HYPOXIA-INDUCIBLE FACTOR-1 IS A BASIC-HELIX-LOOP-HELIX-PAS HETERODIMER REGULATED BY CELLULAR O-2 TENSION
HYPOXIA-INDUCIBLE FACTOR-1 IS A BASIC-HELIX-LOOP-HELIX-PAS HETERODIMER REGULATED BY CELLULAR O-2 TENSION
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DOI：
10.1073/pnas.92.12.5510
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发表时间：
1995-06-06
影响因子：
11.1
通讯作者：
SEMENZA, GL
中科院分区：
文献类型：
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作者：
WANG, GL;JIANG, BH;SEMENZA, GL
缺氧诱导因子1（HIF-1）存在于缺氧条件下培养的哺乳动物细胞中，是缺氧细胞中促红细胞生成素基因增强子介导的转录激活所必需的。我们发现，这两个HIF-1亚基是含有PAS结构域的碱性螺旋-环-螺旋蛋白质，其存在于果蝇Per和Sim蛋白质中，并且在哺乳动物ARNT和AHR蛋白质中，HIF-1 α与Sim最密切相关。HIF-1 β是一系列ARNT基因产物，因此可以与HLF-1 α或AHR异源二聚体化。HIF-1 α和HIF-1 β（ARNT）RNA和蛋白质水平在暴露于1%O-2的细胞中诱导，并在细胞恢复到20%Oz时迅速衰减，这与HIF-1作为缺氧转录反应介导剂的作用一致。
Hypoxia-inducible factor 1 (HIF-1) is found In mammalian cells cultured under reduced O-2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins, HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HLF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O-2 and decayed rapidly upon return of the cells to 20% Oz, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.