N-myc suppresses major histocompatibility complex class I gene expression through down-regulation of the p50 subunit of NF-kappa B

EMBO J. 1993 Jan;12(1):195-200.

Abstract

In neuroblastoma, N-myc suppresses the expression of major histocompatibility complex (MHC) Class I antigens by reducing the binding of a nuclear factor to the enhancer-A element in the MHC Class I gene promoter. We show here that the p50 subunit of NF-kappa B is part of this complex and that expression of p50 mRNA is suppressed by N-myc. Transfection of a p50 expression vector in neuroblastoma cells that express N-myc at a high level leads to restoration of factor binding to the MHC Class I gene enhancer, restores enhancer activity and leads to re-expression of MHC Class I antigens at the cell surface. These data indicate that the p50 subunit of NF-kappa B is involved in the regulation of MHC Class I antigen expression and that N-myc down-regulates MHC Class I gene expression primarily through suppression of p50 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Blotting, Northern
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Enhancer Elements, Genetic
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Genes, MHC Class I*
  • Genes, myc*
  • HeLa Cells
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neuroblastoma
  • Oligodeoxyribonucleotides
  • Rats
  • Recombinant Proteins / metabolism
  • Suppression, Genetic*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Histocompatibility Antigens Class I
  • Macromolecular Substances
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Chloramphenicol O-Acetyltransferase