Differential sub-nuclear distribution of hypoxia-inducible factors (HIF)-1 and -2 alpha impacts on their stability and mobility.
Differential sub-nuclear distribution of hypoxia-inducible factors (HIF)-1 and -2 alpha impacts on their stability and mobility.
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DOI：
10.1098/rsob.160195
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发表时间：
2016-09
期刊：
影响因子：
5.8
通讯作者：
See V
中科院分区：
文献类型：
--
作者：
Taylor SE;Bagnall J;Mason D;Levy R;Fernig DG;See V
细胞对低氧的适应是通过低氧诱导因子(HIF)介导的复杂的基因表达程序来实现的。氧不稳定的α亚基HIF-1α/-2α与HIF-1β形成异源二聚体转录因子，调节基因表达。低氧诱导因子-1α和低氧诱导因子-2α具有相似的结构域结构，并与相同的共同序列结合。然而，它们具有不同的氧依赖稳定性，并激活不同的基因。为了更好地了解这些差异，我们使用荧光显微镜来确定精确的定位和动力学。我们观察到HIF-1α在细胞核内均匀分布，而HIF-2α定位于斑点状。我们证明了HIF-2α斑点的数量、大小和迁移率与细胞的氧合作用无关，并且HIF-2α分子能够以不依赖于氧的方式在斑点和核质之间进行交换。HIF-2α在斑点中的浓度可能解释了它比HIF-1α更稳定的原因，其较慢的迁移率可能提供了一种基因特异性的机制。
Cellular adaptation to hypoxia occurs via a complex programme of gene expression mediated by the hypoxia-inducible factor (HIF). The oxygen labile alpha subunits, HIF-1α/-2α, form a heterodimeric transcription factor with HIF-1β and modulate gene expression. HIF-1α and HIF-2α possess similar domain structure and bind to the same consensus sequence. However, they have different oxygen-dependent stability and activate distinct genes. To better understand these differences, we used fluorescent microscopy to determine precise localization and dynamics. We observed a homogeneous distribution of HIF-1α in the nucleus, while HIF-2α localized into speckles. We demonstrated that the number, size and mobility of HIF-2α speckles were independent of cellular oxygenation and that HIF-2α molecules were capable of exchanging between the speckles and nucleoplasm in an oxygen-independent manner. The concentration of HIF-2α into speckles may explain its increased stability compared with HIF-1α and its slower mobility may offer a mechanism for gene specificity.
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DOI：
10.1083/jcb.152.5.1099
发表时间：
2001-03-05
期刊：
The Journal of cell biology
影响因子：
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作者：
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影响因子：
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影响因子：
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DOI：
10.1016/j.bbamcr.2007.12.006
发表时间：
2008-03-01
影响因子：
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DOI：
10.1006/mcbr.1999.0160
发表时间：
1999-08-01
期刊：
Molecular cell biology research communications : MCBRC
影响因子：
--
作者：
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Imura, N