The glycolytic enzyme PGK1 phosphorylates MORC2 to Confer radioresistance in pancreatic ductal adenocarcinoma.

ABSTRACT: Most pancreatic cancer patients exhibit inherent resistance to radiation therapy, and the molecular mechanisms remain poorly understood. Here, we demonstrate that phosphoglycerate kinase 1 (PGK1), a key ATP-producing glycolytic enzyme, plays a critical role in pancreatic ductal adenocarcinoma (PDAC) radioresistance. In response to ionizing radiation (IR), casein kinase 2 (CK2) is activated and phosphorylates PGK1 at S256. Phosphorylated PGK1 interacts with microrchidia CW-type zinc finger 2 (MORC2). Importantly, PGK1 functions as a protein kinase and phosphorylates MORC2 at S711, thereby enhancing the DNA-dependent ATPase activity of MORC2 to facilitate chromatin remodeling and DNA repair. Disruption of CK2-mediated PGK1 phosphorylation or PGK1-dependent MORC2 phosphorylation sensitizes PD

SUBMITTER: Tong Y 

PROVIDER: S-EPMC12603276 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature