RNF144B inhibits LPS-induced inflammatory responses via binding TBK1
RNF144B inhibits LPS-induced inflammatory responses via binding TBK1
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RNF144B 通过结合 TBK1 抑制 LPS 诱导的炎症反应
DOI：
10.1002/jlb.2a0819-055r
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发表时间：
2019-09-11
影响因子：
5.5
通讯作者：
Li, Xia
中科院分区：
文献类型：
--
作者：
Zhang, Zhen;Zhang, Luoyan;Li, Xia
需要精确控制先天免疫反应，以避免长期炎症，防止对宿主造成不必要的损害。在这里，我们报告了RNF144B对内毒素刺激的动态反应和对内毒素诱导的炎症的负调控。我们发现，RNF144B通过插入环(IBR)结构域与坦克结合蛋白1(TBK1)的支架/二聚结构域(SDD)相互作用，抑制其磷酸化和K63连接的多泛素化，从而导致TBK1失活、IRF3去磷酸化和干扰素-β减少。用siRNA敲除RNF144B可增加脂多糖刺激后IRF3的激活和干扰素-β的产生。我们的研究发现，RNF144B与TBK1的相互作用足以使TBK1失活，并揭示了RNF144B在先天性免疫反应中的一个先前未被认识的角色。
Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS-induced inflammation. We found that RNF144B interacted with the scaffold/dimerization domain (SDD) of TANK binding kinase 1 (TBK1) through the in between RING (IBR) domain to inhibit its phosphorylation and K63-linked polyubiquitination, which led to TBK1 inactivation, IRF3 dephosphorylation, and IFN-beta reduction. RNF144B knockdown with siRNA increased IRF3 activation and IFN-beta production in response to LPS stimulation. Our study identifies that RNF144B interaction with TBK1 is sufficient to inactivate TBK1 and delineates a previously unrecognized role for RNF144B in innate immune responses.