Reactome | IRF3 mediated activation of type 1 IFN

IRF3 mediated activation of type 1 IFN

Stable Identifier

R-HSA-1606341

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Interferon regulatory factors (IRF) IRF-3 and IRF-7 are the major modulators of IFN gene expression in response to pathogenic molecules. The relative contribution of IRF3 and IRF7 depends on the signaling pathway that is activated. Type I IFN production in cytosolic DNA-sensing pathway is mediated predominantly by IRF3 and partially by IRF7, since DNA-stimulated IFN-beta and IFN-alpha4 mRNA induction was strongly inhibited in IRF3-deficient mouse embryonic fibroblasts (MEFs), while remained normal (IFN-beta) or reduced (IFN-alpha4) in IRF7-deficient MEFs (Takaoke A et al 2007). IRF3 activation in response to B-DNA stimulation occurs via its co-recruitment with serine/threonine kinase TANK-binding kinase 1 (TBK1) or inducible IkB kinase (IKKi/IKKepsilon) to the C-terminal region of DAI.

Literature References

PubMed ID	Title	Journal	Year
18375758	Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules Wang, Z, Choi, MK, Ban, T, Yanai, H, Negishi, H, Tamura, T, Takaoka, A, Nishikura, K, Taniguchi, T, Lu, Y	Proc Natl Acad Sci U S A	2008
16413926	Recognition of cytosolic DNA activates an IRF3-dependent innate immune response Stetson, DB, Medzhitov, R	Immunity	2006
17618271	DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response Takaoka, A, Wang, Z, Choi, MK, Yanai, H, Negishi, H, Lu, Y, Ban, T, Miyagishi, M, Kodama, T, Honda, K, Ohba, Y, Taniguchi, T	Nature	2007
19846511	Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1 DeFilippis, VR, Alvarado, D, Sali, T, Rothenburg, S, Früh, K	J Virol	2010