Repression of the minimal hla-b promoter by c-myc and p53 occurs through independent mechanisms

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• 作者：Griffioen ; Marieke ; Steegenga ; Wilma T. ; Ouwerkerk ; Ilse J. M. ; Peltenburg ; Lucy T. C. ; Jochemsen ; Aart G. ; et. al.
• 关键词：C-myc ; p53 ; HLA-B ; Promoter ; Transcription
• 刊名：Molecular Immunology
• 出版年：1998
• 出版时间：September 1, 1998
• 年：1998
• 卷：35
• 期：13
• 页码：829-835
• 全文大小：1.39 M

文摘

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.