TBK1-like transcript negatively regulates the production of IFN and IFN-stimulated genes through RLRs-MAVS-TBK1 pathway
TBK1-like transcript negatively regulates the production of IFN and IFN-stimulated genes through RLRs-MAVS-TBK1 pathway
复制标题
TBK1样转录本通过RLRs-MAVS-TBK1途径负向调节IFN和IFN刺激基因的产生
DOI：
10.1016/j.fsi.2016.04.002
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发表时间：
2016
影响因子：
4.7
通讯作者：
Chang Ming Xian
中科院分区：
文献类型：
--
作者：
Zhang Lin;Chen Wen Qin;Hu Yi Wei;Wu Xiao Man;Nie P.;Chang Ming Xian
TANK结合激酶1（TBK 1）是Toll样受体（TLR）和视黄酸诱导基因I（RIG-I）介导的I型IFN诱导和宿主抗病毒防御所必需的丝氨酸/苏氨酸蛋白激酶。本研究从斑马鱼中克隆了TBK 1-like转录本TBK 1 L。与TBK 1相比，TBK 1 L含有一个不完整的S_TKc结构域，缺乏UBL_TBK1_like结构域。RT-PCR结果显示，TBK 1 L在胚胎、早期幼虫和ZF 4细胞中组成型表达，而在ZF 4细胞中SVCV感染后无表达。TBK 1而非TBK 1 L的过表达导致斑马鱼IFN 1和IFN 3启动子的显著激活。同样，TBK 1 L对细胞的抗病毒状态几乎没有影响。然而，TBK 1 L的过表达负调控由视黄酸诱导基因I样受体（RLRs）、MAVS和TBK 1介导的斑马鱼IFN 1和/或IFN 3启动子的诱导。此外，TBK 1 L在斑马鱼胚胎中的过表达导致TBK 1诱导的许多IFN刺激基因的产生减少。总的来说，这些数据支持斑马鱼TBK 1 L负调控RLRs-MAVS-TBK 1通路。
TANK-binding kinase 1 (TBK1) is an essential serine/threonine-protein kinase required for Toll-like receptor (TLR)- and retinoic acid-inducible gene I (RIG-I) -mediated induction of type I IFN and host antiviral defense. In the present study, TBK1-like transcript, namely TBK1L, was cloned from zebrafish. Compared with TBK1, TBK1L contains an incomplete S_TKc domain, and lacks UBL_TBK1_like domain. Realtime PCR showed that TBK1L was constitutively produced in embryos, early larvae and ZF4 cells, and unchanged in ZF4 cells following SVCV infection. Overexpression of TBK1 but not TBK1L resulted in significant activation of zebrafish IFN1 and IFN3 promoters. Similarly, TBK1L had little impact on the antiviral state of the cells. However, the overexpression of TBK1L negatively regulated the induction of zebrafish IFN1 and/or IFN3 promoters mediated by the retinoic acid-inducible gene I-like receptors (RLRs), MAVS and TBK1. In addition, the overexpression of TBK1L in zebrafish embryos led to the decreased production of many IFN-stimulated genes induced by TBK1. Collectively, these data support that zebrafish TBK1L negatively regulates RLRs-MAVS-TBK1 pathway.