Nuclear localization of hypoxia-inducible factor-2alpha in bovine arterial endothelial cells.
Nuclear localization of hypoxia-inducible factor-2alpha in bovine arterial endothelial cells.
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DOI：
10.1006/mcbr.1999.0160
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发表时间：
1999-08-01
期刊：
影响因子：
--
通讯作者：
Imura, N
中科院分区：
文献类型：
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作者：
Hara, S;Kobayashi, C;Imura, N
缺氧诱导因子(HIF)-2α是新近发现的一种缺氧诱导转录因子，在血管内皮细胞中大量表达。与HIF-1α一样，HIF-2α与芳烃受体核转运体形成异源二聚体复合体，上调低氧诱导基因，如血管内皮生长因子。我们在本研究中发现，使用绿色荧光蛋白(GFP)融合载体，HIF-2α和HIF-1α在牛动脉内皮细胞(BAEC)中的亚细胞定位不同。HIF-1α定位于常氧细胞的胞浆，并在低氧诱导下从胞浆移位到胞核。相反，即使在常氧条件下，HIF-2α也明显定位于BAEC的胞核。HIF-2α和HIF-1α在BAEC中的调节可能不同。我们进一步表明，HIF-2α的核定位被蛋白质C末端的缺失或单一氨基酸取代所抑制。Lys737和Arg738周围的氨基酸序列是HIF-2α的核定位信号。
Hypoxia-inducible factor (HIF)-2alpha is a recently identified hypoxia-inducible transcription factor abundantly expressed in vascular endothelial cells. As well as HIF-1alpha, HIF-2alpha forms a heterodimeric complex with the aryl hydrocarbon receptor nuclear translocator and upregulates hypoxia-inducible genes such as vascular endothelial growth factor. We found in this study that using green fluorescent protein (GFP) fusion constructs, the subcellular localization of HIF-2alpha was different from that of HIF-1alpha in bovine arterial endothelial cells (BAEC). HIF-1alpha was localized in the cytoplasm under normoxic cells and translocated from the cytoplasm into the nucleus in response to hypoxic induction. In contrast, HIF-2alpha was clearly localized in the nucleus of BAEC even under normoxic conditions. The regulation of HIF-2alpha might differ from that of HIF-1alpha in BAEC. We further showed that nuclear localization of HIF-2alpha was inhibited by either deletion or a single amino acid substitution within the C-terminal end of the protein. The amino acid sequence surrounding Lys737 and Arg738 functions as a nuclear localization signal of HIF-2alpha.