Activation of STING requires palmitoylation at the Golgi

Kojiro Mukai, Hiroyasu Konno, Tatsuya Akiba, Takefumi Uemura, Satoshi Waguri, Toshihide Kobayashi, Glen N. Barber, Hiroyuki Arai, Tomohiko Taguchi

Research output: Contribution to journalArticle

84 Scopus citations

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.

Original languageEnglish (US)
Article number11932
JournalNature communications
Volume7
DOIs
StatePublished - Jun 21 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Mukai, K., Konno, H., Akiba, T., Uemura, T., Waguri, S., Kobayashi, T., Barber, G. N., Arai, H., & Taguchi, T. (2016). Activation of STING requires palmitoylation at the Golgi. Nature communications, 7, [11932]. https://doi.org/10.1038/ncomms11932