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Journal of Virology, April 1999, p. 2770-2780, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activated Mouse Notch1 Transactivates Epstein-Barr Virus Nuclear Antigen 2-Regulated Viral Promoters

Heike Höfelmayr,* Lothar J. Strobl, Charlotte Stein, Gerhard Laux, Gabriele Marschall, Georg W. Bornkamm, and Ursula Zimber-Strobl

Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, Munich, Germany

Received 21 December 1998/Accepted 30 December 1998

Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for B-cell immortalization by EBV, most probably by its ability to transactivate a number of cellular and viral genes. EBNA2-responsive elements (EBNA2REs) have been identified in several EBNA2-regulated viral promoters, each of them carrying at least one RBP-Jkappa recognition site. RBP-Jkappa recruits EBNA2 to the EBNA2RE and, once complexed to EBNA2, is converted from a repressor into an activator. An activated form of the cellular receptor Notch also interacts with RBP-Jkappa , providing a link between EBNA2 and Notch signalling. To determine whether activated Notch is able to transactivate EBNA2-responsive viral promoters, we performed cotransfection experiments with activated mouse Notch1 (mNotch1-IC) and luciferase constructs of the BamHI C, LMP1, and LMP2A promoters. We present here evidence that mNotch1-IC transactivates viral promoters known to be regulated by EBNA2. As shown for EBNA2, mutations or deletions of the RBP-Jkappa sites diminish or eliminate mNotch1-IC-mediated transactivation of the promoters, pointing to an essential role for Notch-RBP-Jkappa interaction. In addition to RBP-Jkappa , other cellular factors may bind within the EBNA2REs of viral promoters. While some factors appear to play an important role in both EBNA2- and mNotch1-IC-mediated transactivation, others are only important for the activity of either EBNA2 or mNotch1-IC. We could observe specific mNotch1-IC-responsive regions, thereby throwing more light upon which cofactors interact with EBNA2 and mNotch1-IC, thus enabling them to become functionally transactivators in vivo.

* Corresponding author. Mailing address: Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Hämatologikum, Marchioninistr. 25, D-81377 München, Germany. Phone: 49-89-7099515. Fax: 49-89-7099500. E-mail: hoefelmayr{at}gsf.de.

Journal of Virology, April 1999, p. 2770-2780, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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