Gene interactions and pathways from curated databases and text-mining
Cell Mol Biol Incl Cyto Enzymol 2006, PMID: 16914100

Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway.

Paz, S; Sun, Q; Nakhaei, P; Romieu-Mourez, R; Goubau, D; Julkunen, I; Lin, R; Hiscott, J

The induction of type I interferon (IFN) and the development of the innate antiviral response are mediated by the activation of interferon regulatory factor (IRF)-3 and IRF-7 under the control of the non-canonical kinases TBK-1 and IKKepsilon. The initial sensing of infection by RNA viruses is mediated by the cytoplasmic, retinoic acid inducible gene I (RIG-I), via a Toll-like receptor (TLR) independent signaling pathway. In the present study, we identify key residues involved in IRF-3 and IRF-7 phosphorylation using TAP-tag purification of TBK-1 and IKKepsilon proteins. Based on the identification of an extended sequence motif--SxSxxxS--common to both IRF-3 and IRF-7, an IRF-7 pSer477/479 phosphospecific antibody was generated. Virus infection, TBK-1/IKKepsilon expression or co-expression of different signaling adaptors such as RIG-I, MAVS and TRIF, all stimulated pSer477/479 phosphorylation. Furthermore, the newly identified adaptor of the RIG-I pathway (MAVS/IPS-1/VISA/Cardif) was able to induce IRF and NF-kappaB dependent promoter activity as efficiently as the constitutively active form of RIG-I (DeltaRIG-I). Co-expression of the NS3/4A protease activity of hepatitis C virus however blocked MAVS-mediated gene activation in a dose dependent manner. These studies link RIG-I sensing of viral RNA to downstream kinase signaling and phosphorylation of IRF-3 and IRF-7 via the MAVS/IPS/VISA/Cardif adaptor.

Diseases/Pathways annotated by Medline MESH: Flaviviridae Infections
Document information provided by NCBI PubMed

