When NRF2 Talks, Who's Listening?
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TLDR
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, which provide a multi-tiered, integrated response to chemical stresses.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 (A...read more
Citations
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Nrf2 signaling pathway: Pivotal roles in inflammation.
TL;DR: The members of the Keap1/Nrf2/ARE signal pathway and its downstream genes, the effects of this pathway on animal models of inflammatory diseases, and crosstalk with the NF-κB pathway are discussed.
Journal ArticleDOI
The emerging role of the Nrf2–Keap1 signaling pathway in cancer
TL;DR: The studies suggest that Nrf2 contributes to both intrinsic and acquired chemoresistance, and the challenges in the development of NRF2-based drugs for chemoprevention and chemotherapy are outlined.
Journal ArticleDOI
NRF2 and cancer: the good, the bad and the importance of context
Michael B. Sporn,Karen T. Liby +1 more
TL;DR: This Opinion article aims to rationalize conflicting perspectives by critiquing the context dependence of NRF2 functions and the experimental methods behind these conflicting data.
Journal ArticleDOI
The cytoprotective role of the Keap1–Nrf2 pathway
TL;DR: Cross-talks with other signalling pathways broadens the role of the Keap1–Nrf2 pathway in determining the fate of the cell, impacting fundamental biological processes such as proliferation, apoptosis, angiogenesis and metastasis.
Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development (dioxiny2,3,7,8-tetrachlorodibenzo-p-dioxinygene targetingyliver)
TL;DR: The Ah receptor (AHR) is a ligand-activated transcription factor that mediates a pleiotropic response to environmental contaminants such as benzo(a)pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin this paper.
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