Phosphorylation and release of IRF3

Stable Identifier
R-HSA-1606327
Type
Reaction
Species
Homo sapiens
Related Species
Human alphaherpesvirus 2, Human cytomegalovirus
Compartment
cytosol
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Phosphorylation and release of IRF3
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IRF3 is activated through a two-step phosphorylation in the C-terminal domain mediated by TBK1 and/or IKKi, requiring Ser386 and/or Ser385- site 1; and a cluster of serine/threonine residues between Ser396 and Ser405- site 2 [Panne et al 2007]. Phosphorylated residues at site 2 (Ser396 - Ser405) alleviate autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitate phosphorylation at site 1 (Ser385 or Ser386). Phosphorylation at site 1 is required for IRF3 dimerization.

Literature References
PubMed ID Title Journal Year
12692549 IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway

Coyle, AJ, Faia, KL, Fitzgerald, KA, Liao, SM, Rowe, DC, Latz, E, McWhirter, SM, Golenbock, DT, Maniatis, T

Nat Immunol 2003
17526488 Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch

McWhirter, SM, Maniatis, T, Harrison, SC, Panne, D

J Biol Chem 2007
9463386 Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300

Nishida, E, Fukuda, M, Suhara, W, Fujita, T, Fukuhara, Y, Yoneyama, M

EMBO J 1998
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
NLRP4:DTX4:dsDNA:ZBP1:pS-172-TBK1 [cytosol] (Homo sapiens)
Authored
Shamovsky, V  (2011-09-21)
Reviewed
Mocarski, ES  (2012-02-19)
Upton, JW  (2012-02-19)
D'Eustachio, P  (2011-12-07)
Created
Shamovsky, V  (2011-09-21)
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