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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Altschul SF, Gish W, Miller W, Myers EW and Lipman DJ. . 1990 J. Mol. Biol. 215: 403–410.
Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Seguin C, Tuffnell PS and Barrell BG. . 1984 Nature 310: 207–211.
Baichwal VR and Sugden B. . 1988 Oncogene 2: 461–467.
Baichwal VR and Sugden B. . 1989 Oncogene 4: 67–74.
Bissonnette RP, Echeverri F, Mahboubi A and Green DR. . 1992 Nature 359: 552–554.
Cepko CL, Roberts BE and Mulligan RC. . 1984 Cell 37: 1053–1062.
Cohen JI and Lekstrom K. . 1999 J. Virol. 73: 7627–7632.
Decaussin G, Leclerc V and Ooka T. . 1995 J. Virol. 69: 7309–7314.
Decaussin G, Sbih-Lammali F, De Turenne-Tessier M, Bouguermouh AM and Ooka T. . 2000 Cancer Res. 60: 5584–5588.
De Thé G. . 1982 Epidemiology of Epstein-Barr virus and associated diseases in man. In B. Roizman (ed.), The Herpesviruses vol.1 Plenum Publishing. pp.25–103.
De Turenne-Tessier M, Jolicoeur P and Ooka T. . 1997 Virus Res. 52: 73–85.
Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ and Hancock DC. . 1992 Cell 69: 119–128.
Graham FL and Van der Eb AJ. . 1973 Virology 52: 456–464.
Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW and Weinberg RA. . 1999 Nature 400: 464–468.
Hayes DP, Brink AA, Vervoort MB, Middeldorp JM, Meijer CJ, van Den Brule AJ. . 1999 Mol. Pathol. 52: 97–103.
Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E and Rickinson A. . 1991 Cell 65: 1107–1115.
Higuchi R. . 1990 Recombinant PCR, in M. A. Inns (ed). PCR protocols: a guide to methods and applications. Academic Press, Inc., San Diego, California. pp. 177–183.
Huen DS, Henderson SA, Croom-Carter D and Rowe M. . 1995 Oncogene 10: 549–560.
Izumi KM, Kaye KM and Kieff E. . 1997 Proc. Natl. Acad. Sci. USA 94: 1447–1452.
Izumi KM and Kieff E. . 1997 Proc. Natl. Acad. Sci. USA 94: 12592–12597.
Kaye KM, Izumi KM and Kieff E. . 1993 Proc. Natl. Acad. Sci. USA 90: 9150–9154.
Kieff E. . 1996 Epstein-Barr Virus and its replication. In. Fields Virology, Third Edition. B.N. Fields, D.M. Knipe, P.M. Howley et al. (eds) Lippincott-Raven Publishers, Philadelphia.
Klein G. . 1973 The Epstein-Barr virus. In: Kaplan, A.S. (ed). The Herpesviruses, Academic Press, New York. pp521.
Land H, Parada LF and Weinberg RA. . 1983 Nature 304: 596–602.
Lu QL, Elia G, Lucas S and Thomas JA. . 1993 Int. J. Cancer 53: 29–35.
Mannick JB, Cohen JI, Birkenbach M, Marchini A and Kieff E. . 1991 J. Virol. 65: 6826–6837.
Martin JM, Veis D, Korsmeyer SJ and Sugden B. . 1993 J. Virol. 67: 5269–5278.
Mitchell T and Sugden B. . 1995 J. Virol. 69: 2968–2976.
Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C and Kieff E. . 1995 Cell 80: 389–399.
Ooka T and Calender A. . 1980 Virology 104: 219–223.
Ooka T, Calender A, De Turenne M and Daillie J. . 1983 J. Virol. 46: 187–195.
Ooka T and Sixbey JW. . 1991 Springer Seminars in Immunopathology -Epstein-Barr virus immunopathology. T. Ooka and J.W. Sixbey (eds). Springer International, New York 13 No 2.: pp 233–247.
Pearson WR and Lipman DJ. . 1988 Proc. Natl. Acad. Sci. USA 85: 2444–2448.
Reed JC, Haldar S, Croce CM and Cuddy MP. . 1990 Mol. Cell. Biol. 10: 4370–4374.
Rickinson AB and Kieff E. . 1996 Epstein-Barr Virus, in Fields B.N., Knipe D.M., Howley P.M.(eds): Fields Virology, (ed 3) Vol 2 New York, NY, Lippincott-Raven. pp. 2396.
Rowe M, Peng-Pilon M, Huen DS, Hardy R, Croom-Carter D, Lundgren E and Rickinson AB. . 1994 J. Virol. 68: 5602–5612.
Ruf IK, Ryhne PW, Yang H, Borza CM, Hutt-Fletcher LM, Cleveland JL and Sample JT. . 1999 Mol. Cell. Biol. 19: 1651–1660.
Sanchez-Garcia I and Grütz G. . 1995 Proc. Natl. Acad. Sci. USA 92: 5287–5291.
Sbih-Lammali F, Berger F, Busson P and Ooka T. . 1996 Virology 222: 64–74.
Shen YM. . 1982 Mol. Cell. Biol. 2: 1145–1154.
Stockbine LD, Cohen JI, Farrah T, Lyman SD, Wagener F, DuBose RF, Armitage RJ and Spriggs MK. . 1998 J. Virol. 72: 4015–4021.
Tanner JE, Wei MX, Ahmad A, Alfieri C, Taylor P, Ooka T and Menezes J. . 1997 J. Inf. Diseases 175: 38–46.
Tao Q, Srivastava G, Loke SL and Ho FC. . 1994 J. Clin. Pathol. 47: 589–591.
Tomkinson B, Robertson E and Kieff E. . 1993 J. Virol. 67: 2014–2025.
Vaux DL. . 1993 Proc. Natl. Acad. Sci. USA 90: 786–789.
Wagner AJ, Small MB and Hay N. . 1993 Mol. Cell. Biol. 13: 2432–2440.
Wang D, Liebowitz D and Kieff E. . 1985 Cell 43: 831–840.
Wang D, Liebowitz D and Kieff E. . 1988 J. Virol. 62: 2337–2346.
Wei MX and Ooka T. . 1989 The EMBO Journal 8: 2897–2903.
Wei MX, Moulin JC, Decaussin G, Berger F and Ooka T. . 1994 Cancer Res. 54: 1843–1848.
Wei MX, De Turenne-Tessier M, Decaussin G, Benet G and Ooka T. . 1997 Oncogene 14: 3073–3082.
Wigler M, Pellicer A, Silverstein S, Axel R, Urlaub G and Chasin L. . 1979 Proc. Natl. Acad. Sci. USA 76: 1373–1376.
Zhang CX, Decaussin G, Daillie J and Ooka T. . 1988 J. Virol. 62: 1862–1869.
zur Hausen A, Brink AA, Craanen ME, Middeldorp JM, Meijer CJ and van Den Brule AJ. . 2000 Cancer Res. 60: 2745–2748.
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).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204217
Keywords
This article is cited by
-
Sequence analysis of Epstein-Barr virus (EBV) early genes BARF1 and BHRF1 in NK/T cell lymphoma from Northern China
Virology Journal (2015)
-
BARF1 gene silencing triggers caspase-dependent mitochondrial apoptosis in Epstein-Barr virus-positive malignant cells
Journal of Biosciences (2015)
-
Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1
Nature Structural & Molecular Biology (2012)
-
Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma
Infectious Agents and Cancer (2010)
-
ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway
Journal of Translational Medicine (2009)