This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Höfelmayr, H.
Right arrow Articles by Zimber-Strobl, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Höfelmayr, H.
Right arrow Articles by Zimber-Strobl, U.

Next Article 

Journal of Virology, March 2001, p. 2033-2040, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2033-2040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Activated Notch1 Can Transiently Substitute for EBNA2 in the Maintenance of Proliferation of LMP1-Expressing Immortalized B Cells

Heike Höfelmayr, Lothar J. Strobl,dagger Gabriele Marschall, Georg W. Bornkamm, and Ursula Zimber-Strobl*

Institute for Clinical Molecular Biology and Tumor Genetics, GSF National Research Center of Environment and Health, D-81377 Munich, Germany

Received 24 August 2000/Accepted 1 December 2000

Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for immortalization of human B cells by EBV. EBNA2 and activated Notch transactivate genes by interacting with the cellular transcription factor RBP-Jkappa /CBF1. Therefore, EBNA2 can be regarded as a functional homologue of activated Notch. We have shown previously that the intracellular domain of Notch1 (Notch1-IC) is able to transactivate EBNA2-regulated viral promoters and to induce phenotypic changes in B cells similar to those caused by EBNA2. Here we investigated whether Notch1-IC can substitute for EBNA2 in the maintenance of B-cell proliferation. Using an EBV-immortalized lymphoblastoid cell line in which EBNA2 function can be regulated by estrogen, we demonstrate that murine Notch1-IC, in the absence of functional EBNA2, is unable to maintain LMP1 expression and to maintain cell proliferation. However, in a lymphoblastoid cell line expressing LMP1 independently of EBNA2, murine Notch1-IC can transiently maintain proliferation after EBNA2 inactivation. After 4 days, cell numbers do not increase further, and cells in the G2 phase of the cell cycle start to die. In contrast to EBNA2, murine Notch1-IC is unable to upregulate the expression of the c-myc gene in these cells.

* Corresponding author. Present address: Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany. Phone: 49-221-470-3416. Fax: 49-221-470-5185. E-mail: u.strobl{at}uni-koeln.de

dagger Present address: Institute for Genetics, University of Cologne, D-50931 Cologne, Germany.

Journal of Virology, March 2001, p. 2033-2040, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2033-2040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ling, P. D., Tan, J., Peng, R. (2009). Nuclear-Cytoplasmic Shuttling Is Not Required for the Epstein-Barr Virus EBNA-LP Transcriptional Coactivation Function. J. Virol. 83: 7109-7116 [Abstract] [Full Text]  
  • Kohlhof, H., Hampel, F., Hoffmann, R., Burtscher, H., Weidle, U. H., Holzel, M., Eick, D., Zimber-Strobl, U., Strobl, L. J. (2009). Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells. Blood 113: 5506-5515 [Abstract] [Full Text]  
  • Faumont, N., Durand-Panteix, S., Schlee, M., Gromminger, S., Schuhmacher, M., Holzel, M., Laux, G., Mailhammer, R., Rosenwald, A., Staudt, L. M., Bornkamm, G. W., Feuillard, J. (2009). c-Myc and Rel/NF-{kappa}B Are the Two Master Transcriptional Systems Activated in the Latency III Program of Epstein-Barr Virus-Immortalized B Cells. J. Virol. 83: 5014-5027 [Abstract] [Full Text]  
  • Kim, I.-J., Burkum, C. E., Cookenham, T., Schwartzberg, P. L., Woodland, D. L., Blackman, M. A. (2007). Perturbation of B Cell Activation in SLAM-Associated Protein-Deficient Mice Is Associated with Changes in Gammaherpesvirus Latency Reservoirs. J. Immunol. 178: 1692-1701 [Abstract] [Full Text]  
  • Carroll, K. D., Bu, W., Palmeri, D., Spadavecchia, S., Lynch, S. J., Marras, S. A. E., Tyagi, S., Lukac, D. M. (2006). Kaposi's Sarcoma-Associated Herpesvirus Lytic Switch Protein Stimulates DNA Binding of RBP-Jk/CSL To Activate the Notch Pathway. J. Virol. 80: 9697-9709 [Abstract] [Full Text]  
  • Maier, S., Santak, M., Mantik, A., Grabusic, K., Kremmer, E., Hammerschmidt, W., Kempkes, B. (2005). A Somatic Knockout of CBF1 in a Human B-Cell Line Reveals that Induction of CD21 and CCR7 by EBNA-2 Is Strictly CBF1 Dependent and that Downregulation of Immunoglobulin M Is Partially CBF1 Independent. J. Virol. 79: 8784-8792 [Abstract] [Full Text]  
  • Pages, F., Galon, J., Karaschuk, G., Dudziak, D., Camus, M., Lazar, V., Camilleri-Broet, S., Lagorce-Pages, C., Lebel-Binay, S., Laux, G., Fridman, W.-H., Henglein, B. (2005). Epstein-Barr virus nuclear antigen 2 induces interleukin-18 receptor expression in B cells. Blood 105: 1632-1639 [Abstract] [Full Text]  
  • Lee, J. M., Lee, K.-H., Farrell, C. J., Ling, P. D., Kempkes, B., Park, J. H., Hayward, S. D. (2004). EBNA2 Is Required for Protection of Latently Epstein-Barr Virus-Infected B Cells against Specific Apoptotic Stimuli. J. Virol. 78: 12694-12697 [Abstract] [Full Text]  
  • Farrell, C. J., Lee, J. M., Shin, E.-C., Cebrat, M., Cole, P. A., Hayward, S. D. (2004). Inhibition of Epstein-Barr virus-induced growth proliferation by a nuclear antigen EBNA2-TAT peptide. Proc. Natl. Acad. Sci. USA 101: 4625-4630 [Abstract] [Full Text]  
  • Kim, I.-J., Flano, E., Woodland, D. L., Lund, F. E., Randall, T. D., Blackman, M. A. (2003). Maintenance of Long Term {gamma}-Herpesvirus B Cell Latency Is Dependent on CD40-Mediated Development of Memory B Cells. J. Immunol. 171: 886-892 [Abstract] [Full Text]  
  • Johansen, L. M., Deppmann, C. D., Erickson, K. D., Coffin, W. F. III, Thornton, T. M., Humphrey, S. E., Martin, J. M., Taparowsky, E. J. (2003). EBNA2 and Activated Notch Induce Expression of BATF. J. Virol. 77: 6029-6040 [Abstract] [Full Text]  
  • Lee, J. M., Lee, K.-H., Weidner, M., Osborne, B. A., Hayward, S. D. (2002). Epstein-Barr virus EBNA2 blocks Nur77- mediated apoptosis. Proc. Natl. Acad. Sci. USA 99: 11878-11883 [Abstract] [Full Text]  
  • Gordadze, A. V., Peng, R., Tan, J., Liu, G., Sutton, R., Kempkes, B., Bornkamm, G. W., Ling, P. D. (2001). Notch1IC Partially Replaces EBNA2 Function in B Cells Immortalized by Epstein-Barr Virus. J. Virol. 75: 5899-5912 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»