The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce apoptosis or require RIP for NF-kappa B activation

A site in the Epstein-Barr virus (EBV) transforming protein LMP1 that const itutively associates with the tumor necrosis factor receptor 1 (TNFR1)-asso ciated death domain protein TRADD to mediate NF-kappa B and c-Jun N-termina l kinase activation is critical for long-term lymphoblastoid cell prolifera tion. We now find that LMP1 signaling through TRADD differs from TNFR1 sign aling through TRADD. LMP1 needs only 11 amino acids to activate NF-kappa B or synergize with TRADD in NF-kappa B activation, while TNFR1 requires simi lar to 70 residues. Further, LMP1 does not require TRADD residues 294 to 31 2 for NF-kappa B activation, while TNFR1 requires TRADD residues 296 to 302 . LMP1 is partially blocked for NF-kappa B activation by a TRADD mutant con sisting of residues 122 to 293. Unlike TNFR1, LMP1 can interact directly wi th receptor-interacting protein (RIP) and stably associates with RIP in EBV -transformed lymphoblastoid cell lines. Surprisingly, LMP1 does not require RIP for NF-kappa B activation. Despite constitutive association with TRADD or RIP, LMP1 does not induce apoptosis in EBV-negative Burkitt lymphoma or human embryonic kidney 293 cells. These results add a different perspectiv e to the molecular interactions through which LMP1, TRADD, and RTP particip ate in B-lymphocyte activation and growth.