Text Mining Data

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Manually curated Databases

  • Reactome Reaction: IFIH1 → RNF135 (reaction)
  • Reactome Reaction: TRAF3 → RNF135 (reaction)
  • Reactome Reaction: TRAF3 → IFIH1 (reaction)
  • Reactome Reaction: TANK → MAVS (reaction)
  • Reactome Reaction: TRAF2 → TRIM25 (reaction)
  • Reactome Reaction: IKBKE → IRF3 (reaction)
  • Reactome Reaction: TRAF2 → MAVS (reaction)
  • Reactome Reaction: IKBKE → TBK1 (reaction)
  • Reactome Reaction: IKBKE → DDX58 (reaction)
  • Reactome Reaction: IRF7 → TANK (reaction)
  • Reactome Reaction: MAVS → DDX58 (reaction)
  • Reactome Reaction: DDX58 → IFIH1 (reaction)
  • Reactome Reaction: TBK1 → TBK1 (reaction)
  • Reactome Reaction: TANK → TRIM25 (reaction)
  • Reactome Reaction: IRF7 → IRF7 (reaction)
  • Reactome Reaction: IKBKE → IRF7 (reaction)
  • Reactome Reaction: IRF3 → DDX58 (reaction)
  • Reactome Reaction: IRF7 → TRAF3 (reaction)
  • Reactome Reaction: MAVS → MAVS (reaction)
  • Reactome Reaction: DDX58 → DDX58 (reaction)
  • Reactome Reaction: TRIM25 → MAVS (reaction)
  • Reactome Reaction: TRAF2 → RNF135 (reaction)
  • Reactome Reaction: TBK1 → IFIH1 (reaction)
  • Reactome Reaction: IRF3 → TRAF3 (reaction)
  • Reactome Reaction: IRF3 → TBK1 (reaction)
  • Reactome Reaction: IRF7 → IFIH1 (reaction)
  • Reactome Reaction: IKBKE → TANK (reaction)
  • Reactome Reaction: TRIM25 → DDX58 (reaction)
  • Reactome Reaction: IRF7 → TRAF6 (reaction)
  • Reactome Reaction: IRF3 → MAVS (reaction)
  • Reactome Reaction: IKBKE → IKBKE (reaction)
  • Reactome Reaction: TRAF3 → MAVS (reaction)
  • Reactome Reaction: TANK → DDX58 (reaction)
  • Reactome Reaction: IKBKE → TRIM25 (reaction)
  • Reactome Reaction: TRAF3 → TBK1 (reaction)
  • Reactome Reaction: IRF7 → RNF135 (reaction)
  • Reactome Reaction: IRF3 → TRIM25 (reaction)
  • Reactome Reaction: TRIM25 → TRAF6 (reaction)
  • Reactome Reaction: IKBKE → RNF135 (reaction)
  • Reactome Reaction: TRAF3 → TRAF3 (reaction)
  • Reactome Reaction: TRAF6 → IFIH1 (reaction)
  • Reactome Reaction: TRAF2 → TRAF6 (reaction)
  • Reactome Reaction: IKBKE → IFIH1 (reaction)
  • Reactome Reaction: IRF3 → RNF135 (reaction)
  • Reactome Reaction: TANK → TBK1 (reaction)
  • Reactome Reaction: TRAF3 → DDX58 (reaction)
  • Reactome Reaction: TRAF6 → DDX58 (reaction)
  • Reactome Reaction: TRAF6 → TRAF6 (reaction)
  • Reactome Reaction: IRF3 → IRF3 (reaction)
  • Reactome Reaction: TRAF2 → DDX58 (reaction)
  • Reactome Reaction: MAVS → TBK1 (reaction)
  • Reactome Reaction: TRIM25 → IFIH1 (reaction)
  • Reactome Reaction: TRIM25 → TBK1 (reaction)
  • Reactome Reaction: TRAF2 → TRAF2 (reaction)
  • Reactome Reaction: IKBKE → TRAF6 (reaction)
  • Reactome Reaction: TRAF6 → TBK1 (reaction)
  • Reactome Reaction: TRAF6 → RNF135 (reaction)
  • Reactome Reaction: RNF135 → RNF135 (reaction)
  • Reactome Reaction: TANK → TRAF2 (reaction)
  • Reactome Reaction: TRAF6 → MAVS (reaction)
  • Reactome Reaction: TANK → IFIH1 (reaction)
  • Reactome Reaction: TRIM25 → TRIM25 (reaction)
  • Reactome Reaction: TANK → RNF135 (reaction)
  • Reactome Reaction: TRAF2 → TBK1 (reaction)
  • Reactome Reaction: IKBKE → TRAF2 (reaction)
  • Reactome Reaction: TRIM25 → RNF135 (reaction)
  • Reactome Reaction: TANK → TRAF6 (reaction)
  • Reactome Reaction: MAVS → RNF135 (reaction)
  • Reactome Reaction: TBK1 → RNF135 (reaction)
  • Reactome Reaction: DDX58 → RNF135 (reaction)
  • Reactome Reaction: IRF7 → TBK1 (reaction)
  • Reactome Reaction: IRF7 → DDX58 (reaction)
  • Reactome Reaction: TRAF2 → IFIH1 (reaction)
  • Reactome Reaction: TBK1 → DDX58 (reaction)
  • Reactome Reaction: IRF3 → IRF7 (reaction)
  • Reactome Reaction: IKBKE → MAVS (reaction)
  • Reactome Reaction: TRAF3 → TRIM25 (reaction)
  • Reactome Reaction: IRF7 → MAVS (reaction)
  • Reactome Reaction: IRF7 → TRAF2 (reaction)
  • Reactome Reaction: IRF3 → IFIH1 (reaction)
  • Reactome Reaction: MAVS → IFIH1 (reaction)
  • Reactome Reaction: IFIH1 → IFIH1 (reaction)
  • Reactome Reaction: IKBKE → TRAF3 (reaction)
  • Reactome Reaction: TANK → TANK (reaction)
  • Reactome Reaction: IRF7 → TRIM25 (reaction)
In total, 85 gene pairs are associated to this article in curated databases