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Journal of Virology, February 2000, p. 1727-1735, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Activated Notch1 Modulates Gene Expression in B Cells Similarly to Epstein-Barr Viral Nuclear Antigen 2

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

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

Received 12 July 1999/Accepted 15 November 1999

Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch transactivate genes by interacting with the transcription factor RBP-Jkappa . The viral protein EBNA2 may hence be regarded as a functional equivalent of an activated Notch receptor. Until now, nothing has been known about the physiological role of Notch signaling in B cells. Here we investigated whether activated Notch can induce the same phenotypic changes as EBNA2 in Burkitt's lymphoma cells. An estrogen receptor fusion protein of the intracellular part of mouse Notch 1 (mNotch1-IC), mimicking in the presence of estrogen a constitutively active Notch receptor, was stably transfected into the Burkitt's lymphoma cell lines BL41-P3HR1 and HH514. Northern blot analysis revealed that the LMP2A gene is induced by Notch-IC in the presence of estrogen, whereas increased expression of LMP1 could be detected only if cycloheximide was simultaneously added. Concerning the cellular genes regulated by EBNA2, Notch-IC was able to upregulate CD21 but not CD23 expression. Immunoglobulin µ (Igµ) expression, which is downregulated by EBNA2, was also negatively regulated by Notch-IC. Similarly to EBNA2, Notch-IC was able to repress c-myc expression, which is under the control of the immunoglobulin heavy-chain locus in Burkitt's lymphoma cells with a t(8;14) translocation. The data show that Notch-IC is able to participate in gene regulation in B cells.

* Corresponding author. Mailing address: GSF-National Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistr. 25, D-81377 Munich, Germany. Phone: 49-89-7099 501. Fax: 49-89-7099 500. E-mail: Bornkamm{at}gsf.de.

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

Journal of Virology, February 2000, p. 1727-1735, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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