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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Nature 2006, PMID: 16306936

Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response.

Oganesyan, Gagik; Saha, Supriya K; Guo, Beichu; He, Jeannie Q; Shahangian, Arash; Zarnegar, Brian; Perry, Andrea; Cheng, Genhong

Type I interferon (IFN) production is a critical component of the innate defence against viral infections. Viral products induce strong type I IFN responses through the activation of Toll-like receptors (TLRs) and intracellular cytoplasmic receptors such as protein kinase R (PKR). Here we demonstrate that cells lacking TRAF3, a member of the TNF receptor-associated factor family, are defective in type I IFN responses activated by several different TLRs. Furthermore, we show that TRAF3 associates with the TLR adaptors TRIF and IRAK1, as well as downstream IRF3/7 kinases TBK1 and IKK-epsilon, suggesting that TRAF3 serves as a critical link between TLR adaptors and downstream regulatory kinases important for IRF activation. In addition to TLR stimulation, we also show that TRAF3-deficient fibroblasts are defective in their type I IFN response to direct infection with vesicular stomatitis virus, indicating that TRAF3 is also an important component of TLR-independent viral recognition pathways. Our data demonstrate that TRAF3 is a major regulator of type I IFN production and the innate antiviral response.

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

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Hprd Interaction: TRAF3 — TICAM1 (in vivo)
  • Reactome Reaction: TBK1 → TMEM173 (indirect_complex)
  • Reactome Reaction: CD14 → TRAF3 (indirect_complex)
  • Reactome Reaction: IKBKE → IFIH1 (indirect_complex)
  • Reactome Reaction: TRAF3 → MAVS (indirect_complex)
  • Reactome Reaction: IRF3 → TMEM173 (reaction)
  • Reactome Reaction: TRAF3 → RNF135 (reaction)
  • Reactome Reaction: TRAF3 → IFIH1 (reaction)
  • Reactome Reaction: TRAF3 → TICAM2 (indirect_complex)
  • Reactome Reaction: LY96 → TRAF3 (reaction)
  • Reactome Reaction: IKBKE → DDX58 (reaction)
  • Reactome Reaction: TLR3 → TRAF3 (indirect_complex)
  • Reactome Reaction: IFIH1 → SIKE1 (reaction)
  • Reactome Reaction: TRIM25 → TBK1 (indirect_complex)
  • Reactome Reaction: IKBKE → MAVS (indirect_complex)
  • Reactome Reaction: RNF135 → SIKE1 (reaction)
  • Reactome Reaction: TBK1 → IFIH1 (indirect_complex)
  • Reactome Reaction: IRF3 → TMEM173 (indirect_complex)
  • Reactome Reaction: TBK1 → IFIH1 (reaction)
  • Reactome Reaction: IRF3 → TBK1 (reaction)
  • Reactome Reaction: MAVS → SIKE1 (reaction)
  • Reactome Reaction: IRF3 → TBK1 (direct_complex)
  • Reactome Reaction: TRAF3 → TICAM2 (reaction)
  • Reactome Reaction: CD14 → TRAF3 (reaction)
  • Reactome Reaction: TLR3 → TRAF3 (reaction)
  • Reactome Reaction: TBK1 → SIKE1 (reaction)
  • Reactome Reaction: TRAF3 → MAVS (reaction)
  • Reactome Reaction: TBK1 → DDX58 (indirect_complex)
  • Reactome Reaction: DDX58 → SIKE1 (reaction)
  • Reactome Reaction: IKBKE → TRIM25 (reaction)
  • Reactome Reaction: TRAF3 → TBK1 (reaction)
  • Reactome Reaction: IKBKE → RNF135 (indirect_complex)
  • Reactome Reaction: TRAF3 → RNF135 (indirect_complex)
  • Reactome Reaction: TRAF3 → DDX58 (indirect_complex)
  • Reactome Reaction: TRAF3 → TICAM1 (indirect_complex)
  • Reactome Reaction: IKBKE → RNF135 (reaction)
  • Reactome Reaction: IKBKE → DDX58 (indirect_complex)
  • Reactome Reaction: TRAF3 → TICAM1 (reaction)
  • Reactome Reaction: TRIM25 → SIKE1 (reaction)
  • Reactome Reaction: IKBKE → IFIH1 (reaction)
  • Reactome Reaction: IKBKE → TRAF3 (indirect_complex)
  • Reactome Reaction: TRAF3 → DDX58 (reaction)
  • Reactome Reaction: TBK1 → TMEM173 (reaction)
  • Reactome Reaction: TRAF3 → TRIM25 (indirect_complex)
  • Reactome Reaction: MAVS → TBK1 (indirect_complex)
  • Reactome Reaction: TRAF3 → IFIH1 (indirect_complex)
  • Reactome Reaction: MAVS → TBK1 (reaction)
  • Reactome Reaction: IKBKE → TRIM25 (indirect_complex)
  • Reactome Reaction: TRIM25 → TBK1 (reaction)
  • Reactome Reaction: TBK1 → RNF135 (indirect_complex)
  • Reactome Reaction: TBK1 → RNF135 (reaction)
  • Reactome Reaction: TRAF3 → TBK1 (indirect_complex)
  • Reactome Reaction: TLR4 → TRAF3 (reaction)
  • Reactome Reaction: TLR4 → TRAF3 (indirect_complex)
  • Reactome Reaction: TBK1 → DDX58 (reaction)
  • Reactome Reaction: IKBKE → SIKE1 (reaction)
  • Reactome Reaction: IKBKE → MAVS (reaction)
  • Reactome Reaction: TRAF3 → SIKE1 (reaction)
  • Reactome Reaction: TRAF3 → TRIM25 (reaction)
  • Reactome Reaction: IKBKE → TRAF3 (reaction)
  • Reactome Reaction: LY96 → TRAF3 (indirect_complex)
In total, 34 gene pairs are associated to this article in curated databases