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How to catch a HIF-the work of Gregg Semenza's lab on hypoxia-inducible factor 1.
Journal of Biological Chemistry ( IF 5.5 ) Pub Date : 2020-01-17 , DOI: 10.1074/jbc.cl119.012269
Martin J. Spiering

Molecular oxygen is essential for the viability and function of every cell of the animal body. Because skin, tissues, and organs impede oxygen diffusion directly from the air, molecular oxygen concentrations inside the body often are less than 5% (1), much lower than the 21% in Earth's atmosphere.As multicellular organisms evolved, this steep oxygen gradient necessitated the development of structures such as the circulatory system and of biochemical mechanisms that monitor and control oxygen levels in the body.A major player in sensing potentially harmful drops in cellular oxygen concentrations (hypoxia) is the transcription factor hypoxia-inducible factor 1 (HIF-1).2 HIF-1, and its close relative HIF-2, regulate many genes, including the erythropoietin (EPO) gene, which encodes a hormone that stimulates production of red blood cells (2, 3).One important milestone in uncovering HIF-1's pivotal role in oxygen sensing was its purification and biochemical characterization in the mid-1990s by the lab of Gregg Semenza (Fig. 1), a geneticist at Johns Hopkins University School of Medicine. This work was reported in two JBC papers recognized as Classics here (4, 5).jbc;295/3/715/F1F1F1Figure 1.Gregg Semenza and colleagues isolated and biochemically characterized the HIF-1 protein. Photo courtesy of Johns Hopkins Medicine.“JBC was the first choice,” says Semenza, referring to the publication of the first Classics article. “To me, that was a classic JBC paper.”A few years before this work, Semenza's team had found that hypoxia induces the binding of a nuclear protein to a 50-nucleotide-long enhancer region located in the 3′-flanking region of the EPO gene (2, 3). Although...

中文翻译:

如何捕捉HIF-Gregg Semenza实验室关于缺氧诱导因子1的研究。

分子氧对于动物体内每个细胞的活力和功能至关重要。由于皮肤,组织和器官直接阻止氧气从空气中扩散,因此体内的分子氧浓度通常低于5%(1),远低于地球大气中的21%。随着多细胞生物的进化,这种陡峭的氧梯度必需开发诸如循环系统的结构以及监测和控制体内氧气水平的生化机制-1).2 HIF-1及其近亲HIF-2调节许多基因,包括促红细胞生成素(EPO)基因,该基因编码刺激红血球生成的激素(2,3)。揭示HIF-1在氧气传感中的关键作用的一个重要里程碑是1990年代中期由约翰·霍普金斯大学医学院遗传学家Gregg Semenza的实验室进行的纯化和生化表征(图1)。这项工作在JBC的两篇公认的经典文献中得到了报道(4,5)。jbc; 295/3/715 / F1F1F1图1.Gregg Semenza及其同事分离了HIF-1蛋白并对其进行了生化表征。Semenza说,“ JBC是第一选择,”他指的是第一本经典著作的出版​​。“在我看来,这是经典的JBC论文。”在这项工作之前的几年,Semenza的研究小组发现低氧诱导核蛋白与位于3'侧翼区域的50个核苷酸长的增强子区域结合。 EPO基因(2,3)。虽然...
更新日期:2020-01-17
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