Redox Regulation of Forkhead Proteins Through a p66shc -Dependent Signaling Pathway
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- 29 March 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 295 (5564), 2450-2452
- https://doi.org/10.1126/science.1069004
Abstract
Genetic determinants of longevity include the forkhead-related transcription factor DAF-16 in the worm Caenorhabditis elegans and the p66shc locus in mice. We demonstrate that p66shc regulates intracellular oxidant levels in mammalian cells and that hydrogen peroxide can negatively regulate forkhead activity. In p66shc –/– cells, the activity of the mammalian forkhead homolog FKHRL1 is increased and redox-dependent forkhead inactivation is reduced. In addition, expression of FKHRL1 results in an increase in both hydrogen peroxide scavenging and oxidative stress resistance. These results demonstrate an important functional relation between three distinct elements linked to aging: forkhead proteins, p66shc , and intracellular oxidants.Keywords
This publication has 22 references indexed in Scilit:
- Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathwayCurrent Biology, 2001
- daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegansCurrent Biology, 2001
- The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegansCurrent Biology, 2001
- Oxidative Preconditioning and Apoptosis in L-cellsJournal of Biological Chemistry, 2001
- Oxidative Stress-induced Phospholipase C-γ1 Activation Enhances Cell SurvivalJournal of Biological Chemistry, 2001
- Protein Kinase SGK Mediates Survival Signals by Phosphorylating the Forkhead Transcription Factor FKHRL1 (FOXO3a)Molecular and Cellular Biology, 2001
- Longevity and heavy metal resistance indaf‐2andage‐1long‐lived mutants ofCaenorhabditis elegansThe FASEB Journal, 2001
- Akt1/PKBα Protects PC12 Cells against the Parkinsonism-Inducing Neurotoxin 1-Methyl-4-phenylpyridinium and Reduces the Levels of Oxygen-Free RadicalsMolecular and Cellular Neuroscience, 2001
- Insulin-like Growth Factor-1-induced Phosphorylation of the Forkhead Family Transcription Factor FKHRL1 Is Mediated by Akt Kinase in PC12 CellsJournal of Biological Chemistry, 2000
- Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologuesBiochemical Journal, 2000