Authors: | Levy, N. S.; Chung, S.; Furneaux, H.; Levy, A. P. |
Article Title: | Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR |
Abstract: | Vascular endothelial growth factor (VEGF) is a potent angiogenic factor whose expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. Here we show that HuR binds with high affinity and specificity to the element that regulates VEGF mRNA stability by hypoxia. Inhibition of HuR expression abrogates the hypoxia-mediated increase in VEGF mRNA stability. Overexpression of HuR increases the stability of VEGF mRNA. However, this only occurs efficiently in hypoxic cells. We further show that the stabilization of VEGF mRNA can be recapitulated in vitro. Using an S-100 extract, we show that the addition of recombinant HuR stabilizes VEGF mRNA markedly. These data support the critical role of HuR in mediating the hypoxic stabilization of VEGF mRNA by hypoxia. |
Keywords: | vasculotropin; controlled study; protein expression; vascular endothelial growth factor a; human cell; cells, cultured; gene overexpression; protein binding; dna, antisense; angiogenesis; hypoxia; rna binding protein; gene expression regulation; rna-binding proteins; molecular sequence data; messenger rna; rna, messenger; recombinant protein; protein induction; base sequence; binding site; protein s 100; anoxia; half-life; antigens, surface; protein rna binding; regulatory sequences, nucleic acid; vascular endothelial growth factors; endothelial growth factors; human; priority journal; article; lymphokines |
Journal Title: | Journal of Biological Chemistry |
Volume: | 273 |
Issue: | 11 |
ISSN: | 0021-9258 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Date Published: | 1998-03-13 |
Start Page: | 6417 |
End Page: | 6423 |
Language: | English |
DOI: | 10.1074/jbc.273.11.6417 |
PUBMED: | 9497373 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |