| Literature DB >> 25765883 |
Jiang Wang1, Beibei Chu2, Lili Du1, Yingqian Han1, Xuemei Zhang1, Shuangshuang Fan1, Yueying Wang1, Guoyu Yang3.
Abstract
Cyclic GMP-AMP synthase (cGAS), which belongs to the nucleotidyltransferase family, recognizes cytosolic DNA and induces the type I interferon (IFN) pathway through the synthesis of the second messenger cGAMP. In this study, porcine cGAS (p-cGAS) was identified and its tissue distribution, subcellular localization, and functions in innate immunity were characterized. The coding sequence of p-cGAS is 1494 bp long, encodes 497 amino acids, and is most similar (74%) to Bos taurus cGAS. p-cGAS mRNA is abundant in the spleen, duodenum, jejunum, and ileum. The subcellular distribution of p-cGAS is not only in the cytosol, but also on the endoplasmic reticulum (ER) membrane. The overexpression of wild-type p-cGAS in porcine kidney epithelial cells, but not its catalytically inactive mutants, induced IFN-β expression, which was dependent on STING and IRF3. However, the downregulation of p-cGAS by RNA interference markedly reduced IFN-β expression after pseudorabies virus (PRV) infection or poly(dA:dT) transfection. These results demonstrate that p-cGAS is an important DNA sensor, required for IFN-β activation.Entities:
Keywords: Interferon; PRV; Porcine; cGAS
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Year: 2015 PMID: 25765883 DOI: 10.1016/j.molimm.2015.02.002
Source DB: PubMed Journal: Mol Immunol ISSN: 0161-5890 Impact factor: 4.407