Cell Mol Biol Incl Cyto Enzymol 2006,
PMID: 16914100
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
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Text Mining Data
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Manually curated Databases
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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