The first exon of Ad12 E1A excluding the transactivation domain mediates differential binding of COUP-TF and NF-kappa B to the MHC class I enhancer in transformed cells.
The major histocompatibility complex class I enhancer is the target for adenovirus-12 E1A-mediated down-regulation of class I transcription. In Ad12 transformed rodent cells, the class I enhancer is down-regulated through increased binding of the repressor COUP-TF to the R2 element and decreased binding of the activator NF-kappa B (p50/p65) to the R1 element. The reduced surface levels of class I antigens contribute to the tumorigenic potential of Ad12 transformed cells by favoring their immunoescape from cytotoxic T-lymphocytes. Previous studies using transformed cells containing hybrid Ad5/Ad12 E1A (plus Ad12 E1B) genes have indicated that sequences within the first exon of the 266R Ad12 E1A gene are required for class I down-regulation and tumorigenesis. In this study we demonstrate that these same sequences, which exclude the Ad12 CR3 transactivation domain, are also required for increased COUP-TF binding to the R2 element and decreased NF-kappa B binding to the R1 element of the class I enhancer. We further show that diminished NF-kappa B binding is not due to a lack of NF-kappa B1-p50 in the nuclei of Ad12 transformed rat cells.
Kushner
D B
DB
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pereira
D S
DS
Liu
X
X
Graham
F L
FL
Ricciardi
R P
RP
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D051838:COUP Transcription Factor I; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005091:Exons; D005805:Genes, MHC Class I; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D016328:NF-kappa B; C497591:Nr2f1 protein, rat; D014157:Transcription Factors