The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways.

Abstract

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.

• Authors: Tiejun Zhao, Long Yang, Qiang Sun, Meztli Arguello, Dean W Ballard, John Hiscott, Rongtuan Lin
• Journal: Nature immunology (Nat Immunol) Vol. 8 Issue 6 Pg. 592-600 (Jun 2007) ISSN: 1529-2908 [Print] United States
• PMID: 17468758 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• IKBKG protein, human
• Interferon Regulatory Factors
• Intracellular Signaling Peptides and Proteins
• NEMO protein, mouse
• NF-kappa B
• TANK protein, human
• Interferons
• Protein Serine-Threonine Kinases
• TBK1 protein, human
• I-kappa B Kinase
• Ddx58 protein, mouse
• DEAD Box Protein 58
• DEAD-box RNA Helicases

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Animals
• Cell Line
• DEAD Box Protein 58
• DEAD-box RNA Helicases (metabolism)
• Humans
• I-kappa B Kinase (genetics, metabolism)
• Interferon Regulatory Factors (metabolism)
• Interferons (biosynthesis, genetics)
• Intracellular Signaling Peptides and Proteins (deficiency, genetics, metabolism)
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• Promoter Regions, Genetic
• Protein Binding
• Protein Serine-Threonine Kinases (metabolism)
• RNA Viruses (physiology)
• Signal Transduction
• Virus Replication