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When NRF2 Talks, Who's Listening?

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Wakabayashi, Nobunao, Slocum, Stephen L., Skoko, John J., Shin, Soona, Kensler, Thomas W.·2010·Antioxidants & Redox Signaling
DOI 10.1089/ars.2010.3216PMC PMC2966480
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Abstract

Activation of the KEAP1-NRF2 signaling pathway is an adaptive response to environmental and endogenous stresses and serves to render animals resistant to chemical carcinogenesis and other forms of toxicity, whereas disruption of the pathway exacerbates these outcomes. This pathway, which can be activated by sulfhydryl-reactive, small-molecule pharmacologic agents, regulates the inducible expression of an extended battery of cytoprotective genes, often by direct binding of the transcription factor to antioxidant response elements in the promoter regions of target genes. However, it is becoming evident that some of the protective effects may be mediated indirectly through cross talk with additional pathways affecting cell survival and other aspects of cell fate. These interactions provide a multi-tiered, integrated response to chemical stresses. This review highlights recent observations on the molecular interactions and their functional consequences between NRF2 and the arylhydrocarbon receptor (AhR), NF-κB, p53, and Notch1 signaling pathways.

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  • Lack of Nrf2 activity can exacerbate NF-κB signaling, leading to increased cytokine production; alternatively, NF-κB can modulate Nrf2 activity.

    “Lack of Nrf2 activity can exacerbate NF-κB signaling, leading to increased cytokine production; alternatively, NF-κB can modulate Nrf2 activity, having both positive and negative effects on target gene expression [152, 153].”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [153]

    The Introduction reports increased NF-κB activation in Nrf2-deficient mice after several stimuli and identifies cytokines as NF-κB targets. It does not establish that Nrf2 deficiency increased cytokine production. It also describes NF-κB regulation of NRF2 as a possibility based on a predicted promoter-binding site, rather than a demonstrated effect. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Wakabayashi, N., Slocum, S. L., Skoko, J. J., Shin, S., & Kensler, T. W.
Affiliations
Johns Hopkins University (US)
Corresponding author
Kensler, Thomas W.
ORCID
Venue
Antioxidants & Redox Signaling
Publisher
SAGE Publications
Published
2010-12
Volume
13
Issue
11
Pages
1649-1663
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
DOI
10.1089/ars.2010.3216
PMC
PMC2966480
OpenAlex
W2108995381
Cited by
595
References
11
Citations by year
2026: 15 · 2025: 22 · 2024: 22 · 2023: 23 · 2022: 42 · 2021: 45 · 2020: 53 · 2019: 42 · 2018: 42 · 2017: 45 · 2016: 43 · 2015: 49 · 2014: 35 · 2013: 53 · 2012: 31
FWCI
3.26
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (ES07141, CA94076, CA009110, T32 ES07141)
  • Samsung
  • National Cancer Institute (R01CA094076, CA 39416, R01CA039416, CA 94076, T32CA009110)
  • National Institute of General Medical Sciences (T32GM008763, T32-GM08763)
  • National Institute of Environmental Health Sciences (T32 ES07141, T32ES007141)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
Nrf2, Nrf2/Keap1 pathway, aryl hydrocarbon receptor, NF-κB, p53, Notch1 signaling, signaling crosstalk, antioxidant response element, chemical carcinogenesis, stress response, transcription factors
MeSH terms
Kelch-Like ECH-Associated Protein 1, Animals, Cell Survival, Humans, Neoplasms, Transcription Factors, Signal Transduction, Tumor Suppressor Protein p53, NF-kappa B, Receptors, Aryl Hydrocarbon, Mice, Knockout, Response Elements, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, NF-E2-Related Factor 2, Mice, Receptor, Notch1

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