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Kohlhof, H. ; Hampel, F. ; Hoffmann, R.* ; Burtscher, H.* ; Weidle, U.H.* ; Hölzel, M.* ; Eick, D. ; Zimber-Strobl, U. ; Strobl, L.J.

Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells.

Blood 113, 5506-5515 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The canonical mode of transcriptional activation by both the Epstein-Barr viral protein, Epstein-Barr virus-encoded nuclear antigen 2 (EBNA2), and an activated Notch receptor (Notch-IC) requires their recruitment to RBPJ, suggesting that EBNA2 uses the Notch pathway to achieve B-cell immortalization. To gain further insight into the biologic equivalence between Notch-IC and EBNA2, we performed a genome-wide expression analysis, revealing that Notch-IC and EBNA2 exhibit profound differences in the regulation of target genes. Whereas Notch-IC is more potent in regulating genes associated with differentiation and development, EBNA2 is more potent in inducing viral and cellular genes involved in proliferation, survival, and chemotaxis. Because both EBNA2 and Notch-IC induced the expression of cell cycle associated genes, we analyzed whether Notch1-IC or Notch2-IC can replace EBNA2 in B-cell immortalization. Although Notch-IC could drive quiescent B cells into the cell cycle, B-cell immortalization was not maintained, partially due to an increased apoptosis rate in Notch-IC expressing cells. Expression analysis revealed that both EBNA2 and Notch-IC induced the expression of proapoptotic genes, but only in EBNA2-expressing cells were antiapoptotic genes strongly up-regulated. These findings suggest that Notch signaling in B cells and B-cell lymphomas is only compatible with proliferation if pathways leading to antiapototic signals are active.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter rbp-j-kappa; c-myc; binding-protein; activated notch1; direct target; cyclin d1; expression; ebna2; recombination; membrane
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 113, Heft: 22, Seiten: 5506-5515 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
POF Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501500-003
G-501400-001
PubMed ID 19339697
DOI 10.1182/blood-2008-11-190090
Scopus ID 67049097357
Erfassungsdatum 2009-12-31
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