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首页> 外文期刊>Molecular and Cellular Biology >The receptor-DNA complex determines the retinoid response: a mechanism for the diversification of the ligand signal.
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The receptor-DNA complex determines the retinoid response: a mechanism for the diversification of the ligand signal.

机译：受体-DNA复合物决定类维生素A反应：配体信号多样化的机制。

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To obtain insights into the principles governing the complex biological responses to retinoids, we have analyzed the ligand sensitivities of various retinoid receptor-DNA complexes. We find that different retinoid receptor heterodimers show distinct activation patterns with various response elements while a given heterodimer can be activated at different retinoic acid concentrations on different response elements. In vitro binding experiments suggest that the same retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer can have different ligand affinities, depending on the response element it is bound to. The differential responses of a particular receptor heterodimer with various retinoic acid responsive elements can be enhanced through the use of conformationally restricted retinoids. RAR- and RXR-selective retinoids can also synergistically activate the receptor heterodimers, indicating that both partners in the heterodimer can contribute to ligand-induced transcriptional activation. However, the relative influence of the RAR or RXR partner is specific for each response element. Together, our data demonstrate that it is the receptor-DNA complex and not the receptor alone that determines the ligand response. This flexibility allows for a highly pleiotropic retinoid response. Furthermore, conformationally restricted retinoids can accentuate the differential responses and exhibit a certain degree of gene selectivity by differentially activating the RAR or RXR component in the context of a given response element.
机译：为了深入了解控制类维生素A的复杂生物反应的原理，我们分析了各种类维生素A受体-DNA复合物的配体敏感性。我们发现，不同的类维生素A受体异二聚体显示出具有各种响应元件的不同激活模式，而给定的异二聚体可以在不同的响应元件上以不同的维甲酸浓度被激活。体外结合实验表明，相同的视黄酸受体-类视黄醇X受体（RAR-RXR）异二聚体可以具有不同的配体亲和力，具体取决于它所结合的反应元件。通过使用构象受限的类维生素A，可以增强特定受体异二聚体与各种视黄酸响应元件的差异响应。 RAR和RXR选择性类维生素A也可以协同激活受体异二聚体，表明异二聚体中的两个伴侣都可以促进配体诱导的转录激活。但是，RAR或RXR伙伴的相对影响对于每个响应元素都是特定的。总之，我们的数据表明决定配体反应的是受体-DNA复合物，而不是单独的受体。这种灵活性允许高度多效类视黄醇的反应。此外，在给定的响应元件的情况下，通过差异性地激活RAR或RXR成分，构象受限的类维生素A可以加重差异反应并表现出一定程度的基因选择性。

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