We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-β-inducing potential.
- Authors
Oshiumi, Hiroyuki; Sakai, Keisuke; Matsumoto, Misako; Seya, Tsukasa
- Abstract
Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) are members of the DEAD box helicases, and recognize viral RNA in the cytoplasm, leading to IFN-β induction through the adaptor IFN-β promoter stimulator-1 (IPS-1) (also known as Cardif, mitochondrial antiviral signaling protein or virus-induced signaling adaptor). Since uninfected cells usually harbor a trace of RIG-I, other RNA-binding proteins may participate in assembling viral RNA into the IPS-1 pathway during the initial response to infection. We searched for proteins coupling with human IPS-1 by yeast two-hybrid and identified another DEAD (Asp-Glu-Ala-Asp) box helicase, DDX3 (DEAD/H BOX 3). DDX3 can bind viral RNA to join it in the IPS-1 complex. Unlike RIG-I, DDX3 was constitutively expressed in cells, and some fraction of DDX3 is colocalized with IPS-1 around mitochondria. The 622-662 a.a DDX3 C-terminal region (DDX3-C) directly bound to the IPS-1 CARD-like domain, and the whole DDX3 protein also associated with RLR. By reporter assay, DDX3 helped IPS-1 up-regulate IFN-β promoter activation and knockdown of DDX3 by siRNA resulted in reduced IFN-β induction. This activity was conserved on the DDX3-C fragment. DDX3 only marginally enhanced IFN-β promoter activation induced by transfected TANK-binding kinase 1 (TBK1) or I-kappa-B kinase-ε (IKKε). Forced expression of DDX3 augmented virus-mediated IFN-β induction and host cell protection against virus infection. Hence, DDX3 is an antiviral IPS-1 enhancer.
- Publication
European Journal of Immunology, 2010, Vol 40, Issue 4, p940
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200940203