Tumor necrosis factor receptor associated factor 2 is a mediator of NF-kappa B activation by latent infection membrane protein 1, the Epstein-Barr virus transforming protein.
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.
Kaye
K M
KM
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Devergne
O
O
Harada
J N
JN
Izumi
K M
KM
Yalamanchili
R
R
Kieff
E
E
Mosialos
G
G
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001667:Binding, Competitive; D002472:Cell Transformation, Viral; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2; D014763:Viral Matrix Proteins / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D011506:Proteins; C484406:TANK protein, human; D047992:TNF Receptor-Associated Factor 2; C100814:Tank protein, mouse; D014763:Viral Matrix Proteins