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The AhR–Nrf2 Pathway in Keratinocytes: On the Road to Chemoprevention?
Thomas Haarmann-Stemmann, Josef Abel, Ellen Fritsche, Jean Krutmann Journal of Investigative Dermatology Volume 132, Issue 1, Pages 7-9 (January 2012) DOI: /jid Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 1 Activation of the AhR–Nrf2 pathway by the fungicide ketoconazole (KCZ). KCZ binds to the cytosolic AhR, resulting in its nuclear translocation and subsequent dimerization with ARNT. The AhR–ARNT complex binds to xenobiotic-responsive elements (XREs) in the promoters of target genes (e.g., CYP1A1) and stimulates transcription. Simultaneously, activation of AhR initiates dissociation of the Nrf2–kelch-like ECH-associated protein 1 (Keap1) complex via an unknown molecular mechanism, but one that probably includes activation of protein kinases. Phosphorylated Nrf2 translocates in the nucleus and binds to small Maf proteins. This transcriptionally active complex recognizes antioxidant-responsive elements (AREs) in promoter sequences and induces expression of target genes, e.g., NAD(P)H:quinone oxidoreductase 1 (NQO1). Journal of Investigative Dermatology , 7-9DOI: ( /jid ) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions
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Journal of Investigative Dermatology 2012 132, 7-9DOI: (10. 1038/jid
Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions
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