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

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-beta promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-kappaB 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.

Pubmed ID: 16127453

Authors

  • Kawai T
  • Takahashi K
  • Sato S
  • Coban C
  • Kumar H
  • Kato H
  • Ishii KJ
  • Takeuchi O
  • Akira S

Journal

Nature immunology

Publication Data

October 22, 2005

Associated Grants

None

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • DEAD-box RNA Helicases
  • DNA-Binding Proteins
  • Humans
  • I-kappa B Kinase
  • Interferon Inducers
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Interferon-beta
  • Mice
  • Molecular Sequence Data
  • NF-kappa B
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • RNA Helicases
  • RNA, Messenger
  • Sequence Alignment
  • Transcription Factors
  • Vesicular stomatitis Indiana virus