Cited by 818Genetics, Aging, and Longevity in Model OrganismsRedox biology and oxidative stressFOXO transcription factor regulation

Redox Regulation of Forkhead Proteins Through a p66shc -Dependent Signaling Pathway

Nemoto, Shino, Finkel, Toren·2002·Science

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.

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Crossref · 10.1126/science.1069004

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Authors
Nemoto, S., & Finkel, T.
Affiliations
National Institutes of Health (US)
Corresponding author
Finkel, Toren
Venue
Science
Published
2002-03-29
Volume
295
Issue
5564
Pages
2450-2452
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2023973783
Cited by
818
References
23
Citations by year
2026: 5 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 13 · 2021: 16 · 2020: 33 · 2019: 23 · 2018: 24 · 2017: 41 · 2016: 25 · 2015: 34 · 2014: 46 · 2013: 44 · 2012: 42
FWCI
12.47
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Keywords
p66Shc, forkhead transcription factor, FKHRL1, DAF-16, redox regulation, hydrogen peroxide, oxidative stress resistance, aging, longevity, Caenorhabditis elegans, hydrogen peroxide scavenging
MeSH terms
Forkhead Box Protein O1, Forkhead Box Protein O3, Src Homology 2 Domain-Containing, Transforming Protein 1, Acetylcysteine, Animals, Azoles, Blood, Cells, Cultured, Culture Media, DNA-Binding Proteins, Humans, Hydrogen Peroxide, Mutation, Nerve Tissue Proteins, Oxidation-Reduction, Phosphorylation, Proteins, Proto-Oncogene Proteins, Transcription Factors, Transfection, Signal Transduction, Free Radical Scavengers, Organoselenium Compounds, PC12 Cells, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Oxidative Stress, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Mice, Rats, Forkhead Transcription Factors, Isoindoles, Shc Signaling Adaptor Proteins

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