Nuclear translocation of hypoxia-inducible factors (HIFs):: Involvement of the classical importin α/β pathway
Nuclear translocation of hypoxia-inducible factors (HIFs):: Involvement of the classical importin α/β pathway
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DOI：
10.1016/j.bbamcr.2007.12.006
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发表时间：
2008-03-01
影响因子：
5.1
通讯作者：
Koehler, Matthias
中科院分区：
文献类型：
--
作者：
Depping, Reinhard;Steinhoff, Amrei;Koehler, Matthias
低氧诱导因子是脊椎动物细胞氧稳态的关键环节。HIF-α亚基的稳定化和随后的核定位导致靶基因如VEGF、EPO和Glut1的激活。转录因子如HIF-1α通过核孔复合体进入细胞核受核转运受体的调节。因此，核质穿梭可以通过促进转录因子在两个区段之间的细胞交通来调节转录活性。在这里，我们报告了低氧诱导因子与核转运蛋白受体Importinα/β的特异性相互作用。HIF-1α、-1β和HIF-2α与导入蛋白α1、α3、α5和α7结合。HIF-1α与α重要蛋白的直接相互作用依赖于蛋白质C末端区域内的功能性核定位信号。相反，假设的N端NLS是不有效的。我们的发现为低氧诱导因子的核转运调控机制提供了新的见解。(C)2007 Elsevier B.V.保留所有权利。
Hypoxia-inducible factors are the key elements in the essential process of oxygen homeostasis of vertebrate cells. Stabilisation and subsequent nuclear localisation of HIF-alpha subunits results in the activation of target genes such as vegf, epo and glut1. The passage of transcription factors e.g. HIF-1 alpha into the nucleus through the nuclear pore complex is regulated by nuclear transport receptors. Therefore nucleocytoplasmic shuttling can regulate transcriptional activity by facilitating the cellular traffic of transcription factors between both compartments. Here, we report on the identification of specific interactions of hypoxia-inducible factors with nuclear transport receptors importin alpha/beta. HIF-1 alpha, -1 beta, and HIF-2 alpha are binding to importin alpha 1, alpha 3, alpha 5, and alpha 7. The direct interaction of HIF-1 alpha to alpha importins is dependent on a functional nuclear localisation signal within the C-terminal region of the protein. In contrast, the supposed N-terminal NLS is not effective. Our findings provide new insight into the mechanism of the regulation of nuclear transport of hypoxia-inducible factors. (c) 2007 Elsevier B.V. All rights reserved.