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

• Published in: Nature Immunology 2005-10, Vol.6 (10), p.981-988
• Main Authors: Akira, Shizuo, Kawai, Taro, Takahashi, Ken, Sato, Shintaro, Coban, Cevayir, Kumar, Himanshu, Kato, Hiroki, Ishii, Ken J, Takeuchi, Osamu
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Animals; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; DEAD Box Protein 58; DEAD-box RNA Helicases; DNA-Binding Proteins - metabolism; Humans; I-kappa B Kinase; Immunology; Infectious Diseases; Interferon Inducers - metabolism; Interferon Regulatory Factor-3; Interferon Regulatory Factor-7; Interferon Type I - biosynthesis; Interferon-beta - genetics; Interferon-Induced Helicase, IFIH1; Mice; Molecular Sequence Data; NF-kappa B - metabolism; Protein Serine-Threonine Kinases - physiology; Protein Structure, Tertiary; Receptors, Immunologic; RNA Helicases - metabolism; RNA, Messenger - genetics; Sequence Alignment; Transcription Factors - metabolism; Vesicular stomatitis Indiana virus - immunology; Vesicular stomatitis Indiana virus - physiology
• ISSN: 1529-2908; 1529-2916; 1365-2567
• DOI: 10.1038/ni1243

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.