title: ATM is a redox sensor linking genome stability and carbon metabolism.
abstract: In response to oxidative stress, central carbohydrate metabolism is reconfigured so that the metabolic flux reroutes from glycolysis into the pentose phosphate pathway (PPP), which allows cells to mount an effective response to this cellular stress. The kinase ataxia telangiectasia mutated (ATM) regulates this metabolic shift in mammalian cells. Upon ATM activation, the rate-limiting PPP enzyme glucose 6-phosphate dehydrogenase (G6PDH) formed a complex with heat shock protein 27 that increased G6PDH activity, augmented NADP(+) to NADPH reduction, and stimulated nucleotide synthesis. As such, ATM antagonizes the tumor suppressor p53, which is a direct inhibitor of G6PDH and the PPP. In addition to its role in DNA repair and the cell cycle, ATM is thus a component of the eukaryotic redox-sensing system. By linking genome stability, the cell cycle, and carbon catabolism, ATM emerges as a central regulator of cellular metabolism with implications for cancer.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Krüger
authors.forename: Markus
authors.initials: M
authors.lastname: Ralser
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002244:Carbon / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042822:Genomic Instability / Q000502:physiology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D002244:Carbon; D005954:Glucosephosphate Dehydrogenase; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases