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PMID: 10074124 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Activated mouse Notch1 transactivates Epstein-Barr virus nuclear antigen 2-regulated viral promoters.

Journal of virology ·Vol. 73 ·No. 4 ·1999-04-00 ·Pages 2770-80

Höfelmayr H, Strobl LJ, Stein C, Laux G, Marschall G, Bornkamm GW, Zimber-Strobl U

Abstract

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.

MeSH Terms
Animals Epstein-Barr Virus Nuclear Antigens/genetics Gene Expression Regulation, Viral HeLa Cells Herpesvirus 4, Human/genetics Humans Membrane Proteins/genetics Mice Promoter Regions, Genetic Receptor, Notch1 Receptors, Cell Surface Transcription Factors Transcriptional Activation
Chemicals
Epstein-Barr Virus Nuclear Antigens Membrane Proteins NOTCH1 protein, human Notch1 protein, mouse Receptor, Notch1 Receptors, Cell Surface Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Höfelmayr H
Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, Munich, Germany. hoefelmayr@gsf.de
Strobl L J
Stein C
Laux G
Marschall G
Bornkamm G W
Zimber-Strobl U
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.4.2770-2780.1999
Email
hoefelmayr@gsf.de
Published
1999-04-00
Pages
2770-80
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC104034
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.73.4.2770-2780.1999 PMC Full Text View journal details
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