IPS-1, an adaptor triggering RIG-I-and Mda5-mediated type I interferon induction

T Kawai, K Takahashi, S Sato, C Coban, H Kumar… - Nature …, 2005 - nature.com
T Kawai, K Takahashi, S Sato, C Coban, H Kumar, H Kato, KJ Ishii, O Takeuchi, S Akira
Nature immunology, 2005nature.com
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-β promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon
and interferon-inducible genes through activation of IRF3, IRF7 and NF-κB 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 …
Abstract
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-β promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-κB 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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