MHC class I gene expression is negatively regulated by the proto-oncogene, c-jun.
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.
Howcroft
T K
TK
Experimental Immunology Branch, NCI, NIH, Bethesda, MD 20892.
Richardson
J C
JC
Singer
D S
DS
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D016758:Genes, jun; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism
C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun