Elsevier

Immunobiology

Volume 193, Issues 2–4, July 1995, Pages 238-247
Immunobiology

C-Myc Represses Transiently Transfected HLA Class I Promoter Sequences not Locus-Specifically

https://doi.org/10.1016/S0171-2985(11)80549-8Get rights and content

Abstract

Overexpression of the c-myc oncogene is frequently accompanied by downregulation of Major Histocompatibility Complex (MHC, HLA in humans) class I antigens. In human melanoma c-myc overexpression downmodulates HLA-B expression, whereas HLA-A is hardly affected. Repression of HLA-B is mediated through the core promoter, containing a CAAT-box and a non-conventional TATA-box. We show evidence that in transient transfection assays the HLA-A2 and HLA-B7 promoters are repressed by cmyc to the same extent. Therefore, other sequences of the HLA-A and HLA-B genes, possibly intron/exon sequences, should contribute to the locus B-specificity of the downregulation. Furthermore, c-myc does not seem to alter binding of protein complexes to the CAAT- or TATA-box of HLA-B7 or HLA-A2 in gel retardation assays. Comparison of promoters repressed by c-myc reveals a weak consensus sequence of the initiator (Inr) element: TCA(+1)YYYNY. The presence of a TCA sequence in the initiator region of the MHC class I promoter makes downregulation by c-myc through the Inr likely. We speculate that the Inr contributes to MHC class I promoter activity by stimulating recruitment of TFIID to the weak, non-conventional TATA-box, thereby making it susceptible to repression by c-myc through the Inr.

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  • Cited by (0)

    *

    Dr. Peter I. Schrier, University Hospital Leiden, Department of Clinical Oncology, P.O. 9600, 2300 RC Leiden, The Netherlands

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