Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress
| Autor: | Tobias B. Dansen, Karel W. A. Wirtz, Boudewijn M.T. Burgering, Johannes L. Bos, Paul J. Coffer, Ingrid Saarloos, Geert J. P. L. Kops, Paulien E. Polderman, Ting-T. Huang, René H. Medema |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cell Survival
Longevity Apoptosis Protein Serine-Threonine Kinases Biology medicine.disease_cause Models Biological Antioxidants Culture Media Serum-Free Superoxide dismutase Forkhead Transcription Factors Proto-Oncogene Proteins Tumor Cells Cultured medicine Animals Humans Insulin RNA Messenger Promoter Regions Genetic chemistry.chemical_classification Reactive oxygen species Multidisciplinary Forkhead Box Protein O1 Superoxide Dismutase JNK Mitogen-Activated Protein Kinases FOXO Family Chromatin Cell biology DNA-Binding Proteins Enzyme Activation Oxidative Stress Glucose chemistry Biochemistry Enzyme Induction Mutation FOXO4 FOXO3 biology.protein Forkhead Box Protein O3 Mitogen-Activated Protein Kinases Reactive Oxygen Species Proto-Oncogene Proteins c-akt Oxidative stress Transcription Factors |
| Zdroj: | Nature. 419:316-321 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Reactive oxygen species are required for cell proliferation but can also induce apoptosis1. In proliferating cells this paradox is solved by the activation of protein kinase B (PKB; also known as c-Akt), which protects cells from apoptosis2. By contrast, it is unknown how quiescent cells that lack PKB activity are protected against cell death induced by reactive oxygen species. Here we show that the PKB-regulated Forkhead transcription factor FOXO3a (also known as FKHR-L1) protects quiescent cells from oxidative stress by directly increasing their quantities of manganese superoxide dismutase (MnSOD) messenger RNA and protein. This increase in protection from reactive oxygen species antagonizes apoptosis caused by glucose deprivation. In quiescent cells that lack the protective mechanism of PKB-mediated signalling, an alternative mechanism is induced as a consequence of PKB inactivity. This mechanism entails the activation of Forkhead transcription factors, the transcriptional activation of MnSOD and the subsequent reduction of reactive oxygen species. Increased resistance to oxidative stress is associated with longevity. The model of Forkhead involvement in regulating longevity stems from genetic analysis in Caenorhabditis elegans3,4,5,6, and we conclude that this model also extends to mammalian systems. |
| Databáze: | OpenAIRE |
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