Cell Type-Specific Subcellular Localization of Phospho-TBK1 in Response to Cytoplasmic Viral DNA

Suzuki, Takayuki; Oshiumi, Hiroyuki; Miyashita, Moeko; Aly, Hussein Hassan; Matsumoto, Misako; Seya, Tsukasa

Cell Type-Specific Subcellular Localization of Phospho-TBK1 in Response to Cytoplasmic Viral DNA

Suzuki, Takayuki; Oshiumi, Hiroyuki; Miyashita, Moeko et al.

Plos one, 2013, 8(12), e83639

Permalink : https://hdl.handle.net/2115/54682

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アクセス権	open access
URI	https://hdl.handle.net/2115/54682
タイトル	Cell Type-Specific Subcellular Localization of Phospho-TBK1 in Response to Cytoplasmic Viral DNA
著者	Suzuki, Takayuki ; Oshiumi, Hiroyuki ; Miyashita, Moeko ; Aly, Hussein Hassan ; Matsumoto, Misako ; Seya, Tsukasa
著者名 Suzuki, Takayuki
e-Rad_Researcher 50379103 著者名 Oshiumi, Hiroyuki
著者名 Miyashita, Moeko
著者名 Aly, Hussein Hassan
e-Rad_Researcher 30332456 著者名 Matsumoto, Misako
e-Rad_Researcher 10301805 著者名 Seya, Tsukasa
言語	英語
発行日	2013-12-09
出版者	Public library science
収録物名	Plos one
巻(号)	8(12)
ページ	e83639
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1932-6203
関連情報	PMID 24349538
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0083639