論文 - 詳細
| RRC ID | 47252 |
|---|---|
| 著者 | Mukai K, Konno H, Akiba T, Uemura T, Waguri S, Kobayashi T, Barber GN, Arai H, Taguchi T. |
| タイトル | Activation of STING requires palmitoylation at the Golgi. |
| ジャーナル | Nat Commun |
| 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. |
| 巻・号 | 7 |
| ページ | 11932 |
| 公開日 | 2016-6-21 |
| DOI | 10.1038/ncomms11932 |
| PII | ncomms11932 |
| PMID | 27324217 |
| PMC | PMC4919521 |
| MeSH | Animals COS Cells Chlorocebus aethiops Embryo, Mammalian Endoplasmic Reticulum / immunology Endoplasmic Reticulum / metabolism Fibroblasts / immunology* Fibroblasts / virology Gene Expression Regulation Golgi Apparatus / immunology Golgi Apparatus / metabolism* HEK293 Cells Herpesvirus 1, Human / growth & development Herpesvirus 1, Human / immunology Humans Immunity, Innate* Interferon Type I / genetics* Interferon Type I / immunology Lipoylation Membrane Proteins / agonists Membrane Proteins / antagonists & inhibitors Membrane Proteins / genetics* Membrane Proteins / immunology Mice Mutation Palmitates / pharmacology Primary Cell Culture Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / immunology Protein Transport Xanthones / pharmacology |
| IF | 12.121 |
| 引用数 | 87 |
| WOS 分野 | IMMUNOLOGY |
| リソース情報 | |
| 遺伝子材料 | pBabe-hSTING(WT) (RDB14351) pBabe-hSTING(C88/91S) (RDB14352) pBabe-hSTING(V147L) (RDB14353) pBabe-hSTING(N154S) (RDB14354) pBabe-hSTING(V155M) (RDB14355) pBabe-hSTING(V147L_C88S_C91S) (RDB14356) pBabe-hSTING(N154S_C88S_C91S) (RDB14357) pBabe-hSTING(V155M_C88S_C91S) (RDB14358). |