Activation of STING requires palmitoylation at the Golgi
| Autor: | Takefumi Uemura, Tatsuya Akiba, Kojiro Mukai, Hiroyuki Arai, Satoshi Waguri, Toshihide Kobayashi, Hiroyasu Konno, Tomohiko Taguchi, Glen N. Barber |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Science Lipoylation Xanthones Primary Cell Culture Palmitates General Physics and Astronomy Golgi Apparatus Herpesvirus 1 Human Biology Protein Serine-Threonine Kinases medicine.disease_cause Endoplasmic Reticulum General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences symbols.namesake Mice Palmitoylation Interferon Chlorocebus aethiops medicine Animals Humans Mutation Multidisciplinary Endoplasmic reticulum Membrane Proteins General Chemistry Golgi apparatus Fibroblasts Embryo Mammalian Virology eye diseases Immunity Innate Cell biology Sting Protein Transport 030104 developmental biology HEK293 Cells Gene Expression Regulation Stimulator of interferon genes COS Cells Interferon Type I symbols Interferon type I medicine.drug |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-10 (2016) |
| ISSN: | 2041-1723 |
| Popis: | 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. STING is essential for the type I interferon immune response to foreign DNA. Here, the authors show that palmitoylation of STING at the Golgi is required for activating downstream signalling, and increased Golgi localization of certain STING variants may cause autoimmune disease in some cases. |
| Databáze: | OpenAIRE |
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