The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia
The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia
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DOI：
10.1073/pnas.141234698
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发表时间：
2001-07-03
影响因子：
11.1
通讯作者：
Powell-Coffman, JA
中科院分区：
文献类型：
--
作者：
Jiang, HQ;Guo, R;Powell-Coffman, JA
缺氧诱导因子是一种异二聚体转录复合物，在正常哺乳动物发育或肿瘤进展过程中调节细胞和全身对低氧水平（缺氧）的反应。在这里，我们提供的证据表明，一个类似的复合物介导了秀丽隐杆线虫对缺氧的反应。该复合体由HIF-1和AHA-1组成，它们分别由线虫的低氧诱导因子(HIF) α和β亚基的同系物C编码。hif-1突变体在标准的实验室条件下没有表现出严重的缺陷，但它们不能适应缺氧，尽管野生型动物可以在1%的氧气中生存和繁殖，但大多数hif-1缺陷的动物在这些条件下死亡。我们发现HIF-1：绿色荧光蛋白融合蛋白在缺氧诱导下表达，随后在再氧化时减少，HIF-1和aha-1在大多数细胞类型中都有表达，并且基因产物可以共免疫沉淀。我们得出结论，缺氧信号的机制可能在后生动物中是保守的。此外，我们发现在hif-1突变体中ha -1的核定位被破坏。这一发现表明异源二聚化可能是ha -1有效核易位的先决条件。
Hypoxia-inducible factor, a heterodimeric transcription complex, regulates cellular and systemic responses to low oxygen levels (hypoxia) during normal mammalian development or tumor progression. Here, we present evidence that a similar complex mediates response to hypoxia in Caenorhabditis elegans. This complex consists of HIF-1 and AHA-1, which are encoded by C, elegans homologs of the hypoxia-inducible factor (HIF) alpha and beta subunits, respectively. hif-1 mutants exhibit no severe defects under standard laboratory conditions, but they are unable to adapt to hypoxia, Although wild-type animals can survive and reproduce in 1% oxygen, the majority of hif-1-defective animals die in these conditions. We show that the expression of an HIF-1:green fluorescent protein fusion protein is induced by hypoxia and is subsequently reduced upon reoxygenation, Both hif-1 and aha-1 are expressed in most cell types, and the gene products can be coimmunoprecipitated. We conclude that the mechanisms of hypoxia signaling are likely conserved among metazoans. Additionally, we find that nuclear localization of AHA-1 is disrupted in an hif-1 mutant. This finding suggests that heterodimerization may be a prerequisite for efficient nuclear translocation of AHA-1.