The in vivo binding site for oncoprotein c-Myc in the promoter for Epstein-Barr virus (EBV) encoding RNA (EBER) 1 suggests a specific role for EBV in lymphomagenesis

Hans Helmut Niller, Daniel Salamon, Karin Ilg, Anita Koroknai, Ferenc Banati, Gerald Bäuml, Ovidiu Ludwig Rücker, Fritz Schwarzmann, Hans Wolf, Janos Minarovits

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Epstein-Barr virus (EBV) was isolated in the 1960s from the African childhood tumor, Burkitt's Lymphoma (BL), characterized by the translocation of the c-myc gene into one of the immunoglobulin loci. Due to the extreme discrepancy between the widespread dissemination of EBV infection and the overall rarity of EBV-related tumors, it remains an open question whether EBV is really a human tumor virus, and if so, what specific contribution EBV may have to tumorigenesis. Material/Methods: Protein binding at the EBER locus of EBV was analyzed by genomic footprinting electrophoretic mobility shift, reporter gene assay, and chromatin immunoprecipitation in a panel of six B-cell lines. Results: Several novel in vivo protein binding sites were found in the EBER locus. Among those, a prominent binding site, 130 base pairs upstream of the EBER 1 gene, contains two E-boxes providing a consensus sequence for binding of the transcription factor and oncoprotein c-Myc to the EBV genome. Conclusion: Based on the discovery of a binding site for c-Myc in the EBV genome, a new molecular model for the specific role of EBV as a causal factor in the origin of endemic Burkitt's Lymphoma is proposed. Translocated and deregulated c-myc directly activates and maintains the antiapoptotic functions of the EBER locus in a single EBV-infected B cell undergoing the germinal center (GC) reaction. With the balance shifted towards cell survival, the oncogenic potential of the pro-apoptotic c-Myc protein is unmasked in the translocated GC cell. This single translocated and surviving cell is the founder cell of an endemic BL. The new model reinstitutes EBV as a real human tumor virus.

Original languageEnglish
Pages (from-to)HY1-HY9
JournalMedical Science Monitor
Volume9
Issue number1
Publication statusPublished - Jan 1 2003

Keywords

  • Burkitt's lymphoma
  • Genomic footprints
  • Germinal center
  • Hodgkin's Disease
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Medicine(all)

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