Glycogen synthase kinase 3beta regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1.
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Lei CQ, Zhong B, Zhang Y, Zhang J, Wang S, Shu HB
Glycogen synthase kinase 3beta regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1.
Immunity. 2010 Dec 14;33(6):878-89. doi: 10.1016/j.immuni.2010.11.021. Epub 2010 Dec 9.
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- 21145761 [ View in PubMed]
- Abstract
Viral infection activates transcription factors IRF3 and NF-kappaB, which collaborate to induce type I interferons (IFNs). Here, we identified glycogen synthase kinase 3beta (GSK3beta) as an important regulator for virus-triggered IRF3 and NF-kappaB activation, IFN-beta induction, and cellular antiviral response. Overexpression of GSK3beta potentiated virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas reduced expression or deletion of GSK3beta impaired virus-induced IRF3 and NF-kappaB activation, transcription of the IFNB1 gene, as well as cellular antiviral response. GSK3beta physically associated with the kinase TBK1 in a viral infection-dependent manner. GSK3beta promoted TBK1 self-association and autophosphorylation at Ser172, which is critical for virus-induced IRF3 activation and IFN-beta induction. The effect of GSK3beta on virus-induced signaling is independent of its kinase activity. Our findings suggest that GSK3beta plays important roles in virus-triggered IRF3 activation by promoting TBK1 activation and provide new insights to the molecular mechanisms of cellular antiviral response.