Kaye K M, Devergne O, Harada J N, Izumi K M, Yalamanchili R, Kieff E, Mosialos G
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11085-90. doi: 10.1073/pnas.93.20.11085.
Latent infection membrane protein 1 (LMP1), the Epstein-Barr virus transforming protein, associates with tumor necrosis factor receptor (TNFR) associated factor 1 (TRAF1) and TRAF3. Since TRAF2 has been implicated in TNFR-mediated NF-kappa B activation, we have evaluated the role of TRAF2 in LMP1-mediated NF-kappa B activation. TRAF2 binds in vitro to the LMP1 carboxyl-terminal cytoplasmic domain (CT), coprecipitates with LMP1 in B lymphoblasts, and relocalizes to LMP1 plasma membrane patches. A dominant negative TRAF2 deletion mutant that lacks amino acids 6-86 (TRAF/ delta 6-86) inhibits NF-kappa B activation from the LMP1 CT and competes with TRAF2 for LMP1 binding. TRAF2 delta 6-86 inhibits NF-kappa B activation mediated by the first 45 amino acids of the LMP1 CT by more than 75% but inhibits NF-kappa B activation through the last 55 amino acids of the CT by less than 40%. A TRAF interacting protein, TANK, inhibits NF-kappa B activation by more than 70% from both LMP1 CT domains. These data implicate TRAF2 aggregation in NF-kappa B activation by the first 45 amino acids of the LMP1 CT and suggest that a different TRAF-related pathway may be involved in NF-kappa B activation by the last 55 amino acids of the LMP1 CT.
潜伏感染膜蛋白1（LMP1）是一种爱泼斯坦-巴尔病毒转化蛋白，它与肿瘤坏死因子受体（TNFR）相关因子1（TRAF1）和TRAF3相互作用。由于TRAF2与TNFR介导的核因子κB（NF-κB）激活有关，我们评估了TRAF2在LMP1介导的NF-κB激活中的作用。TRAF2在体外与LMP1的羧基末端胞质结构域（CT）结合，在B淋巴母细胞中与LMP1共沉淀，并重新定位于LMP1质膜斑块。一种缺失氨基酸6 - 86的显性负性TRAF2缺失突变体（TRAF/δ6 - 86）抑制了LMP1 CT诱导的NF-κB激活，并与TRAF2竞争LMP1结合。TRAF2δ6 - 86抑制LMP1 CT前45个氨基酸介导的NF-κB激活超过75%，但通过CT的最后55个氨基酸抑制NF-κB激活不到40%。一种TRAF相互作用蛋白TANK，可抑制LMP1两个CT结构域诱导的NF-κB激活超过70%。这些数据表明TRAF2聚集参与LMP1 CT前45个氨基酸诱导的NF-κB激活，并提示可能存在不同的TRAF相关途径参与LMP1 CT最后55个氨基酸诱导的NF-κB激活。
