title: Death-associated protein kinase 1 is an IRF3/7-interacting protein that is involved in the cellular antiviral immune response.
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.
authors: Jing
authors: J
authors: Zhang
authors: Ming-Ming
authors: MM
authors: Hu
authors: Hong-Bing
authors: HB
authors: Shu
authors: Shu
authors: S
authors: Li
mesh_terms: D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism*; D016899:Interferon-beta / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction; D014780:Viruses / Q000187:drug effects / Q000276:immunology*
chemical_list: C494232:IRF3 protein, human; C494234:IRF7 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases