The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family

• Published in: Cell Vol. 80; no. 3; pp. 389 - 399
• Main Authors: Mosialos, George, Birkenbacht, Mark, Yalamanchill, Ramana, Van Arsdale, Todd, Ware, Carl, Kleff, Elliott
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.02.1995
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Antigens, Viral - physiology; B-Lymphocytes - metabolism; Base Sequence; cDNA; Cell Line, Transformed; Cell Membrane - metabolism; Cytoplasm - metabolism; Epstein-Barr virus; Herpesvirus 4, Human - metabolism; Humans; LAP1 protein; LMP-1 protein; LMP-1-associated protein; lymphocytes B; man; Mice; Models, Biological; Molecular Sequence Data; nucleotide sequence; Organ Specificity; prediction; Proteins - genetics; Proteins - metabolism; Receptors, Tumor Necrosis Factor - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - metabolism; RNA, Messenger - biosynthesis; Sequence Homology, Amino Acid; signal transduction; Signal Transduction - physiology; TNF Receptor-Associated Factor 1; TNF Receptor-Associated Factor 2; Viral Matrix Proteins - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(95)90489-1

The cytoplasmic C-terminus of Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is essential for B lymphocyte growth transformation and is now shown to interact with a novel human protein (LMP1-associated protein 1 [LAP1]). LAN is homologous to a murine protein, tumor necrosis factor receptor-associated factor 2 (TRAF2), implicated in growth signaling from the p80 TNFR. A second novel protein (EBI6), induced by EBV infection, is the human homolog of a second murine TNFR-associated protein (TRAF1). LMP1 expression causes LAPP and EBI6 to localize to LMP1 clusters in lymphoblast plasma membranes, and LMPI coimmunoprecipitates with these proteins. LAPI binds to the p80 TNFR, CD40, and the lymphotoxin-β receptor, while EBI6 associates with the p80 TNFR. The interaction of LMP1 with these TNFR family-associated proteins is further evidence for their role in signaling and links LMP1-mediated transformation to signal transduction from the TNFR family.