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PMID: 9621066 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional replacement of the intracellular region of the Notch1 receptor by Epstein-Barr virus nuclear antigen 2.

Journal of virology ·Vol. 72 ·No. 7 ·1998-07-00 ·Pages 6034-9

Sakai T, Taniguchi Y, Tamura K, Minoguchi S, Fukuhara T, Strobl LJ, Zimber-Strobl U, Bornkamm GW, Honjo T

Abstract

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.

MeSH Terms
Animals COS Cells Cell Differentiation/drug effects DNA-Binding Proteins/metabolism Epstein-Barr Virus Nuclear Antigens/physiology Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein Membrane Proteins/physiology Muscles/cytology Nuclear Proteins Promoter Regions, Genetic Receptor, Notch1 Receptors, Cell Surface Transcription Factors Transcriptional Activation
Chemicals
DNA-Binding Proteins Epstein-Barr Virus Nuclear Antigens Immunoglobulin J Recombination Signal Sequence-Binding Protein Membrane Proteins NOTCH1 protein, human Nuclear Proteins RBPJ protein, human Receptor, Notch1 Receptors, Cell Surface Transcription Factors
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sakai T
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan.
Taniguchi Y
Tamura K
Minoguchi S
Fukuhara T
Strobl L J
Zimber-Strobl U
Bornkamm G W
Honjo T
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29 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.7.6034-6039.1998
Published
1998-07-00
Pages
6034-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110408
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.72.7.6034-6039.1998 PMC Full Text View journal details
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