Article
- The EMBO Journal (2008) 27, 2135 - 2146
- doi:10.1038/emboj.2008.126
Published online: 26 June 2008
Subject Categories:
The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune responseEMBO Open
Didier Soulat1,a, Tilmann Bürckstümmer2,a, Sandra Westermayer1, Adriana Goncalves2, Angela Bauch2, Adrijana Stefanovic2, Oliver Hantschel2, Keiryn L Bennett2, Thomas Decker1 and Giulio Superti-Furga2
- Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria
- Director's Laboratory, Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
Correspondence to:
Thomas Decker, Max F Perutz Laboratories, Dr Bohr-Gasse 9/4, 1030 Vienna, Austria. Tel.: +43 1 427 754 605; E-mail: thomas.decker@univie.ac.at
Giulio Superti-Furga, Director's Laboratory, CeMM, Research Center for Molecular Medicine, Lazarettgasse 19, 1090 Vienna, Austria. Tel.: +43 1 401 607 0001; Fax: +43 1 401 609 70000; E-mail: gsuperti@cemm.oeaw.ac.at
aThese authors contributed equally to this work
Received 27 March 2008; Accepted 4 June 2008
Abstract
TANK-binding kinase 1 (TBK1) is of central importance for the induction of type-I interferon (IFN) in response to pathogens. We identified the DEAD-box helicase DDX3X as an interaction partner of TBK1. TBK1 and DDX3X acted synergistically in their ability to stimulate the IFN promoter, whereas RNAi-mediated reduction of DDX3X expression led to an impairment of IFN production. Chromatin immunoprecipitation indicated that DDX3X is recruited to the IFN promoter upon infection with Listeria monocytogenes, suggesting a transcriptional mechanism of action. DDX3X was found to be a TBK1 substrate in vitro and in vivo. Phosphorylation-deficient mutants of DDX3X failed to synergize with TBK1 in their ability to stimulate the IFN promoter. Overall, our data imply that DDX3X is a critical effector of TBK1 that is necessary for type I IFN induction.
Keywords:
- DDX3X,
- innate immunity,
- interferon,
- phosphorylation,
- TBK1
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