A gain-of-function mutation in the HIF2A gene in familial erythrocytosis
A gain-of-function mutation in the HIF2A gene in familial erythrocytosis
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DOI：
10.1056/nejmoa073123
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发表时间：
2008-01-10
影响因子：
158.5
通讯作者：
Lee, Frank S.
中科院分区：
文献类型：
--
作者：
Percy, Melanie J.;Furlow, Paul W.;Lee, Frank S.
缺氧诱导因子（HIF）α有三种异构体，对全身氧气供需的持续平衡至关重要。HIF -α是一种转录因子，可调节多种过程，包括红细胞生成、血管生成和细胞代谢。我们描述了一个红细胞增多症家族，其HIF2A基因存在突变，该基因编码HIF - 2α蛋白。我们的功能研究表明，这种突变导致HIF - 2α蛋白稳定，并提示野生型HIF - 2α在成人中对促红细胞生成素的产生具有调节作用。
Hypoxia-inducible factor (HIF) alpha, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. HIF-alpha is a transcription factor that modulates a wide range of processes, including erythropoiesis, angiogenesis, and cellular metabolism. We describe a family with erythrocytosis and a mutation in the HIF2A gene, which encodes the HIF-2 alpha protein. Our functional studies indicate that this mutation leads to stabilization of the HIF-2 alpha protein and suggest what wild-type HIF-2 alpha regulates erythropoietin production in adults.