Death-associated protein kinase 1 is an IRF3/7-interacting protein that is involved in the cellular antiviral immune response
Death-associated protein kinase 1 is an IRF3/7-interacting protein that is involved in the cellular antiviral immune response
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DOI：
10.1038/cmi.2013.65
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发表时间：
2014-02
影响因子：
24.1
通讯作者：
Jing Zhang;Ming-Ming Hu-Ming;H. Shu;Shu Li
中科院分区：
文献类型：
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作者：
Jing Zhang;Ming-Ming Hu-Ming;H. Shu;Shu Li
干扰素调节因子7（Interferon Regulatory Factor，IRF）是病毒介导的I型干扰素（Interferon，IFN）产生的主要调节因子，在机体抗病毒的先天性免疫应答中发挥重要作用。在这里，我们确定死亡相关蛋白激酶1（DAPK 1）作为IRF 7相互作用的蛋白串联亲和纯化（TAP）。病毒感染诱导DAPK 1-IRF 7和DAPK 1-IRF 3相互作用，并且DAPK 1的过表达增强了病毒诱导的干扰素刺激反应元件（ISRE）和IFN-β启动子的激活以及IFN-β 1基因的表达。DAPK 1的敲低减弱了由病毒感染或IFN-β触发的IFNB 1和RIG-I表达的诱导，并且它们被病毒复制增强。此外，病毒感染或IFN-β处理诱导DAPK 1的表达。IFN-β处理还通过降低其丝氨酸308处的磷酸化水平来激活DAPK 1。有趣的是，DAPK 1参与病毒诱导的信号转导与其激酶活性无关。因此，我们的研究确定DAPK 1是细胞抗病毒反应的重要调节因子。
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.