N-terminal domain of BARF1 gene encoded by Epstein-Barr virus is essentialfor malignant transformation of rodent fibroblasts and activation of BCL-2

The BARF1 gene encoded by the Epstein-Barr virus induces morphological chan ges, loss of contact inhibition and anchorage independence in established r odent Balb/c3T3 fibroblast, BARF1 gene was also capable of inducing maligna nt transformation in a human Louckes B cell line. Our recent study showed t hat BARF1 gene had an ability to immortalize primary epithelial cells. Howe ver we do not know which region(s) of BARF1 protein is(are) responsible for inducing malignant transformation in established rodent cells. Using the d eletion mutants, we now localized malignant transforming region in N-termin al of BARF1 protein. The mutants lacking this region were unable to transfo rm the cells in malignant state, Furthermore, we demonstrated that only the mutants containing this region rendered the cells resistant to apoptosis i nduced by serum deprivation. Surprisingly, the BARF1 gene was capable of:ac tivating anti-apoptotic Bcl-2 expression and this activation was due to the N-terminal transforming region. These data suggest that the cooperation of BARF1 with Bcl-2 is essential for the induction of malignant transformatio n.