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Forkhead Box O as a Sensor, Mediator, and Regulator of Redox Signaling
Abstract
The forkhead box O (FOXO) family of transcription factors regulates a variety of cellular programs, including cell cycle arrest, reactive oxygen species (ROS) scavenging, and apoptosis, and are of key importance in the decision over cell fate. In animal model systems it has been shown that FOXO is involved in the regulation of long lifespan. FOXO activity is tightly controlled by the insulin signaling pathway and by a multitude of ROS-induced posttranslational modifications. In the cell, ROS levels can be sensed by virtue of stimulatory and inhibitory oxidative modification of cysteine residues within proteins that control various signaling cascades. Recently, it was shown that cysteines in FOXO can also act as sensors of the local redox state. In this review we have outlined the cysteine-dependent redox switches that regulate both the insulin and ROS signaling pathways upstream of FOXO. Further, we describe how FOXO controls ROS levels by transcriptional regulation of a multilayered antioxidant system. Finally, we will discuss how cysteine-based redox signaling to FOXO could play a role in fine-tuning the optimal cellular response to ROS to control organismal lifespan. Antioxid. Redox Signal. 14, 1093–1106.
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“Various kinases and transcription factors, involved in neuropeptide regulation, have been reported to be modulated by redox signaling ([33](#B33), [91](#B91)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [33]
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Metadata
- Authors
- de Keizer, P. L. J., Burgering, B. M. T., & Dansen, T. B.
- Affiliations
- University Medical Center Utrecht
- University Medical Center Utrecht (NL)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2011-03
- Volume
- 14
- Issue
- 6
- Pages
- 1093-1106
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W1986717393
- Cited by
- 131
- References
- 80
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 3 · 2019: 7 · 2018: 13 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 14 · 2013: 15 · 2012: 13
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- FOXO transcription factors, forkhead box O, redox signaling, reactive oxygen species, insulin signaling, lifespan regulation, oxidative stress, apoptosis, cell cycle arrest
- MeSH terms
- Animals, Cysteine, Humans, Models, Biological, Oxidation-Reduction, Signal Transduction, Reactive Oxygen Species, Forkhead Transcription Factors
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