Epstein-Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF-kappa B activation
Epstein-Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF-kappa B activation
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DOI：
10.1038/sj.onc.1201359
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发表时间：
1997-10-09
期刊：
影响因子：
8
通讯作者：
Rowe, M
中科院分区：
文献类型：
--
作者：
Floettmann, JE;Rowe, M
Epstein-Barr病毒潜伏膜蛋白-1(LMP1)具有与其结构特征和功能一致的细胞表面活性受体。已知的LMP1与TRAF家族成员的联系表明，LMP1传递的信号类似于肿瘤坏死因子受体(TNFR)家族的细胞表面受体，后者通过形成二聚体或三聚体来响应细胞外配体的结合而发出信号。然而，到目前为止，LMP1与TRAF之间的相互作用仅在LMP1的C末端活化区1(CTAR1)上被描述，而TRAF与第二个核因子-kappaB激活域(CTAR2)之间的直接相互作用尚未见报道。我们现在已经将CTAR2的NF-kappa B激活结构域定位到远C末端(B95.8 LMP1的密码子379到384)的一个高度保守的6个氨基酸的延伸部分。此外，我们还构建了包含大鼠CD2胞外区和跨膜区的嵌合受体分子，并将其与编码CTAR1和/或CTAR2结构域的LMP1的C末端融合。有趣的是，单独编码CTAR2的嵌合体的功能以及同时编码CTAR1和CTAR2的嵌合体的功能被发现在抗体介导的交联剂中是可诱导的。这些可诱导的嵌合蛋白也使我们能够证明LMP1介导的NF-kappa B激活是LMP1激活后的即时事件。
The Epstein-Barr virus Latent Membrane Protein-1 (LMP1) has structural features and functions consistent with it being a constitutively active cell surface receptor. The known association of LMP1 with members of the TRAF family of proteins suggests that LMP1 transduces signals similarly to the Tumour Necrosis Factor Receptor (TNFR) family of cell surface receptors that signal by forming dimers or trimers in response to binding of extracellular ligands. However, interactions between LMP1 and the TRAFs have so far only been described for the C-terminal activation region 1 (CTAR1) of LMP1 and no direct interactions of the TRAFs with the second NF-kappa B activation domain (CTAR2) have been reported. We have now mapped the NF-kappa B activation domain of CTAR2 to a highly conserved stretch of 6 amino acids at the far C-terminus (codons 379 to 384 in B95.8 LMP1). In addition, we constructed chimeric receptor molecules which contain the ligand-binding extracellular domain and the transmembrane domain of rat CD2 fused to the C-terminus of LMP1 encoding the CTAR1 and/or the CTAR2 domain. Interestingly, the function of a chimera encoding CTAR2 alone, as well as the function of a chimera encoding both CTAR1 and CTAR2 was found to be inducible upon antibody-mediated crosslinking. These inducible chimeric proteins also allowed us to demonstrate that LMP1 mediated NF-kappa B activation is an immediate event following activation of LMP1.