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Transcriptional regulation of the vascular endothelial growth factor gene.
Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor that is overexpressed in a number of human cancers and in hypoxic conditions. Hypoxia inducible factor (HIF) transcription factors are the essential regulators of VEGF expression. Additional factors, including nuclear factor-kappaB (NF-kappaB), and early growth response proteins (Egr-1 and ELK) also transactivate the VEGF promoter, and influence VEGF expression. The detailed mechanisms of transactivation of the VEGF promoter by these factors are not fully understood. We have identified a novel cis-acting element in the human and mouse VEGF promoter region that plays an important role in transactivation by NF-kappaB. Gel shift and mutagenesis experiments have identified a 19 bp sequence that is essential for NF-kappaB activation of the human VEGF promoter. A consensus site for NF-kappaB binding is present in this sequence and NF-kappaB binding to this element is evident in vivo. This element is adjacent to a region in which NF-kappaB and Egr-1 have previously been reported to bind and is therefore referred to as the kappaB site. Transfection of the kappaB site deletion mutants in HEK293 cells has shown that these factors, NF-kappaB and Egr-1, can bind the same sequences of the kappaB site, but the binding of NF-kappaB to this site is highly dependent on stimulus (TNF-alpha, IL-1beta) and cell type (endothelial, lymphoid or hepatoma cells).Wake up, Long Island! The President’s favorite time of year is here — summertime and the last installment of my week-long series, “The Great Backyard Bird Count.” In this, the final episode, we cover the other four houses of the Tri-State area — New York, New Jersey and the Hudson River counties to the north — plus the Catskills and Adirondacks, the Mohawk region, Massachusetts, Vermont, and

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