Epstein-Barr Virus Latent-Infection Membrane Proteins are Palmitoylated and Raft-Associated: Protein 1 Binds to the Cytoskeleton through TNF Receptor Cytoplasmic Factors

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-04, Vol.98 (8), p.4675-4680
• Main Authors: Higuchi, Masaya, Izumi, Kenneth M., Kieff, Elliott
• Format: Article
• Language: English
• Subjects: Antibodies; B lymphocytes; Biological Sciences; Cell Line, Transformed; Cell lines; Cellular biology; Cysteine - metabolism; Cytoskeleton; Cytoskeleton - metabolism; Enzyme Activation; Epstein-Barr virus; Gels; Herpesvirus 4, Human - metabolism; Humans; JNK Mitogen-Activated Protein Kinases; Kidney cells; Lipid Metabolism; Lipids; LMP1 protein; LMP2A protein; Membranes; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; Palmitic Acid - metabolism; Protein Binding; Protein Isoforms - chemistry; Protein Isoforms - metabolism; Proteins; Rafts; Receptors; Receptors, Tumor Necrosis Factor - metabolism; Signal Transduction; Viral Matrix Proteins - chemistry; Viral Matrix Proteins - metabolism; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.081075298

Epstein-Barr virus encodes integral membrane proteins LMP1 and LMP2A in transformed lymphoblastoid cell lines. We now find that LMP1 associates with the cell cytoskeleton through a tumor necrosis factor receptor-associated factor-interacting domain, most likely mediated by tumor necrosis factor receptor-associated factor 3. LMP1 is palmitoylated, and the transmembrane domains associate with lipid rafts. Mutation of LMP1 cysteine-78 abrogates palmitoylation but does not affect raft association or NF-κB or c-Jun N-terminal kinase activation. LMP2A also associates with rafts and is palmitoylated but does not associate with the cell cytoskeleton. The associations of LMP1 and LMP2A with rafts and of LMP1 with the cell cytoskeleton are likely to effect interactions with cell proteins involved in shape, motility, signal transduction, growth, and survival.