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

被引:109
作者
Floettmann, JE [1 ]
Rowe, M [1 ]
机构
[1] UNIV WALES COLL MED,DEPT MED,CARDIFF CF4 4XX,S GLAM,WALES
关键词
EBV; LMP1; NF-KB; TNF-receptor; TRAF; signaling;
D O I
10.1038/sj.onc.1201359
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1851 / 1858
页数:8
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