著作: [茂谷 康]/[小迫 英尊]/Activation of stimulator of interferon genes (STING) induces ADAM17-mediated shedding of the immune semaphorin SEMA4D./[The Journal of Biological Chemistry]
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削除する| 種別 | 必須 | 学術論文(審査論文) | |||
|---|---|---|---|---|---|
| 言語 | 必須 | 英語 | |||
| 招待 | 推奨 | ||||
| 審査 | 推奨 | ||||
| カテゴリ | 推奨 | ||||
| 共著種別 | 推奨 | ||||
| 学究種別 | 推奨 | ||||
| 組織 | 推奨 | ||||
| 著者 | 必須 | ||||
| 題名 | 必須 |
(英) Activation of stimulator of interferon genes (STING) induces ADAM17-mediated shedding of the immune semaphorin SEMA4D. |
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| 副題 | 任意 | ||||
| 要約 | 任意 |
(英) Stimulator of interferon genes (STING) is an endoplasmic reticulum-resident membrane protein that mediates cytosolic pathogen DNA-induced innate immunity and inflammatory responses in host defenses. STING is activated by cyclic di-nucleotides and is then translocated to the Golgi apparatus, an event that triggers STING assembly with the downstream enzyme TANK-binding kinase 1 (TBK1). This assembly leads to the phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3), which in turn induces expression of type-I interferon (IFN) and chemokine genes. STING also mediates inflammatory responses independently of IRF3, but these molecular pathways are largely unexplored. Here, we analyzed the RAW264.7 macrophage secretome to comprehensively identify proinflammatory factors released into the extracellular medium upon STING activation. In total, we identified 1299 proteins in macrophage culture supernatants, of which 23 were significantly increased after STING activation. These proteins included IRF3-dependent cytokines, as well as previously unknown targets of STING, such as the immune semaphorin SEMA4D/CD100, which possesses proinflammatory cytokine-like activities. Unlike for canonical cytokines, the expression of the SEMA4D gene was not up-regulated. Instead, upon STING activation, membrane-bound SEMA4D was cleaved into a soluble form, suggesting the presence of a post-translational shedding machinery. Importantly, the SEMA4D shedding was blocked by TMI-1, an inhibitor of the sheddase ADAM metallopeptidase domain 17 (ADAM17) but not by the TBK1 inhibitor BX795. These results suggest that STING activates ADAM17 and that this activation produces soluble proinflammatory SEMA4D independently of the TBK1/IRF3-mediated transcriptional pathway. |
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| キーワード | 推奨 | ||||
| 発行所 | 推奨 | ||||
| 誌名 | 必須 |
The Journal of Biological Chemistry([The American Society for Biochemistry and Molecular Biology])
(pISSN: 0021-9258, eISSN: 1083-351X)
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| 巻 | 必須 | 293 | |||
| 号 | 必須 | 20 | |||
| 頁 | 必須 | 7717 7726 | |||
| 都市 | 任意 | ||||
| 年月日 | 必須 | 2018年 4月 4日 | |||
| URL | 任意 | ||||
| DOI | 任意 | 10.1074/jbc.RA118.002175 (→Scopusで検索) | |||
| PMID | 任意 | 29618514 (→Scopusで検索) | |||
| CRID | 任意 | ||||
| Scopus | 任意 | ||||
| researchmap | 任意 | ||||
| 評価値 | 任意 | ||||
| 被引用数 | 任意 | ||||
| 指導教員 | 推奨 | ||||
| 備考 | 任意 |
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