Negative regulation by the R2 element of the MHC class I enhancer in adenovirus-12 transformed cells correlates with high levels of COUP-TF binding.
The transcriptional down-regulation of the major histocompatibility complex (MHC) class I antigens in adenovirus type 12 (Ad12) transformed cells gives them the potential to escape immunosurveillance and to form tumors. The enhancer of the class I promoter is the target of transcriptional repression which is mediated by the E1A gene of Ad12. The R2 region within the class I enhancer acts as a negative element in Ad12-transformed cells and exhibits a stronger binding activity than is observed in nontumorigenic Ad5-transformed cells, which are not reduced in class I expression. The R2 element contains a nuclear hormone receptor half-site consensus sequence, AGGTCA, which is required for both the binding activity and the ability of R2 to act as a negative element in Ad12-transformed cells. In this study, we show that an orphan hormone receptor protein, COUP-TF, contributes to the differential R2 binding activity observed between Ad12- and Ad5-transformed cells. Additionally, COUP-TF was shown to bind as a dimer to the R2 element and to use the consensus AGGTCA as one half-site and its 3' flanking sequence as a probable second degenerate half-site. Since COUP-TF can act as a transcriptional repressor, we suggest that the higher COUP-TF binding activity to the R2 element in Ad12-transformed cells contributes to down-regulation of class I transcription and, consequently, tumorigenesis.
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104.
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X
Liu
R
R
Ge
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S
Westmoreland
A J
AJ
Cooney
S Y
SY
Tsai
M J
MJ
Tsai
R P
RP
Ricciardi
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D051838:COUP Transcription Factor I; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D005805:Genes, MHC Class I; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; C497589:NR2F1 protein, human; C497590:Nr2f1 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors