Activation of a Ras-MAPK-dependent pathway by Epstein-Barr virus latent membrane protein 1 is essential for cellular transformation

Abstract

The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is the only EBV protein which possesses the properties of an oncogene. In studies initiated to evaluate the mechanisms involved in EBV-induced malignant transformation, the extracellular response kinase (ERK) 1/2 were found to be activated 2 days after EBV infection of purified resting human B cells. Transfection studies in Rat-1 fibroblasts, an established rodent cell line, showed that LMP1 mediates ERK 1/2 activation. Cotransfection experiments with a dominant negative ras mutant demonstrated that such MAPK activation occurs via a ras-dependent pathway. Finally, cotransfection studies showed that ras activation is required for LMP-1-mediated malignant transformation of Rat-1 cells.