2. Academic Validation
  3. Activation of STING requires palmitoylation at the Golgi

Activation of STING requires palmitoylation at the Golgi

  • Nat Commun. 2016 Jun 21:7:11932. doi: 10.1038/ncomms11932.
Kojiro Mukai 1 2,  Hiroyasu Konno 3,  Tatsuya Akiba 1,  Takefumi Uemura 4,  Satoshi Waguri 4,  Toshihide Kobayashi 2,  Glen N Barber 3,  Hiroyuki Arai 1 5,  Tomohiko Taguchi 1 5
Affiliations

Affiliations

  • 1 Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • 2 Lipid Biology Laboratory, RIKEN, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.
  • 3 Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
  • 4 Department of Anatomy and Histology, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima 960-1295, Japan.
  • 5 Pathological Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
PMID: 27324217 DOI: 10.1038/ncomms11932
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.

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