M. Griffioen et al., REPRESSION OF THE MINIMAL HLA-B PROMOTER BY C-MYC AND P53 OCCURS THROUGH INDEPENDENT MECHANISMS, Molecular immunology, 35(13), 1998, pp. 829-835
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 promot
er 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 investig
ated whether c-ml:c-induced HLA-B abrogation is mediated by p53. In th
is article, it is shown that the HLA-B core promoter is indeed repress
ed by wild-type p53, making p53 a candidate for mediating c-myc-induce
d HLA-B downregulation. However, transifection 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 th
rough independent mechanisms. (C) 1998 Elsevier Science Ltd. All right
s reserved.