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Hokkaido University Collection of Scholarly and Academic Papers >
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Cell Type-Specific Subcellular Localization of Phospho-TBK1 in Response to Cytoplasmic Viral DNA
This item is licensed under:Creative Commons Attribution 3.0 Unported
| Title: | Cell Type-Specific Subcellular Localization of Phospho-TBK1 in Response to Cytoplasmic Viral DNA |
| Authors: | Suzuki, Takayuki Browse this author | | Oshiumi, Hiroyuki Browse this author →KAKEN DB | | Miyashita, Moeko Browse this author | | Aly, Hussein Hassan Browse this author | | Matsumoto, Misako Browse this author →KAKEN DB | | Seya, Tsukasa Browse this author →KAKEN DB |
| Issue Date: | 9-Dec-2013 |
| Publisher: | Public library science |
| Journal Title: | Plos one |
| Volume: | 8 |
| Issue: | 12 |
| Start Page: | e83639 |
| Publisher DOI: | 10.1371/journal.pone.0083639 |
| PMID: | 24349538 |
| Abstract: | Cytoplasmic viral RNA and DNA are recognized by RIG-I-like receptors and DNA sensors that include DAI, IFI16, DDX41, and cGAS. The RNA and DNA sensors evoke innate immune responses through the IPS-1 and STING adaptors. IPS-1 and STING activate TBK1 kinase. TBK1 is phosphorylated in its activation loop, leading to IRF3/7 activation and Type I interferon (IFN) production. IPS-1 and STING localize to the mitochondria and endoplasmic reticulum, respectively, whereas it is unclear where phosphorylated TBK1 is localized in response to cytoplasmic viral DNA. Here, we investigated phospho-TBK1 (p-TBK1) subcellular localization using a p-TBK1-specific antibody. Stimulation with vertebrate DNA by transfection increased p-TBK1 levels. Interestingly, stimulation-induced p-TBK1 exhibited mitochondrial localization in HeLa and HepG2 cells and colocalized with mitochondrial IPS-1 and MFN-1. Hepatitis B virus DNA stimulation or herpes simplex virus type-1 infection also induced p-TBK1 mitochondrial localization in HeLa cells, indicating that cytoplasmic viral DNA induces p-TBK1 mitochondrial localization in HeLa cells. In contrast, p-TBK1 did not show mitochondrial localization in RAW264.7, L929, or T-23 cells, and most of p-TBK1 colocalized with STING in response to cytoplasmic DNA in those mammalian cells, indicating cell type-specific localization of p-TBK1 in response to cytoplasmic viral DNA. A previous knockout study showed that mouse IPS-1 was dispensable for Type I IFN production in response to cytoplasmic DNA. However, we found that knockdown of IPS-1 markedly reduced p-TBK1 levels in HeLa cells. Taken together, our data elucidated the cell type-specific subcellular localization of p-TBK1 and a cell type-specific role of IPS-1 in TBK1 activation in response to cytoplasmic viral DNA. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/54682 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 押海 裕之
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