Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells

EMBO J. 1996 Jan 15;15(2):375-82.

Abstract

A conditional mutant of Epstein-Barr virus nuclear antigen 2 (EBNA2) regulated by estrogen was employed to study the effect of EBNA2 on the cellular phenotype. Activation of EBNA2 in lymphoblastoid cell lines (LCLs) and in B cell lymphoma lines resulted in down-regulation of cell surface IgM and Ig-mu steady-state RNA expression. In LCLs, activation of EBNA2 is required for maintaining proliferation, whereas in Burkitt's lymphoma (BL) cell lines with t(8;14) translocations, activation of EBNA2 induces growth arrest. In these cells, Northern and nuclear run-on analyses revealed rapid simultaneous repression of Ig-mu and c-myc transcription as early as 30 min after activation of EBNA2. Since c-myc expression is under the control of the Ig heavy chain locus in BL cell lines with a t(8;14) translocation, we propose that Ig-mu and c-myc are down-regulated by EBNA2 through a common mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / metabolism*
  • Blotting, Northern
  • Burkitt Lymphoma / genetics
  • Cell Division
  • Cell Nucleus / metabolism
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 8
  • DNA-Binding Proteins / metabolism*
  • Epstein-Barr Virus Nuclear Antigens
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc*
  • Humans
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin mu-Chains / biosynthesis
  • Kinetics
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Receptors, Antigen, B-Cell / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism*
  • Time Factors
  • Transcription, Genetic
  • Transfection
  • Translocation, Genetic
  • Tumor Cells, Cultured

Substances

  • Antigens, Viral
  • DNA-Binding Proteins
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin M
  • Immunoglobulin mu-Chains
  • Proto-Oncogene Proteins c-myc
  • Receptors, Antigen, B-Cell
  • Recombinant Fusion Proteins
  • Repressor Proteins