Negative regulation of hypoxia-inducible genes by the von Hippel Lindau protein
Negative regulation of hypoxia-inducible genes by the von Hippel Lindau protein
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DOI：
10.1073/pnas.93.20.10595
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发表时间：
1996-10-01
影响因子：
11.1
通讯作者：
Goldberg, MA
中科院分区：
文献类型：
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作者：
Iliopoulos, O;Levy, AP;Goldberg, MA
von Hippel-Lindau蛋白（pVHL）的失活与肾癌和中枢神经系统血管母细胞瘤的发病机制有关。这些是高度血管化的肿瘤，过度产生血管生成肽，如血管内皮生长因子/血管渗透因子发现缺乏野生型pVHL的肾癌细胞在常氧和缺氧条件下均产生编码VEGF/VPF、葡萄糖转运蛋白GLUT 1和血小板衍生生长因子B链的mRNA。进入这些细胞的pVHL特异性抑制了这些mRNA在常氧条件下的产生，从而恢复了它们之前描述的缺氧诱导谱。因此，pVHL似乎在环境氧张力变化产生的信号转导中发挥着关键作用。
Inactivation of the von Hippel-Lindau protein (pVHL) has been implicated in the pathogenesis of renal carcinomas and central nervous system hemangioblastomas. These are highly vascular tumors which overproduce angiogenic peptides such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), Renal carcinoma cells lacking wild-type pVHL were found to produce mRNAs encoding VEGF/VPF, the glucose transporter GLUT1, and the platelet-derived growth factor B chain under both normoxic and hypoxic conditions, Reintroduction of wild-type, but not mutant, pVHL into these cells specifically inhibited the production of these mRNAs under normoxic conditions, thus restoring their previously described hypoxia-inducible profile, Thus, pVHL appears to play a critical role in the transduction of signals generated by changes in ambient oxygen tension.