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| TRANSCRIPTIONAL REGULATION OF THE RAT VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE BY HYPOXIA |
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| Author(s): LEVY AP, LEVY NS, WEGNER S, GOLDBERG MA |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 270 Issue: 22 Pages: 13333-13340 Published: JUN 2 1995 |
| Times Cited: 608 References: 56 |
| Abstract: Vascular endothelial growth factor (VEGF), a potent angiogenic factor and endothelial cell-specific mitogen, is up-regulated by hypoxia. However, the mechanism(s) responsible for hypoxic induction of VEGF has not been clearly delineated. We report that the steady state VEGF mRNA levels are increased 12 +/- 0.6-fold, but the transcriptional rate for VEGF is increased only 3.1 +/- O.6-fold by hypoxia in PC12 cells. In order to investigate cis-regulatory sequences which mediate this response to hypoxia, we cloned the rat genomic sequences encoding VEGF and identified a 28-base pair element in the 5' promoter that mediates hypoxia-inducible transcription in transient expression assays. This element has sequence and protein binding similarities to the hypoxia-inducible factor 1 binding site within the erythropoietin 3' enhancer. Post-transcriptional mechanisms have also been suggested to play a role in the hypoxic induction of VEGF. Evidence is provided that a frequently used polyadenylation site is 1.9 kilobases downstream from the translation termination codon for rat VEGF. This site is 1.5 kilobases further downstream from the polyadenylation site previously reported for VEGF. This new finding reveals sequence motifs in the 3'-untranslated region that may mediate VEGF mRNA stability. |
| Document Type: Article |
| Language: English |
Addresses:
1. BRIGHAM & WOMENS HOSP, DEPT MED, DIV CARDIOL, BOSTON, MA 02115 USA
2. BRIGHAM & WOMENS HOSP, DEPT MED, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA
3. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: RB439 |
| ISSN: 0021-9258 |
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