TY - JOUR
T1 - Glycogen Synthase Kinase 3β Regulates IRF3 Transcription Factor-Mediated Antiviral Response via Activation of the Kinase TBK1
AU - Lei, Cao Qi
AU - Zhong, Bo
AU - Zhang, Yu
AU - Zhang, Jing
AU - Wang, Shuai
AU - Shu, Hong Bing
N1 - Funding Information:
We thank J. Woodgett, J. Hiscott, R. Lin, K. Fitzgerald, and Z. Huang for reagents and W.-W. Luo, R. Chen, and Y. Ran for technique assistance. This work was supported by grants from the Chinese 973 program (#2006CB504301 and #2010CB911802), the National Natural Science Foundation of China (#30630019 and #30921001), and the Chinese Science and Technology Key Project (2008ZX10002-014).
PY - 2010/12/14
Y1 - 2010/12/14
N2 - Viral infection activates transcription factors IRF3 and NF-κB, which collaborate to induce type I interferons (IFNs). Here, we identified glycogen synthase kinase 3β (GSK3β) as an important regulator for virus-triggered IRF3 and NF-κB activation, IFN-β induction, and cellular antiviral response. Overexpression of GSK3β potentiated virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas reduced expression or deletion of GSK3β impaired virus-induced IRF3 and NF-κB activation, transcription of the IFNB1 gene, as well as cellular antiviral response. GSK3β physically associated with the kinase TBK1 in a viral infection-dependent manner. GSK3β promoted TBK1 self-association and autophosphorylation at Ser172, which is critical for virus-induced IRF3 activation and IFN-β induction. The effect of GSK3β on virus-induced signaling is independent of its kinase activity. Our findings suggest that GSK3β plays important roles in virus-triggered IRF3 activation by promoting TBK1 activation and provide new insights to the molecular mechanisms of cellular antiviral response.
AB - Viral infection activates transcription factors IRF3 and NF-κB, which collaborate to induce type I interferons (IFNs). Here, we identified glycogen synthase kinase 3β (GSK3β) as an important regulator for virus-triggered IRF3 and NF-κB activation, IFN-β induction, and cellular antiviral response. Overexpression of GSK3β potentiated virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas reduced expression or deletion of GSK3β impaired virus-induced IRF3 and NF-κB activation, transcription of the IFNB1 gene, as well as cellular antiviral response. GSK3β physically associated with the kinase TBK1 in a viral infection-dependent manner. GSK3β promoted TBK1 self-association and autophosphorylation at Ser172, which is critical for virus-induced IRF3 activation and IFN-β induction. The effect of GSK3β on virus-induced signaling is independent of its kinase activity. Our findings suggest that GSK3β plays important roles in virus-triggered IRF3 activation by promoting TBK1 activation and provide new insights to the molecular mechanisms of cellular antiviral response.
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U2 - 10.1016/j.immuni.2010.11.021
DO - 10.1016/j.immuni.2010.11.021
M3 - Article
C2 - 21145761
AN - SCOPUS:78650177936
SN - 1074-7613
VL - 33
SP - 878
EP - 889
JO - Immunity
JF - Immunity
IS - 6
ER -