When NRF2 talks, who's listening?

Nobunao Wakabayashi, Stephen L. Slocum, John J. Skoko, Soona Shin, Thomas W. Kensler

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)1649-1663
Number of pages15
JournalAntioxidants and Redox Signaling
Volume13
Issue number11
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Wakabayashi, N., Slocum, S. L., Skoko, J. J., Shin, S., & Kensler, T. W. (2010). When NRF2 talks, who's listening? Antioxidants and Redox Signaling, 13(11), 1649-1663. https://doi.org/10.1089/ars.2010.3216