Downregulation of MHC class I expression due to interference with p105-NF kappa B1 processing by Ad12E1A.
We have previously demonstrated that expression of major histocompatibility complex (MHC) class I genes is repressed in baby rat kidney cells transformed by early region 1 of oncogenic adenovirus type 12 (Ad12E1). Reduced expression of MHC class I antigens contributes to the escape of Ad12-transformed cells from T-cell-mediated immune surveillance and to tumour induction. In this study, we show that repression of MHC class I expression by Ad12E1A is mediated via the H2TF1 element of the MHC class I promoter. This element binds NF kappa B and KBF1, two factors which play a major role in the regulation of MHC class I expression in vivo. In extracts from Ad12E1-transformed cells, binding of KBF1 and NF kappa B to the H2TF1 element is decreased. This is caused by reduced production of p50-NF kappa B1, the 50 kDa subunit shared by KBF1 and NF kappa B, due to interference with p105-NF kappa B1 processing by Ad12-13S-E1A protein. Overexpression of the p105-NF kappa B1 cDNA, or of a truncated p105-NF kappa B1 cDNA that codes for p50-NF kappa B1, restores MHC class I expression in Ad12E1-transformed cells. These data demonstrate that downregulation of MHC class I expression in Ad12E1-transformed cells is due to interference with processing of p105-NF kappa B1 by the Ad12-13S-E1A protein.
Schouten
G J
GJ
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, University of Leiden, The Netherlands.
van der Eb
A J
AJ
Zantema
A
A
D000256:Adenoviridae; D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000096:biosynthesis*; D007668:Kidney; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D017500:Adenovirus E1A Proteins; D018076:DNA, Complementary; D006183:H-2 Antigens; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors