CDH1 Orchestrates Anabolic Events to Promote Cell Cycle Initiation.

ABSTRACT: Cell proliferation requires anabolic supports. How the cell cycle integrates anabolism remains poorly understood. Herein, it is identified that G1-phase regulator cell division cycle 20-like protein 1 (CDH1) coordinates anabolic events to ensure cell cycle initiation. CDH1 degrades Von Hippel-Lindau (VHL), concomitantly activates hypoxia-inducible factor 1α (HIF1α), which enhances angiogenesis and glucose metabolism, and activates mitochondrial lactyltransferase alanyl tRNA synthetase (AARS2), which lactylates and inactivates pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), thereby conserving anabolites. Among the CDH1-accumulated anabolites, ribose-5-phosphate (R5P) binds to transketolase-like-1 (TKTL1) to bridge CDH1 to cyclin-dependent kinase 2 (CDK2) and Skp1-Cullin-F-box and β-trans

SUBMITTER: Mao YZ 

PROVIDER: S-EPMC12713023 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature