Nature 2006,
PMID: 16306936
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
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Text Mining Data
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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