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[摘要]：Recognition of viral RNA by cytoplasmic retinoic acid inducible gene I (RIG-I)-like receptors initiates signals leading to the induction of type I interferon (IFN) transcription via transcription factors such as interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kappa B). Here, we describe a new signalling pathway that involves protein kinase C alpha (PKC alpha), histone deacetylase 6 (HDAC6) and beta-catenin (beta-catenin), which is essential for IFN gene induction following virus infection. Knockdown of PKC alpha in various human cells, including primary cells, inhibited Sendai virus (SeV)-mediated IFN induction and enhanced virus replication. In the absence of this pathway IRF3 becomes activated, but does not bind to its promoter and is thus unable to support transcription. Mechanistically, SeV infection induced the activation of PKC alpha, which promoted its interaction with HDAC6 and enhanced its deacetylation activity in a phosphorylation-dependent manner. Further downstream, HDAC6 caused deacetylation of beta-catenin and enhanced its nuclear translocation and promoter binding. In the nucleus, beta-catenin acted as a co-activator for IRF3-mediated transcription. Our findings suggest an important role of a novel signalling pathway mediated by PKC alpha-HDAC6-beta-catenin in controlling IRF3-mediated transcription. The EMBO Journal (2011) 30, 4838-4849. doi:10.1038/emboj.2011.351; Published online 27 September 2011 |
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