The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways.
Intracellular detection of RNA virus infection is mediated by the RNA helicase RIG-I, which is recruited to mitochondria by the adaptor protein MAVS and triggers activation of the transcription factors NF-kappaB, IRF3 and IRF7. Here we demonstrate that virus-induced activation of IRF3 and IRF7 depended on the NF-kappaB modulator NEMO, ... which acted 'upstream' of the kinases TBK1 and IKKepsilon. IRF3 phosphorylation, formation of IRF3 dimers and DNA binding, as well as IRF3-dependent gene expression, were abrogated in NEMO-deficient cells. IRF3 phosphorylation and interferon production were restored by ectopic expression of NEMO. Thus, NEMO, like MAVS, acts as an adaptor protein that allows RIG-I to activate both the NF-kappaB and IRF signaling pathways.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Line, DEAD-box RNA Helicases, Humans, I-kappa B Kinase, Interferon Regulatory Factors, Interferons, Intracellular Signaling Peptides and Proteins, Mice, Mice, Knockout, NF-kappa B, Promoter Regions, Genetic, Protein Binding, Protein-Serine-Threonine Kinases, RNA Viruses, Signal Transduction, Virus Replication
Adaptor Proteins, Signal Transducing, Animals, Cell Line, DEAD-box RNA Helicases, Humans, I-kappa B Kinase, Interferon Regulatory Factors, Interferons, Intracellular Signaling Peptides and Proteins, Mice, Mice, Knockout, NF-kappa B, Promoter Regions, Genetic, Protein Binding, Protein-Serine-Threonine Kinases, RNA Viruses, Signal Transduction, Virus Replication
Nat. Immunol.
Date: Jun. 01, 2007
PubMed ID: 17468758
View in: Pubmed Google Scholar
Download Curated Data For This Publication
137938
Switch View:
- Interactions 3