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Death-associated protein kinase 1 is an IRF3/7-interacting protein that is involved in the cellular antiviral immune response

Cellular & Molecular Immunology volume 11, pages 245–252 (2014)Cite this article

Abstract

Interferon regulatory factor (IRF) 7 has been demonstrated to be a master regulator of virus-induced type I interferon production (IFN), and it plays a central role in the innate immune response against viruses. Here, we identified death-associated protein kinase 1 (DAPK1) as an IRF7-interacting protein by tandem affinity purification (TAP). Viral infection induced DAPK1–IRF7 and DAPK1–IRF3 interactions and overexpression of DAPK1 enhanced virus-induced activation of the interferon-stimulated response element (ISRE) and IFN-β promoters and the expression of the IFNB1 gene. Knockdown of DAPK1 attenuated the induction of IFNB1 and RIG-I expression triggered by viral infection or IFN-β, and they were enhanced by viral replication. In addition, viral infection or IFN-β treatment induced the expression of DAPK1. IFN-β treatment also activated DAPK1 by decreasing its phosphorylation level at serine 308. Interestingly, the involvement of DAPK1 in virus-induced signaling was independent of its kinase activity. Therefore, our study identified DAPK1 as an important regulator of the cellular antiviral response.

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Acknowledgements

We thank the members of our laboratory for their technical help and stimulating discussions. This work was supported by grants from the Ministry of Science and Technology of China (2012CB910201, 2010CB911802) and the National Natural Science Foundation of China (31221061, 31130020, 31101019 and 91029302).

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  1. College of Life Sciences, Wuhan University, Wuhan, China

    Jing Zhang, Ming-Ming Hu, Hong-Bing Shu & Shu Li

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Correspondence to Shu Li.

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Zhang, J., Hu, MM., Shu, HB. et al. Death-associated protein kinase 1 is an IRF3/7-interacting protein that is involved in the cellular antiviral immune response. Cell Mol Immunol 11, 245–252 (2014). https://doi.org/10.1038/cmi.2013.65

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