학술논문

The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response.
Document Type
Article
Source
EMBO Journal. 8/13/2008, Vol. 27 Issue 15, p2135-2146. 12p. 1 Diagram, 7 Graphs.
Subject
*PROTEIN binding
*BIOCHEMISTRY
*ALLOSTERIC proteins
*PROTEIN kinases
*PHOSPHOTRANSFERASES
*PATHOGENIC microorganisms
Language
ISSN
0261-4189
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. [ABSTRACT FROM AUTHOR]