Hypoxic Stabilization of Vascular Endothelial Growth Factor mRNA by the RNA-binding Protein HuR
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...
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Veröffentlicht in: | The Journal of biological chemistry 1998-03, Vol.273 (11), p.6417-6423 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.273.11.6417 |