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Publication : The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells.

First Author  Zhang Z Year  2011
Journal  Nat Immunol Volume  12
Issue  10 Pages  959-65
PubMed ID  21892174 Mgi Jnum  J:176439
Mgi Id  MGI:5291856 Doi  10.1038/ni.2091
Citation  Zhang Z, et al. (2011) The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol 12(10):959-65
abstractText  The recognition of pathogenic DNA is important to the initiation of antiviral responses. Here we report the identification of DDX41, a member of the DEXDc family of helicases, as an intracellular DNA sensor in myeloid dendritic cells (mDCs). Knockdown of DDX41 expression by short hairpin RNA blocked the ability of mDCs to mount type I interferon and cytokine responses to DNA and DNA viruses. Overexpression of both DDX41 and the membrane-associated adaptor STING together had a synergistic effect in promoting Ifnb promoter activity. DDX41 bound both DNA and STING and localized together with STING in the cytosol. Knockdown of DDX41 expression blocked activation of the mitogen-activated protein kinase TBK1 and the transcription factors NF-kappaB and IRF3 by B-form DNA. Our results suggest that DDX41 is an additional DNA sensor that depends on STING to sense pathogenic DNA.
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