The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways - PubMed (original) (raw)

doi: 10.1038/ni1465. Epub 2007 Apr 29.

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

Tiejun Zhao et al. Nat Immunol. 2007 Jun.

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.

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