Zhao Tiejun, Yang Long, Sun Qiang, Arguello Meztli, Ballard Dean W, Hiscott John, Lin Rongtuan
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal H3T 1E2, Canada.
Nat Immunol. 2007 Jun;8(6):592-600. doi: 10.1038/ni1465. Epub 2007 Apr 29.
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.
RNA病毒感染的细胞内检测由RNA解旋酶RIG-I介导，RIG-I通过衔接蛋白MAVS被招募到线粒体，并触发转录因子NF-κB、IRF3和IRF7的激活。在此我们证明，病毒诱导的IRF3和IRF7激活依赖于NF-κB调节剂NEMO，其作用于激酶TBK1和IKKε的“上游”。在NEMO缺陷细胞中，IRF3磷酸化、IRF3二聚体形成和DNA结合以及IRF3依赖性基因表达均被废除。通过NEMO的异位表达可恢复IRF3磷酸化和干扰素产生。因此，NEMO与MAVS一样，作为一种衔接蛋白，使RIG-I能够激活NF-κB和IRF信号通路。
