Literature DB >> 25765883

Molecular cloning and functional characterization of porcine cyclic GMP-AMP synthase.

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.
Copyright © 2015 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Interferon; PRV; Porcine; cGAS

Mesh:

Substances:

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


  12 in total

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Journal:  Redox Biol       Date:  2020-06-08       Impact factor: 11.799

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