N-myc suppresses major histocompatibility complex class I gene expression through down-regulation of the p50 subunit of NF-kappa B.
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.
van 't Veer
L J
LJ
Division of Molecular Genetics, Massachusetts General Hospital, Charlestown 02129.
Beijersbergen
R L
RL
Bernards
R
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D016259:Genes, myc; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma; D009838:Oligodeoxyribonucleotides; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D015500:Chloramphenicol O-Acetyltransferase