Repression of the minimal HLA-B promoter by c-myc and p53 occurs through independent mechanisms.
Major Histocompatibility Complex (MHC, HLA in humans) class I antigens play an important role in cellular immunology by presenting antigens to T cells. Downregulation of MHC class I expression is thought to be a mechanism by which tumor cells escape from T cell-mediated lysis. In primary human melanomas and melanoma cell lines, HLA-B expression is frequently downmodulated, correlating with elevated expression of the c-myc oncogene. Transfection experiments have shown that c-myc induces HLA-B downregulation through a -68 to +13 base pairs (bp) core promoter fragment, containing CCAAT and TATA-like (TCTA) boxes. Since (i) c-myc has been reported to activate the human p53 promoter and (ii) p53 is capable of repressing a large array of basal promoters, we investigated whether c-myc-induced HLA-B abrogation is mediated by p53. In this article, it is shown that the HLA-B core promoter is indeed repressed by wild-type p53, making p53 a candidate for mediating c-myc-induced HLA-B downregulation. However, transfection of c-myc into p53-null cell lines still resulted in suppression of the basal HLA-B promoter, demonstrating that c-myc and p53 repress the minimal HLA-B promoter through independent mechanisms.
Griffioen
M
M
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
Steegenga
W T
WT
Ouwerkerk
I J
IJ
Peltenburg
L T
LT
Jochemsen
A G
AG
Schrier
P I
PI
D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation; D005805:Genes, MHC Class I; D017930:Genes, Reporter; D016259:Genes, myc; D016158:Genes, p53; D015235:HLA-B Antigens / Q000235:genetics*; D015793:HLA-B7 Antigen / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D015235:HLA-B Antigens; D015793:HLA-B7 Antigen; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D008156:Luciferases