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PMID: 10644343 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Activated Notch1 modulates gene expression in B cells similarly to Epstein-Barr viral nuclear antigen 2.

Journal of virology ·Vol. 74 ·No. 4 ·2000-02-00 ·Pages 1727-35

Strobl LJ, Höfelmayr H, Marschall G, Brielmeier M, Bornkamm GW, Zimber-Strobl U

Abstract

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 mu (Igmu) 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.

MeSH Terms
Animals B-Lymphocytes Binding Sites Burkitt Lymphoma Cell Membrane/metabolism DNA-Binding Proteins/genetics Down-Regulation Epstein-Barr Virus Nuclear Antigens/metabolism Estrogens/metabolism Gene Expression Regulation Herpesvirus 4, Human Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein Immunoglobulin mu-Chains/genetics Membrane Proteins/genetics,metabolism Mice Nuclear Proteins Promoter Regions, Genetic Proto-Oncogene Proteins c-myc/genetics Receptor, Notch1 Receptors, Cell Surface Receptors, Complement 3d/genetics Receptors, IgE/genetics Transcription Factors Transcription, Genetic Transcriptional Activation Transfection Tumor Cells, Cultured Up-Regulation Viral Matrix Proteins/genetics
Chemicals
DNA-Binding Proteins EBV-associated membrane antigen, Epstein-Barr virus Epstein-Barr Virus Nuclear Antigens Estrogens Immunoglobulin J Recombination Signal Sequence-Binding Protein Immunoglobulin mu-Chains Membrane Proteins NOTCH1 protein, human Notch1 protein, mouse Nuclear Proteins Proto-Oncogene Proteins c-myc RBPJ protein, human Rbpj protein, mouse Receptor, Notch1 Receptors, Cell Surface Receptors, Complement 3d Receptors, IgE Transcription Factors Viral Matrix Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Strobl L J
GSF-National Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, D-81377 Munich, Germany.
Höfelmayr H
Marschall G
Brielmeier M
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.74.4.1727-1735.2000
Published
2000-02-00
Pages
1727-35
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC111648
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.74.4.1727-1735.2000 PMC Full Text View journal details
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