, terminate signaling by timely degradation of regulatory factors, and generate peptides for MHC class I antigen presentation, linking this ATPase to cell cycle control, apoptosis, DNA damage responses, and immune surveillance as part of the core ubiquitin–proteasome system. PSMC2 displays context‑dependent regulatory functions in tumor biology: in breast cancer, PSMC2 overexpression promotes proliferation, colony formation, migration, and tumor growth, and mechanistic analyses show that PSMC2 interacts with urokinase‑type plasminogen activator (PLAU), enhances its protein abundance, and thereby supports plasminogen activation, matrix remodeling, and downstream signaling that favor tumor progression. PSMC2 is upregulated and associates with advanced clinicopathologic features; functional work links PSMC2 to activation of the mTOR pathway by increasing ribosomal protein S15A through regulation of hsa‑let‑7c‑3p, indicating that this ATPase connects proteasome function to translational control and growth signaling in this context. |
