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-kappaB activation.
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-kappaB activation domain (CTAR2) have been reported. We have now mapped the NF-kappaB 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-kappaB activation is an immediate event following activation of LMP1.
Floettmann
J E
JE
Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Rowe
M
M
D000818:Animals; D001704:Biopolymers; D018801:CD2 Antigens / Q000737:chemistry; D003062:Codon; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism
D001704:Biopolymers; D018801:CD2 Antigens; D003062:Codon; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins