Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene.
Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized as a product of endothelial cells. Reporter gene transfection experiments have indicated that a GATA site and an AP1 site are essential for ET-1 promoter function in endothelial cells, and GATA-2 appears to be the active GATA factor which regulates ET-1 expression. To look for interactions between AP1 and GATA-2, transactivation experiments were performed with expression vectors encoding c-Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was observed as a synergistic increase in transcriptional activity of the ET-1 reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2 was able to potentiate the action of AP1 despite deletion of the GATA site. Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this capacity to interact with AP1 may be a characteristic of all GATA family members. Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro-synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA-binding protein, indicating the association of AP1 and GATA proteins in vivo.
Kawana
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Division of Cardiology, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
Lee
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Quertermous
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Quertermous
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D001483:Base Sequence; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D016232:Endothelins; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors