Caenorhabditis elegans orthologs of the aryl hydrocarbon receptor and its heterodimerization partner the aryl hydrocarbon receptor nuclear translocator.
Caenorhabditis elegans orthologs of the aryl hydrocarbon receptor and its heterodimerization partner the aryl hydrocarbon receptor nuclear translocator.
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DOI：
10.1073/pnas.95.6.2844
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发表时间：
1998-03
影响因子：
11.1
通讯作者：
J. Powell-Coffman;C. Bradfield;William B. Wood
中科院分区：
文献类型：
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作者：
J. Powell-Coffman;C. Bradfield;William B. Wood
芳烃受体(AHR)是一种配体激活的转录因子，到目前为止只在脊椎动物中被描述，它介导了某些环境污染物的许多致癌和致畸作用。在这里，我们描述了AHR及其二聚化伙伴AHR核转运蛋白(ARNT)在线虫中的同源基因，分别由ahr-1和aha-1基因编码。相应的蛋白质AHR-1和AHA-1与它们在哺乳动物中的同源蛋白具有相同的生化性质。具体地说，AHR-1与HSP90形成紧密的结合，AHR-1和AHA-1相互作用，结合含有具有序列特异性的哺乳动物异源反应元件的DNA片段。酵母表达研究表明，线虫AHR-1和脊椎动物AHR一样，需要某种形式的翻译后激活。此外，这一要求依赖于预测的介导HSP90与配体结合的结构域的存在。初步实验表明，如果AHR-1是配体激活的，它的配体光谱与哺乳动物受体的光谱不同：线虫AHR-1不是由二恶英类似物标记的光亲和性，也不被酵母系统中的β-萘黄酮激活。在一种简单的、遗传上易驯化的无脊椎动物中发现这些基因，应该有助于阐明AHR-1的功能并识别其内源调节因子。
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, until now described only in vertebrates, that mediates many of the carcinogenic and teratogenic effects of certain environmental pollutants. Here, we describe orthologs of AHR and its dimerization partner AHR nuclear translocator (ARNT) in the nematode Caenorhabditis elegans, encoded by the genes ahr-1 and aha-1, respectively. The corresponding proteins, AHR-1 and AHA-1, share biochemical properties with their mammalian cognates. Specifically, AHR-1 forms a tight association with HSP90, and AHR-1 and AHA-1 interact to bind DNA fragments containing the mammalian xenobiotic response element with sequence specificity. Yeast expression studies indicate that C. elegans AHR-1, like vertebrate AHR, requires some form of post-translational activation. Moreover, this requirement depends on the presence of the domains predicted to mediate binding of HSP90 and ligand. Preliminary experiments suggest that if AHR-1 is ligand-activated, its spectrum of ligands is different from that of the mammalian receptor: C. elegans AHR-1 is not photoaffinity labeled by a dioxin analog, and it is not activated by beta-naphthoflavone in the yeast system. The discovery of these genes in a simple, genetically tractable invertebrate should allow elucidation of AHR-1 function and identification of its endogenous regulators.