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

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.

• Authors: L J van 't Veer, R L Beijersbergen, R Bernards
• Journal: The EMBO journal (EMBO J) Vol. 12 Issue 1 Pg. 195-200 (Jan 1993) ISSN: 0261-4189 [Print] England
• PMID: 8428579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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