Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR
Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR
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DOI：
10.1074/jbc.273.11.6417
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发表时间：
1998-03-13
影响因子：
4.8
通讯作者：
Levy, AP
中科院分区：
文献类型：
--
作者：
Levy, NS;Chung, SM;Levy, AP
血管内皮生长因子(VEGF)是一种强有力的血管生成因子，其在低氧条件下的表达在很大程度上是由于其mRNA的稳定性增加所致。在这里，我们表明HUR与通过低氧调节血管内皮生长因子mRNA稳定性的元件具有高亲和力和特异性。抑制Hur的表达可消除低氧诱导的血管内皮细胞生长因子mRNA稳定性的增加。HUR的过表达增加了血管内皮生长因子mRNA的稳定性。然而，这只在低氧细胞中有效发生。我们进一步证明，血管内皮生长因子mRNA的稳定性在体外是可以概括的。使用S-100提取物，我们发现重组人HUR的加入显著稳定了血管内皮生长因子的mRNA。这些数据支持Hur在低氧诱导的血管内皮细胞生长因子mRNA低氧稳定中的重要作用。
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.