irf3 dna

Cgas recognizes bacterial viral dna and is a strong activator of sting that can further activate irf3 and subsequent type i interferon production. However how sting activates irf3 is unclear. The cgas sting pathway is important for immune defense against infection and cancer.
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Irf3 was originally discovered as a homolog of irf1 and irf2 irf3 has been further characterized and shown to contain several functional domains including a nuclear export signal a dna binding domain a c terminal irf association domain and several regulatory phosphorylation sites. Cgamp then acts a second messenger binding to sting to trigger activation of the transcription factor irf3. Dna is a pathogen associated molecular pattern when it is delivered to the host cytoplasm by microbial infection and is a danger associated molecular pattern when enters the cytoplasm from the.

Irf3 leads to transcription of type 1 ifn β.

Irf3 dna. Review in the present study the authors found that herpes simplex virus 1 tegument protein ul41 was involved in counteracting the cgas sting mediated dna sensing pathway. Mtp53 interferes with the function of the cytoplasmic dna sensing machinery cgas sting tbk1 irf3 that activates the innate immune response. Cgas is unable to produce 2 3 cgamp in the presence of rna. Cytosolic double stranded dna dsdna stimulates the production of type i interferon ifn through the endoplasmic reticulum er resident adaptor protein sting stimulator of ifn genes which activates the transcription factor interferon regulatory factor 3 irf3.

Map3k8 mediates the phosphorylation and repression of irf3 homodimers to promote greater transcriptional activity through utilization of irf3 irf7 heterodimers. Data are the mean sd of three experiments. Article cas pubmed pubmed central google scholar. Upon directly binding cytosolic dna cgas forms dimers to catalyze production of 2 3 cgamp from atp and gtp.

Recognition of cytosolic dna activates an irf3 dependent innate immune response. Sting activation triggers multiple signaling cascades leading to activation of irf3 nf κb and autophagy. Irf3 is a member of the interferon regulatory transcription factor irf family. Immunity 24 93 103 2006.

Data indicate that knockdown of irf 7 expression almost completely diminished the enhancing effect of tlr9 signaling on foxp3 expression suggesting that irf 7 is a downstream molecule. By generating mice harboring mutations of sting that specifically inactivate different signaling cascades we found that ablation of irf3 activation which is essential for the induction of type i. H and i elisa analysis of 2 3 cgamp production and quantification of immunoblot analysis of irf3 phosphorylation in mcf10a cgas cells reconstituted with hcgas or hcgas phase separation mutant alleles and transfected with plasmid dna. Mtp53 but not wild type p53 binds to tank binding protein kinase 1 tbk1 and prevents the formation of a trimeric complex between tbk1 sting and irf3 which is required for activation nuclear.