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.
Zhao
Tiejun
T
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal H3T 1E2, Canada.
Yang
Long
L
Sun
Qiang
Q
Arguello
Meztli
M
Ballard
Dean W
DW
Hiscott
John
J
Lin
Rongtuan
R
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012328:RNA Viruses / Q000502:physiology; D015398:Signal Transduction; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; C491731:IKBKG protein, human; D050835:Interferon Regulatory Factors; D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; D016328:NF-kappa B; C484406:TANK protein, human; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases