[Role of IPS-1 in type I IFN induction].
Type I interferons (IFNalpha/beta) are central mediators for antiviral responses. Using a functional cloning strategy, we have identified a molecule designated IPS-1. IPS-1 overexpression caused antiviral responses by producing type I IFN and IFN-inducible genes through activation of IRF3, IRF7 and NF-kappaB. TBK1 and IKKi protein kinases were required for the IPS-1-mediated IFN induction. IPS-1 contains an N-terminal caspase recruiting domain (CARD)-like structure that mediates interaction with the CARD of RIG-I and Mda5, cytoplasmic RNA helicases sensing RNA viruses. Reduction of IPS-1 by siRNA blocked IFN induction by virus infection. Thus, IPS-1 is an adapter that mediates RIG-I- and Mda5-dependent antiviral responses.
Kawai
Taro
T
Akira Innate Immunity Project, ERATO, JST.
Akira
Shizuo
S
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000502:physiology*; D003001:Cloning, Molecular; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D006801:Humans; D051550:I-kappa B Kinase; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis*; D000072640:Interferon-Induced Helicase, IFIH1; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D020365:RNA Helicases / Q000502:physiology; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014777:Virus Diseases / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; C505371:MAVS protein, human; D011971:Receptors, Immunologic; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases