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Alternative retinoid X receptor (RXR) ligands

机译:替代类视黄醇X受体(RXR)配体

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摘要

Retinoid X receptors (RXRs) control a wide variety of functions by virtue of their dimerization with other nuclear hormone receptors (NRs), contributing thereby to activities of different signaling pathways. We review known RXR ligands as transcriptional modulators of specific RXR-dimers and the associated biological processes. We also discuss the physiological relevance of such ligands, which remains frequently a matter of debate and which at present is best met by member(s) of a novel family of retinoids, postulated as Vitamin A5. Through comparison with other natural, but also with synthetic ligands, we discuss high diversity in the modes of ligand binding to RXRs resulting in agonistic or antagonistic profiles and selectivity towards specific subtypes of permissive heterodimers. Despite such diversity, direct ligand binding to the ligand binding pocket resulting in agonistic activity was preferentially preserved in the course of animal evolution pointing to its functional relevance, and potential for existence of other, species-specific endogenous RXR ligands sharing the same mode of function.
机译:随表X受体(RXRS)通过与其他核激素受体(NRS)的二聚化来控制各种功能,从而促进不同信号通路的活动。我们认为已知的RXR配体作为特定RXR-二聚体和相关生物过程的转录调节剂。我们还讨论了这种配体的生理相关性,这些配体仍然是辩论的常见问题,目前最好通过一部分是维生素A5发布的新型类视黄素类动物家庭的成员符合其问题。通过与其他天然的与合成配体进行比较,我们讨论了与RXR结合的配体模式中的高多样性,导致激动或拮抗谱和对允许异二聚体的特定亚型的选择性。尽管具有这种多样性,但在动物演进过程中优先保留了与引起的配体结合口袋的直接配体,其在动物演进过程中,指向其功能相关性,以及存在的存在的潜力,特异性的内源性RXR配体共享相同的功能模式。

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