Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
FEBS Lett. 2010 Mar 5;584(5):865-72. doi: 10.1016/j.febslet.2010.01.060. Epub 2010 Feb 5.
Epstein-Barr virus latent membrane protein 1 (LMP1) activates NF-kappaB signaling pathways through two C-terminal regions, CTAR1 and CTAR2. Previous studies have demonstrated that BS69, a multidomain cellular protein, regulates LMP1/CTAR2-mediated NF-kappaB activation by interfering with the complex formation between TRADD and LMP1/CTAR2. Here, we found that BS69 directly interacted with the LMP1/CTAR1 domain and regulated LMP1/CTAR1-mediated NF-kappaB activation and subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69 directly interacted with TRAF3, a negative regulator of NF-kappaB activation. Furthermore, small-interfering RNA-mediated knockdown experiments revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-kappaB activation.
Epstein-Barr 病毒潜伏膜蛋白 1（LMP1）通过两个 C 端区域 CTAR1 和 CTAR2 激活 NF-κB 信号通路。先前的研究表明，多结构域细胞蛋白 BS69 通过干扰 TRADD 和 LMP1/CTAR2 之间的复合物形成来调节 LMP1/CTAR2 介导的 NF-κB 激活。在这里，我们发现 BS69 与 LMP1/CTAR1 结构域直接相互作用，并调节 LMP1/CTAR1 介导的 NF-κB 激活和随后的 IL-6 产生。关于涉及的机制，我们发现 BS69 直接与 TRAF3 相互作用，TRAF3 是 NF-κB 激活的负调节剂。此外，小干扰 RNA 介导的敲低实验表明，TRAF3 参与了 BS69 介导的抑制 LMP1/CTAR1 诱导的 NF-κB 激活。
