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Activation of STING requires palmitoylation at the Golgi

Author

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  • Kojiro Mukai

    (Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
    Lipid Biology Laboratory, RIKEN)

  • Hiroyasu Konno

    (University of Miami School of Medicine)

  • Tatsuya Akiba

    (Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan)

  • Takefumi Uemura

    (Fukushima Medical University School of Medicine, Hikarigaoka)

  • Satoshi Waguri

    (Fukushima Medical University School of Medicine, Hikarigaoka)

  • Toshihide Kobayashi

    (Lipid Biology Laboratory, RIKEN)

  • Glen N. Barber

    (University of Miami School of Medicine)

  • Hiroyuki Arai

    (Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
    Pathological Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, University of Tokyo)

  • Tomohiko Taguchi

    (Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
    Pathological Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, University of Tokyo)

Abstract

Stimulator of interferon genes (STING) is essential for the type I interferon response against DNA pathogens. In response to the presence of DNA and/or cyclic dinucleotides, STING translocates from the endoplasmic reticulum to perinuclear compartments. However, the role of this subcellular translocation remains poorly defined. Here we show that palmitoylation of STING at the Golgi is essential for activation of STING. Treatment with palmitoylation inhibitor 2-bromopalmitate (2-BP) suppresses palmitoylation of STING and abolishes the type I interferon response. Mutation of two membrane-proximal Cys residues (Cys88/91) suppresses palmitoylation, and this STING mutant cannot induce STING-dependent host defense genes. STING variants that constitutively induce the type I interferon response were found in patients with autoimmune diseases. The response elicited by these STING variants is effectively inhibited by 2-BP or an introduction of Cys88/91Ser mutation. Our results may lead to new treatments for cytosolic DNA-triggered autoinflammatory diseases.

Suggested Citation

  • Kojiro Mukai & Hiroyasu Konno & Tatsuya Akiba & Takefumi Uemura & Satoshi Waguri & Toshihide Kobayashi & Glen N. Barber & Hiroyuki Arai & Tomohiko Taguchi, 2016. "Activation of STING requires palmitoylation at the Golgi," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11932
    DOI: 10.1038/ncomms11932
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