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Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

Author

Listed:
  • Evanna L. Mills

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
    Dana-Farber Cancer Institute, Harvard Medical School
    Harvard Medical School
    GlaxoSmithKline, Gunnelswood Road)

  • Dylan G. Ryan

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Hiran A. Prag

    (MRC Mitochondrial Biology Unit, University of Cambridge,)

  • Dina Dikovskaya

    (Jacqui Wood Cancer Centre, School of Medicine, University of Dundee)

  • Deepthi Menon

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Zbigniew Zaslona

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Mark P. Jedrychowski

    (Dana-Farber Cancer Institute, Harvard Medical School
    Harvard Medical School)

  • Ana S. H. Costa

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre)

  • Maureen Higgins

    (Jacqui Wood Cancer Centre, School of Medicine, University of Dundee)

  • Emily Hams

    (School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • John Szpyt

    (Harvard Medical School)

  • Marah C. Runtsch

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Martin S. King

    (MRC Mitochondrial Biology Unit, University of Cambridge,)

  • Joanna F. McGouran

    (School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Roman Fischer

    (Target Discovery Institute, University of Oxford)

  • Benedikt M. Kessler

    (Target Discovery Institute, University of Oxford)

  • Anne F. McGettrick

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Mark M. Hughes

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Richard G. Carroll

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
    GlaxoSmithKline, Gunnelswood Road)

  • Lee M. Booty

    (GlaxoSmithKline, Gunnelswood Road
    MRC Mitochondrial Biology Unit, University of Cambridge,)

  • Elena V. Knatko

    (Jacqui Wood Cancer Centre, School of Medicine, University of Dundee)

  • Paul J. Meakin

    (School of Medicine, University of Dundee)

  • Michael L. J. Ashford

    (School of Medicine, University of Dundee)

  • Louise K. Modis

    (GlaxoSmithKline, Gunnelswood Road)

  • Gino Brunori

    (GlaxoSmithKline)

  • Daniel C. Sévin

    (Cellzome, GlaxoSmithKline R&D)

  • Padraic G. Fallon

    (School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin,)

  • Stuart T. Caldwell

    (WestCHEM School of Chemistry, University of Glasgow)

  • Edmund R. S. Kunji

    (MRC Mitochondrial Biology Unit, University of Cambridge,)

  • Edward T. Chouchani

    (Dana-Farber Cancer Institute, Harvard Medical School
    Harvard Medical School)

  • Christian Frezza

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre)

  • Albena T. Dinkova-Kostova

    (Jacqui Wood Cancer Centre, School of Medicine, University of Dundee
    Johns Hopkins University School of Medicine)

  • Richard C. Hartley

    (WestCHEM School of Chemistry, University of Glasgow)

  • Michael P. Murphy

    (MRC Mitochondrial Biology Unit, University of Cambridge,)

  • Luke A. O’Neill

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
    GlaxoSmithKline, Gunnelswood Road)

Abstract

WebTreatment of lipopolysaccharide-activated macrophages with the cell-permeable itaconate derivative 4-octyl itaconate activates the anti-inflammatory transcription factor Nrf2 by alkylating key cysteine residues on the KEAP1 protein.

Suggested Citation

  • Evanna L. Mills & Dylan G. Ryan & Hiran A. Prag & Dina Dikovskaya & Deepthi Menon & Zbigniew Zaslona & Mark P. Jedrychowski & Ana S. H. Costa & Maureen Higgins & Emily Hams & John Szpyt & Marah C. Run, 2018. "Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1," Nature, Nature, vol. 556(7699), pages 113-117, April.
    • Handle: RePEc:nat:nature:v:556:y:2018:i:7699:d:10.1038_nature25986
    DOI: 10.1038/nature25986
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    Cited by:

    1. Naziia Kurmasheva & Aida Said & Boaz Wong & Priscilla Kinderman & Xiaoying Han & Anna H. F. Rahimic & Alena Kress & Madalina E. Carter-Timofte & Emilia Holm & Demi Horst & Christoph F. Kollmann & Zhen, 2024. "Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways," Nature Communications, Nature, vol. 15(1), pages 1-28, December.

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