1. The ATM protein kinase and cellular redox signaling: beyond the DNA damage response
- Author
-
Tanya T. Paull and Scott Ditch
- Subjects
Tumor Suppressor Proteins ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,Biology ,Glutathione ,Biochemistry ,Article ,MAP2K7 ,Cell biology ,DNA-Binding Proteins ,Oxidative Stress ,Animals ,Humans ,ASK1 ,CHEK1 ,c-Raf ,Protein kinase A ,Oxidation-Reduction ,Molecular Biology ,Ataxia telangiectasia and Rad3 related ,Protein kinase C ,DNA-PKcs ,DNA Damage ,Signal Transduction - Abstract
The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its role in the DNA damage response, but recent findings suggest that it also functions as a redox sensor that controls the levels of reactive oxygen species in human cells. Here, we review the evidence supporting the conclusion that ATM can be directly activated by oxidation, as well as various observations from ATM-deficient patients and mouse models that point toward the importance of ATM in oxidative stress responses. We also discuss the roles of this kinase in regulating mitochondrial function and metabolic control through its action on tumor suppressor p53, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 (HIF-1), and how the regulation of these enzymes may be affected in ATM-deficient patients and in cancer cells.
- Published
- 2012
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