Tumor-derived Variants of Epstein-Barr Virus Latent Membrane Protein 1 Induce Sustained Erk Activation and c-Fos

摘要: Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a proven oncogene that essential for transformation human B cells by the virus. LMP1 induces constitutive activation several signal transduction pathways involving nuclear factor κB, phosphatidylinositol 3-kinase/Akt, and mitogen-activated kinases (MAPK) p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated (Erk). Sequencing isolated from panel EBV+ cell lymphomas identified three different variants LMP1, each distinct B95.8 prototype isoform. All tumor as well isoform were able to induce rapid p38 phosphorylation Akt JNK activation. Additionally all showed similar ability activate κB. In contrast, only tumor-derived induced prolonged Erk c-Fos expression. Sequence analysis revealed two amino acids, 212 366, shared but B95.8. Point mutation either acids (glycine serine) or 366 (serine threonine) variant version was sufficient gain function characterized sustained subsequent induction binding AP1 site. Our results indicate enhanced stabilize can be localized in C terminus LMP1.