Chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds to a peroxisome proliferator-responsive element and antagonizes peroxisome proliferator-mediated signaling.
Peroxisome proliferators form a family of diverse xenobiotic compounds that includes hypolipidemic agents, herbicides, and plasticizers. These compounds activate transcription of a subset of nuclear genes including those encoding peroxisomal fatty acid beta-oxidation enzymes, whose elevated activities can lead to hepatocarcinogenesis. Induction of the genes encoding fatty acyl-CoA oxidase and hydratase-dehydrogenase, the first and second enzymes of the pathway, is mediated by peroxisome proliferator-activated nuclear receptors (PPARs) that bind to upstream responsive elements (PPREs) through heterodimerization with retinoid X receptors. We demonstrate that the chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1), another member of the nuclear hormone receptor superfamily, binds to the hydratase-dehydrogenase PPRE in vitro and in vivo and antagonizes PPAR-dependent signaling. These data suggest that members of the COUP-TF family play a role in modulating receptor-mediated activation of peroxisome proliferator-responsive genes.
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
K S
KS
Miyata
B
B
Zhang
S L
SL
Marcus
J P
JP
Capone
R A
RA
Rachubinski
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D051838:COUP Transcription Factor I; D002460:Cell Line; D002645:Chickens; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C497589:NR2F1 protein, human; C497591:Nr2f1 protein, rat; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D010047:Ovalbumin; D008156:Luciferases