The cunning little vixen: Foxo and the cycle of life and death
Open accessAbstract
A screen for increased longevity in Caenorhabditis elegans has identified a transcription factor that programs cells for resistance to oxidative stress, DNA repair and cell cycle control. The mammalian orthologs of this factor are referred to as 'Foxo' for 'Forkhead box', with the second 'o' in the name denoting a subfamily of four members related by sequence. This family of factors is regulated by growth factors, oxidative stress or nutrient deprivation. Thus, it might readily control the inflammatory conflagration associated with infection-driven lymphocyte proliferation. Surprisingly, the first insights into Foxo-mediated immune regulation have instead revealed direct control of highly specialized genes of the adaptive immune system.
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Akt phosphorylates FOXO transcription factors on three conserved residues, resulting in cytosolic sequestration through interaction with 14-3-3 adaptor proteins.
“Akt phosphorylates forkhead box O (FOXO) transcription factors on three conserved residues, resulting in cytosolic sequestration through interaction with 14-3-3 adaptor proteins 34.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [34]
FOXO-mediated transcription is activated upon cellular stress, including oxidative stress, via phosphorylation events mediated by JNK, MST1, or AMPK.
“FOXO-mediated transcription is activated upon cellular stress, including oxidative stress, via phosphorylation events mediated by JNK (c-Jun N-terminal kinase), MST1 (mammalian Sterile20-like 1), or AMPK 34.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [34]
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References 98 · Cited by 157
- Authors
- Hedrick, S. M.
- Venue
- Nature Immunology
- Published
- 2009-08-23
- Volume
- 10
- Issue
- 10
- Pages
- 1057-1063
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2856448
- OpenAlex
- W2030410762
- Cited by
- 157
- References
- 98
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 3 · 2015: 12 · 2014: 11 · 2013: 11 · 2012: 24
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI073885)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- FOXO, forkhead transcription factor, oxidative stress resistance, DNA repair, cell cycle regulation, adaptive immunity, lymphocyte proliferation, immune regulation, growth factors, nutrient deprivation
- MeSH terms
- Animals, Gene Expression Regulation, Homeostasis, Humans, Immunity, Forkhead Transcription Factors
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