N-terminal domain of BARF1 gene encoded by Epstein-Barr virus is essential for malignant transformation of rodent fibroblasts and activation of BCL-2.
The BARF1 gene encoded by the Epstein-Barr virus induces morphological changes, loss of contact inhibition and anchorage independence in established rodent Balb/c3T3 fibroblast. BARF1 gene was also capable of inducing malignant transformation in a human Louckes B cell line. Our recent study showed that BARF1 gene had an ability to immortalize primary epithelial cells. However we do not know which region(s) of BARF1 protein is(are) responsible for inducing malignant transformation in established rodent cells. Using the deletion mutants, we now localized a malignant transforming region in N-terminal of BARF1 protein. The mutants lacking this region were unable to transform the cells in malignant state. Furthermore, we demonstrated that only the mutants containing this region rendered the cells resistant to apoptosis induced by serum deprivation. Surprisingly, the BARF1 gene was capable of activating 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 transformation.
Sheng
W
W
Laboratoire de Virologie Moléculaire, UMR5537, CNRS, Faculté de Médecine R.T.H. Laënnec, Université Claude Bernard Lyon-1, Lyon, France.
Decaussin
G
G
Sumner
S
S
Ooka
T
T
D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics*
C086495:BARF1 protein, Human herpesvirus 4; D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins