MHC CLASS-I GENE-EXPRESSION IS NEGATIVELY REGULATED BY THE PROTOONCOGENE, C-JUN

被引:54
|
作者
HOWCROFT, TK
RICHARDSON, JC
SINGER, DS
机构
[1] Experimental Immunology Branch, NCI, NIH, Building 10, Bethesda
来源
EMBO JOURNAL | 1993年 / 12卷 / 08期
关键词
AP-1; C-JUN; GENE EXPRESSION; MHC CLASS-I; ONCOGENE;
D O I
10.1002/j.1460-2075.1993.tb05985.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The trans-acting factor AP-1 is a heterodimeric complex composed of c-Jun and c-Fos family proteins which bind and regulate genes containing a TPA responsive enhancer element. Although AP-1 binding sites have been identified within the regulatory region of major histocompatibility complex (MHC) class I genes in vitro, the role of AP-1 in regulating MHC class I transcription in vivo has not been investigated previously. The present study demonstrates that expression of c-Jun results in decreased MHC class I promoter activity as determined in cotransfection assays of an MHC class I reporter construct with a c-Jun expression construct. The c-Jun responsive element is located between bp -440 and -431 upstream of initiation of transcription as determined both functionally and by direct binding of purified c-Jun. Furthermore, over-expression of c-Jun reduced the steady state levels of endogenous MHC class I RNA in murine L cells by approximately 10-fold. These data indicate that c-Jun/AP-1 acts as a negative trans-acting factor that down-regulates MHC class I gene expression.
引用
收藏
页码:3163 / 3169
页数:7
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