Article abstract
Nature Immunology 8, 592 - 600 (2007)
Published online: 29 April 2007 | doi:10.1038/ni1465
The NEMO adaptor bridges the nuclear factor-
B and interferon regulatory factor signaling pathways
Tiejun Zhao1, Long Yang1,3, Qiang Sun1, Meztli Arguello1,2, Dean W Ballard4, John Hiscott1,2,3 & Rongtuan Lin1,3
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-
B, IRF3 and IRF7. Here we demonstrate that virus-induced activation of IRF3 and IRF7 depended on the NF-B modulator NEMO, which acted 'upstream' of the kinases TBK1 and IKK
. 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-B and IRF signaling pathways.
- Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal H3T 1E2, Canada.
- Department of Microbiology & Immunology, McGill University, Montreal H3T 1E2, Canada.
- Department of Medicine, McGill University, Montreal H3T 1E2, Canada.
- Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Correspondence to: Rongtuan Lin1,3 e-mail: rongtuan.lin@mcgill.ca
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