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J Virol, July 1998, p. 6034-6039, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Replacement of the Intracellular Region of the Notch1 Receptor by Epstein-Barr Virus Nuclear Antigen 2

Takashi Sakai,1,dagger Yoshihito Taniguchi,1 Kumiko Tamura,1,Dagger Shigeru Minoguchi,1 Takataro Fukuhara,1 Lothar J. Strobl,2 Ursula Zimber-Strobl,2 George W. Bornkamm,2 and Tasuku Honjo1,*

Department of Medical Chemistry, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan,1 and Institute für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, 81377 Munich, Germany2

Received 1 December 1997/Accepted 30 March 1998

The intracellular region (RAMIC) of the mouse Notch1 receptor interacts with RBP-J/CBF-1, which binds to the DNA sequence CGTGGGAA and suppresses differentiation by transcriptional activation of genes regulated by RBP-J. Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for immortalization of human B cells by the virus. EBNA2 is a pleiotropic activator of viral and cellular genes and is targeted to DNA at least in part by interacting with RBP-J. We found that EBNA2 and the Notch1 RAMIC compete for binding to RBP-J, indicating that their interaction sites on RBP-J overlap at least partially. EBNA2 and Notch1 RAMIC transactivated the same set of viral and host promoters, i.e., the EBNA2 response element of the Epstein-Barr virus TP1 and the HES-1 promoter. Furthermore, EBNA2 functionally replaced the Notch1 RAMIC by suppressing differentiation of C2C12 myoblast progenitor cells.

* Corresponding author. Mailing address: Department of Medical Chemistry, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan. Phone: 81-75-753-4371. Fax: 81-75-753-4388. E- mail: honjo @mfour .med .kyoto-u .ac .jp.

dagger Present address: Division of Gene Regulatorics, The Institute for Enzyme Research, The University of Tokushima, Tokushima 770, Japan.

Dagger Present address: Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0636.

J Virol, July 1998, p. 6034-6039, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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