| pubmed-article:12464608 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12464608 | lifeskim:mentions | umls-concept:C0679729 | lld:lifeskim |
| pubmed-article:12464608 | lifeskim:mentions | umls-concept:C0812201 | lld:lifeskim |
| pubmed-article:12464608 | lifeskim:mentions | umls-concept:C0378796 | lld:lifeskim |
| pubmed-article:12464608 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:12464608 | lifeskim:mentions | umls-concept:C0162493 | lld:lifeskim |
| pubmed-article:12464608 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:12464608 | pubmed:dateCreated | 2003-2-24 | lld:pubmed |
| pubmed-article:12464608 | pubmed:abstractText | Interactions between Ets family members and a variety of other transcription factors serve important functions during development and differentiation processes, e.g. in the hematopoietic system. Here we show that the endothelial basic helix-loop-helix PAS domain transcription factor, hypoxia-inducible factor-2alpha (HIF-2alpha) (but not its close relative HIF-1alpha), cooperates with Ets-1 in activating transcription of the vascular endothelial growth factor receptor-2 (VEGF-2) gene (Flk-1). The receptor tyrosine kinase Flk-1 is indispensable for angiogenesis, and its expression is closely regulated during development. Consistent with the hypothesis that HIF-2alpha controls the expression of Flk-1 in vivo, we show here that HIF-2alpha and Flk-1 are co-regulated in postnatal mouse brain capillaries. A tandem HIF-2alpha/Ets binding site was identified within the Flk-1 promoter that acted as a strong enhancer element. Based on the analysis of transgenic mouse embryos, these motifs are essential for endothelial cell-specific reporter gene expression. A single HIF-2alpha/Ets element conferred strong cooperative induction by HIF-2alpha and Ets-1 when fused to a heterologous promoter and was most active in endothelial cells. The physical interaction of HIF-2alpha with Ets-1 was demonstrated and localized to the HIF-2alpha carboxyl terminus and the autoinhibitory exon VII domain of Ets-1, respectively. The deletion of the DNA binding and carboxyl-terminal transactivation domains of HIF-2alpha, respectively, created dominant negative mutants that suppressed transactivation by the wild type protein and failed to synergize with Ets-1. These results suggest that the interaction between HIF-2alpha and endothelial Ets factors is required for the full transcriptional activation of Flk-1 in endothelial cells and may therefore represent a future target for the manipulation of angiogenesis. | lld:pubmed |
| pubmed-article:12464608 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:12464608 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12464608 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12464608 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:12464608 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:CookeJ TJT | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:BreierGeorgG | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:HeidenreichRe... | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:KappelAndreas... | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:PlateKarlK | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:FlammeIngoI | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:SiewekeMichae... | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:ElvertGerdG | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:EnglmeierUrsu... | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:LanzStephanS | lld:pubmed |
| pubmed-article:12464608 | pubmed:author | pubmed-author:RauterManuelM | lld:pubmed |
| pubmed-article:12464608 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12464608 | pubmed:day | 28 | lld:pubmed |
| pubmed-article:12464608 | pubmed:volume | 278 | lld:pubmed |
| pubmed-article:12464608 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12464608 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12464608 | pubmed:pagination | 7520-30 | lld:pubmed |
| pubmed-article:12464608 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:12464608 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12464608 | pubmed:articleTitle | Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). | lld:pubmed |
| pubmed-article:12464608 | pubmed:affiliation | Zentrum für Molekulare Medizin der Universität zu Köln, Joseph-Stelzmann-Strasse 9, 50931 Köln, Germany. | lld:pubmed |
| pubmed-article:12464608 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12464608 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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