Nature Immunology
6, 981 - 988 (2005)
Published online: 28 August 2005; | doi:10.1038/ni1243
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon inductionTaro Kawai1, Ken Takahashi2, 4, Shintaro Sato1, Cevayir Coban3, Himanshu Kumar2, Hiroki Kato2, Ken J Ishii1, Osamu Takeuchi1, 2
& Shizuo Akira1, 2, 31
Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. 2
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. 3
The 21st Century COE, Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. 4
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Sakyoku, Kyoto 606-8507, Japan.
Correspondence should be addressed to Shizuo Akira sakira@biken.osaka-u.ac.jp Type I interferons are central mediators for antiviral responses. Using high-throughput functional screening of interferon inducers, we have identified here a molecule we call interferon- promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF- B transcription factors. TBK1 and IKKi protein kinases were required for the IPS-1-mediated interferon induction. IPS-1 contained an N-terminal CARD-like structure that mediated interaction with the CARD of RIG-I and Mda5, which are cytoplasmic RNA helicases that sense viral infection. 'Knockdown' of IPS-1 by small interfering RNA blocked interferon induction by virus infection. Thus, IPS-1 is an adaptor involved in RIG-I- and Mda5-mediated antiviral immune responses.
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