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dc.contributor.author | Kuchitsu, Yoshihiko | en |
dc.contributor.author | Mukai, Kojiro | en |
dc.contributor.author | Uematsu, Rei | en |
dc.contributor.author | Takaada, Yuki | en |
dc.contributor.author | Shinojima, Ayumi | en |
dc.contributor.author | Shindo, Ruri | en |
dc.contributor.author | Shoji, Tsumugi | en |
dc.contributor.author | Hamano, Shiori | en |
dc.contributor.author | Ogawa, Emari | en |
dc.contributor.author | Sato, Ryota | en |
dc.contributor.author | Miyake, Kensuke | en |
dc.contributor.author | Kato, Akihisa | en |
dc.contributor.author | Kawaguchi, Yasushi | en |
dc.contributor.author | Nishitani-Isa, Masahiko | en |
dc.contributor.author | Izawa, Kazushi | en |
dc.contributor.author | Nishikomori, Ryuta | en |
dc.contributor.author | Yasumi, Takahiro | en |
dc.contributor.author | Suzuki, Takehiro | en |
dc.contributor.author | Dohmae, Naoshi | en |
dc.contributor.author | Uemura, Takefumi | en |
dc.contributor.author | Barber, Glen N. | en |
dc.contributor.author | Arai, Hiroyuki | en |
dc.contributor.author | Waguri, Satoshi | en |
dc.contributor.author | Taguchi, Tomohiko | en |
dc.contributor.alternative | 朽津, 芳彦 | ja |
dc.contributor.alternative | 向井, 康治朗 | ja |
dc.contributor.alternative | 植松, 黎 | ja |
dc.contributor.alternative | 高阿田, 有希 | ja |
dc.contributor.alternative | 篠島, あゆみ | ja |
dc.contributor.alternative | 進藤, 瑠璃 | ja |
dc.contributor.alternative | 東海林, 紬 | ja |
dc.contributor.alternative | 濱野, 栞里 | ja |
dc.contributor.alternative | 小川, 笑満里 | ja |
dc.contributor.alternative | 佐藤, 亮太 | ja |
dc.contributor.alternative | 三宅, 健介 | ja |
dc.contributor.alternative | 加藤, 哲久 | ja |
dc.contributor.alternative | 川口, 寧 | ja |
dc.contributor.alternative | 伊佐, 真彦 | ja |
dc.contributor.alternative | 井澤, 和司 | ja |
dc.contributor.alternative | 西小森, 隆太 | ja |
dc.contributor.alternative | 八角, 高裕 | ja |
dc.contributor.alternative | 鈴木, 健裕 | ja |
dc.contributor.alternative | 堂前, 直 | ja |
dc.contributor.alternative | 植村, 武文 | ja |
dc.contributor.alternative | 新井, 博之 | ja |
dc.contributor.alternative | 和栗, 聡 | ja |
dc.contributor.alternative | 田口, 友彦 | ja |
dc.date.accessioned | 2023-03-22T01:58:25Z | - |
dc.date.available | 2023-03-22T01:58:25Z | - |
dc.date.issued | 2023-03 | - |
dc.identifier.uri | http://hdl.handle.net/2433/279876 | - |
dc.description | STING炎症シグナルの終結分子機構 --新規細胞内分解システムの発見--. 京都大学プレスリリース. 2023-03-14. | ja |
dc.description.abstract | Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs. | en |
dc.language.iso | eng | - |
dc.publisher | Springer Nature | en |
dc.rights | © The Author(s) 2023 | en |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | Autophagy | en |
dc.subject | ESCRT | en |
dc.subject | Innate immunity | en |
dc.subject | Lysosomes | en |
dc.title | STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Nature Cell Biology | en |
dc.identifier.volume | 25 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 453 | - |
dc.identifier.epage | 466 | - |
dc.relation.doi | 10.1038/s41556-023-01098-9 | - |
dc.textversion | publisher | - |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.address | Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo | en |
dc.address | Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo | en |
dc.address | Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo | en |
dc.address | Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo; Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo | en |
dc.address | Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo; Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo | en |
dc.address | Department of Pediatrics, Kyoto University Graduate School of Medicine | en |
dc.address | Department of Pediatrics, Kyoto University Graduate School of Medicine | en |
dc.address | Department of Pediatrics and Child Health, Kurume University School of Medicine | en |
dc.address | Department of Pediatrics, Kyoto University Graduate School of Medicine | en |
dc.address | Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science | en |
dc.address | Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science | en |
dc.address | Department of Anatomy and Histology, Fukushima Medical University School of Medicine | en |
dc.address | Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine | en |
dc.address | Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo | en |
dc.address | Department of Anatomy and Histology, Fukushima Medical University School of Medicine | en |
dc.address | Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University | en |
dc.identifier.pmid | 36918692 | - |
dc.relation.url | https://www.kyoto-u.ac.jp/ja/research-news/2023-03-14-1 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 19H00974 | - |
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datacite.awardNumber | 21K15464 | - |
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dc.identifier.pissn | 1465-7392 | - |
dc.identifier.eissn | 1476-4679 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.awardTitle | 細胞内輸送が厳密に制御する自然免疫分子STINGの活性・不活性化の分子機構 | ja |
jpcoar.awardTitle | オルガネラ膜特異的脂質環境の細胞内情報発信プラットフォームとしての新機能の解明 | ja |
jpcoar.awardTitle | 膜脂質を基軸としたオルガネラ連携ゾーンの解明 | ja |
jpcoar.awardTitle | p62変異による液-液相分離異常の微細形態とその分子基盤 | ja |
jpcoar.awardTitle | 哺乳動物におけるミクロオートファジーを介した細胞内タンパク質の分解機構 | ja |
jpcoar.awardTitle | 自然免疫分子STINGのオルガネラ局在に応じた活性制御機構とその破綻による疾患 | ja |
jpcoar.awardTitle | STINGを介したI型インターフェロン応答の収束機構の解明 | ja |
jpcoar.awardTitle | エンドソーム上でEGFRの分解・リサイクルを決定する新規分子基盤 | ja |
jpcoar.awardTitle | HSV感染におけるTLR3リガンドの探索およびヌクレアーゼによる応答制御機構解明 | ja |
jpcoar.awardTitle | ヘルペスウイルスの増殖・病態発現に関する統合的分子基盤 | ja |
出現コレクション: | 学術雑誌掲載論文等 |
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