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| Subject Categories: Signal Transduction | Immunology |
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| The EMBO Journal
(2005) 24, 4018–4028, doi:10.1038/sj.emboj.7600863 Published online 10 November 2005 |
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SIKE is an IKK /TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways |
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| Jun Huang1, 4, Ting Liu1, 4, Liang-Guo Xu2, Danying Chen1, Zhonghe Zhai1 and Hong-Bing Shu1, 3 |
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1 College of Life Sciences, Peking University, Beijing, China 2 National Jewish Medical and Research Center, Denver, CO, USA 3 College of Life Sciences, Wuhan University, Wuhan, China To whom correspondence should be addressed Hong-Bing Shu, College of Life Sciences, Wuhan University, Wuhan 430072, China. Tel.: +86 27 6875 3780; Fax: +86 27 6875 3780; E-mail: shuh@whu.edu.cn 4 These are co-first authors Received 29 August 2005; Accepted 11 October 2005; Published online 10 November 2005. |
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| Abstract |
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Viral infection or TLR3 engagement causes activation of the transcription factors IRF-3 and NF- B, which collaborate to induce transcription of type I IFN genes. IKK and TBK1 are two IKK-related kinases critically involved in virus- and TLR3-triggered activation of IRF-3. We identified a protein termed SIKE (for Suppressor of IKK) that interacts with IKK and TBK1. SIKE is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation. Overexpression of SIKE disrupted the interactions of IKK or TBK1 with TRIF, RIG-I and IRF-3, components in virus- and TLR3-triggered IRF-3 activation pathways, but did not disrupt the interactions of TRIF with TRAF6 and RIP, components in TLR3-triggered NF-B activation pathway. Consistently, overexpression of SIKE inhibited virus- and TLR3-triggered interferon-stimulated response elements (ISRE) but not NF-B activation. Knockdown of SIKE potentiated virus- and TLR3-triggered ISRE but not NF-B activation. Moreover, overexpression of SIKE inhibited IKK- and TBK1-mediated antiviral response. These findings suggest that SIKE is a physiological suppressor of IKK and TBK1 and plays an inhibitory role in virus- and TLR3-triggered IRF-3 but not NF-B activation pathways. |
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| Keywords: antiviral response, IKK, IRF-3, NF-B, TBK1 |
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