Helicobacter pylori CagA activates NF-κB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination
Helicobacter pylori CagA activates NF-κB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination
复制标题
DOI：
10.1038/embor.2009.210
复制
发表时间：
2009-11-01
期刊：
影响因子：
7.7
通讯作者：
Chen, Lin-Feng
中科院分区：
文献类型：
--
作者：
Lamb, Acacia;Yang, Xiao-Dong;Chen, Lin-Feng
幽门螺杆菌引发的慢性胃炎的特点是促炎细胞因子的cag致病岛依赖性上调，这主要是由转录因子核因子（NF）-κB介导的。然而，参与幽门螺杆菌诱导的NF-κB激活和炎症反应的cag致病岛编码蛋白和细胞信号分子仍不清楚。在这里，我们发现幽门螺杆菌毒力因子 CagA 和宿主蛋白转化生长因子-β 激活激酶 1 (TAK1) 对于幽门螺杆菌诱导的 NF-κ B 激活至关重要。CagA 与 TAK1 物理结合，并通过肿瘤坏死因子受体相关因子 6 介导的 Lys 63 连接泛素化增强其活性和 TAK1 诱导的 NF-κ B 激活。 TAK1。这些发现表明，TAK1 的多泛素化调节 NF-κ B 的激活，而 NF-κ B 反过来又被幽门螺杆菌 CagA 用于幽门螺杆菌诱导的炎症反应。
Helicobacter pylori-initiated chronic gastritis is characterized by the cag pathogenicity island-dependent upregulation of proinflammatory cytokines, which is largely mediated by the transcription factor nuclear factor (NF)-kappa B. However, the cag pathogenicity island-encoded proteins and cellular signalling molecules that are involved in H. pylori-induced NF-kappa B activation and inflammatory response remain unclear. Here, we show that H. pylori virulence factor CagA and host protein transforming growth factor-beta-activated kinase 1 (TAK1) are essential for H. pylori-induced activation of NF-kappa B. CagA physically associates with TAK1 and enhances its activity and TAK1-induced NF-kappa B activation through the tumour necrosis factor receptor-associated factor 6-mediated, Lys 63-linked ubiquitination of TAK1. These findings show that polyubiquitination of TAK1 regulates the activation of NF-kappa B, which in turn is used by H. pylori CagA for the H. pylori-induced inflammatory response.