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首页> 外文期刊>Molecular and Cellular Biology >A cellular factor stimulates ligand-dependent release of hsp90 from the basic helix-loop-helix dioxin receptor.
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A cellular factor stimulates ligand-dependent release of hsp90 from the basic helix-loop-helix dioxin receptor.

机译：细胞因子刺激hsp90从基本螺旋-环-螺旋二恶英受体的配体依赖性释放。

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In response to dioxin, the nuclear basic helix-loop-helix (bHLH) dioxin receptor forms a complex with the bHLH partner factor Arnt that regulates target gene transcription by binding to dioxin-responsive sequence motifs. Previously, we have demonstrated that the latent form of dioxin receptor present in extracts from untreated cells is stably associated with molecular chaperone protein hsp90, and Arnt is not a component of this complex. Here, we used a coimmunoprecipitation assay to demonstrate that the in vitro-translated dioxin receptor, but not Arnt, is stably associated with hsp90. Although it showed ligand-binding activity, the in vitro-translated dioxin receptor failed to dissociate from hsp90 upon exposure to ligand. Addition of a specific fraction from wild-type hepatoma cells, however, to the in vitro-expressed receptor promoted dioxin-dependent release of hsp90. This stimulatory effect was mediated via the bHLH dimerization and DNA-binding motif of the receptor. Moreover, ligand-dependent release of hsp90 from the receptor was not promoted by fractionated cytosolic extracts from mutant hepatoma cells which are deficient in the function of bHLH dioxin receptor partner factor Arnt. Thus, our results provide a novel model for regulation of bHLH factor activity and suggest that derepression of the dioxin receptor by ligand-induced release of hsp90 may require bHLH-mediated concomitant recruitment of an additional cellular factor, possibly the structurally related bHLH dimerization partner factor Arnt. In support of this model, addition of in vitro-expressed wild-type Arnt, but not a mutated form of Arnt lacking the bHLH motif, promoted release of hsp90 from the dioxin receptor in the presence of dioxin.
机译：响应二恶英，核碱性螺旋-环-螺旋（bHLH）二恶英受体与bHLH伴侣因子Arnt形成复合物，后者通过与二恶英响应性序列基序结合来调节靶基因的转录。以前，我们已经证明存在于未经处理的细胞提取物中的二恶英受体的潜在形式与分子伴侣蛋白hsp90稳定相关，而Arnt不是该复合物的成分。在这里，我们使用了免疫共沉淀实验来证明体外翻译的二恶英受体而不是Arnt与hsp90稳定相关。尽管它显示出配体结合活性，但体外翻译的二恶英受体在暴露于配体后仍无法从hsp90上解离。然而，从野生型肝癌细胞中加入特定的部分到体外表达的受体促进了hsp90的二恶英依赖性释放。这种刺激作用是通过受体的bHLH二聚化和DNA结合基序介导的。而且，来自突变肝细胞的分级分离的胞质提取物不能促进hsp90从受体的配体依赖性释放，所述分离的肝细胞提取物缺乏bHLH二恶英受体伴侣因子Arnt的功能。因此，我们的结果为调节bHLH因子的活性提供了一个新颖的模型，并表明配体诱导的hsp90释放对二恶英受体的抑制可能需要bHLH介导的同时募集额外的细胞因子，可能是与结构相关的bHLH二聚体伴侣因子阿特为了支持该模型，在存在二恶英的情况下，添加体外表达的野生型Arnt而不是缺少bHLH基序的Arnt突变形式可以促进hsp90从二恶英受体中释放。

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