ZBP1(DAI) mediated induction of type I IFNs

Stable Identifier
R-HSA-1606322
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Pathway
Species
Homo sapiens
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Z-DNA-binding protein-1 (ZBP1), also known as, DNA-dependent activator of IFN-regulatory factors (DAI) was reported to initiate innate immune responses in murine L929 cells upon stimulation by multiple types of exogenously added DNA (Takaoka A et al 2007). Human cytomegalovirus (HCMV) was shown to stimulate ZBP1-mediated induction of IRF3 in human foreskin (DeFilippis VR et al 2010). ZBP1 was also implicated in activation of NF-kappaB pathways in human embryonic kidney HEK293T cells (Kaiser WJ et al 2008, Rebsamen M et al 2009). However, the role and importance ofZBP1 as dsDNA sensor remain controversial, since knocking down ZBP1 expression in other human or murine cell types by siRNA had very little effect on cellular responses to cytosolic DNA, suggesting the presence of alternative pathway (Wang ZC et al 2008, Lippmann J et al 2008). Tissue-specific expression of human ZBP1 also suggests that ZBP1 may function in cell-type specific way (Rothenburg S et al 2002).

Literature References
PubMed ID Title Journal Year
18941233 Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors

Kaiser, WJ, Upton, JW, Mocarski, ES

J Immunol 2008
11842111 Complex regulation of the human gene for the Z-DNA binding protein DLM-1

Rothenburg, S, Schwartz, T, Koch-Nolte, F, Haag, F

Nucleic Acids Res 2002
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
19590578 DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB

Rebsamen, M, Heinz, LX, Meylan, E, Michallet, MC, Schroder, K, Hofmann, K, Vazquez, J, Benedict, CA, Tschopp, J

EMBO Rep 2009
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
18771559 IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI)

Lippmann, J, Rothenburg, S, Deigendesch, N, Eitel, J, Meixenberger, K, van Laak, V, Slevogt, H, N'guessan, PD, Hippenstiel, S, Chakraborty, T, Flieger, A, Suttorp, N, Opitz, B

Cell Microbiol 2008
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
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