HYPOXIC STABILIZATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR MESSENGER-RNA BY THE RNA-BINDING PROTEIN HUR

Vascular endothelial growth factor (VEGF) is a potent angiogenic facto r whose expression is dramatically induced by hypoxia due in large par t to an increase in the stability of its mRNA. Here we show that HuR b inds 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 marked ly. These data support the critical role of HuR in mediating the hypox ic stabilization of VEGF mRNA by hypoxia.