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

Oncogene volume 20, pages 1176–1185 (2001)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by C.N.R.S, Fondation de France, the Fédération Nationale des groupements des Entreprises françaises dans la Lutte contre le Cancer (GEFLUC), Association pour la Recherche sur le Cancer (ARC) contract No 9528 and Programme de Recherche Fondamentale en Microbiologie, Maladies Infectieuses et Parasitaires (Ministère de l'Education National de la Recherche et de la Technologie, France).

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  1. Laboratoire de Virologie Moléculaire, UMR5537, CNRS, Faculté de Médecine R.T.H. Laënnec, Université Claude Bernard Lyon-1, Lyon, France

    Wang Sheng, Gisèle Decaussin, Stéphanie Sumner & Tadamasa Ooka

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  1. Wang Sheng
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Sheng, W., Decaussin, G., Sumner, S. et al. N-terminal domain of BARF1 gene encoded by Epstein-Barr virus is essential for malignant transformation of rodent fibroblasts and activation of BCL-2. Oncogene 20, 1176–1185 (2001). https://doi.org/10.1038/sj.onc.1204217

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