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首页> 外文期刊>Molecular and Cellular Biology >Activation of the inducible orphan receptor gene nur77 by serum growth factors: dissociation of immediate-early and delayed-early responses.
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Activation of the inducible orphan receptor gene nur77 by serum growth factors: dissociation of immediate-early and delayed-early responses.

机译：血清生长因子对可诱导的孤儿受体基因nur77的激活：立即早期反应和延迟早期反应分离。

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We have characterized the genetic elements that mediate the transcriptional activation of nur77, a growth factor-inducible gene encoding a member of the steroid/thyroid hormone receptor superfamily. Although initially identified as a serum-inducible immediate-early gene with expression kinetics similar to those of c-fos, we found that transcriptional activation of nur77 by serum growth factors in fibroblasts is in fact composed of two components: an immediate-early component, which can occur in the absence of de novo protein synthesis, and a delayed-early component, which is dependent on de novo protein synthesis. The expression of nur77 following serum stimulation reflects the superimposition of immediate-early and delayed-early expression. Immediate-early and delayed-early expression can be dissociated from one another by deletion or base substitution mutations of the nur77 promoter. Immediate-early expression of nur77 is mediated primarily by sequences located between nucleotides -86 and -126 upstream of the transcription start site. This region includes a sequence that resembles but differs from the CArG element found in other serum-inducible promoters. Upstream of the CArG-like element is a potential binding site for a transcription factor of the Ets family; the presence of this site is required for significant transcriptional induction. Delayed-early expression of nur77 is mediated by multiple AP-1-like and GC-rich elements, which can interact with products of immediate-early genes such as Fos/Jun and Zif268, respectively. Furthermore, we show that Zif268 can activate transcription of the nur77 promoter, suggesting that it may play a role in the delayed-early expression of nur77.
机译：我们已经表征了介导nur77的转录激活的遗传元件，nur77是生长激素诱导型基因，编码类固醇/甲状腺激素受体超家族的成员。尽管最初被鉴定为具有与c-fos相似的表达动力学的血清诱导型即早基因，但我们发现成纤维细胞中血清生长因子对nur77的转录激活实际上由两个部分组成：即早组分，它可能在没有从头蛋白质合成的情况下发生，并且延迟早期成分取决于从头蛋白质合成。血清刺激后nur77的表达反映了立即早期表达和延迟早期表达的叠加。早期表达和早期延迟表达可以通过nur77启动子的缺失或碱基取代突变而彼此分离。 nur77的立即早期表达主要由位于转录起始位点上游核苷酸-86和-126之间的序列介导。该区域包括类似于但不同于在其他血清诱导型启动子中发现的CArG元件的序列。 CArG样元件的上游是Ets家族转录因子的潜在结合位点。该位点的存在是重要的转录诱导所必需的。 nur77的早期延迟表达是由多种AP-1样和富含GC的元件介导的，它们可以分别与即早基因如Fos / Jun和Zif268的产物相互作用。此外，我们显示Zif268可以激活nur77启动子的转录，表明它可能在nur77的早期延迟表达中起作用。

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