Modulation of xenobiotic receptors by steroids.
Modulation of xenobiotic receptors by steroids.
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DOI：
10.3390/molecules18077389
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发表时间：
2013-06-24
期刊：
影响因子：
--
通讯作者：
Chen T
中科院分区：
文献类型：
--
作者：
Banerjee M;Robbins D;Chen T
核受体（Nuclear receptor，NRs）是一种配体激活的转录因子，调节靶基因的表达。NR在许多人类疾病中起重要作用，包括代谢疾病和癌症，因此是一类关键的治疗靶点。类固醇在调节核受体中发挥重要作用;除了作为类固醇受体的配体，类固醇（及其代谢物）还调节其他NR，如甾烷X受体和组成型雄烷受体（称为异生素受体），它们参与类固醇代谢。异源生物素受体具有混杂的配体结合特性，其结构多样的配体包括类固醇及其代谢物。因此，类固醇、其代谢和代谢物、异生物质受体、类固醇受体以及它们调节的各自的信号传导途径具有功能性相互作用。本文综述了这些功能的相互作用和它们的影响，类固醇受体和异生素受体介导的活动，重点是类固醇调节途径，涉及的甾烷X受体和组成型雄烷受体。综述的重点是与甾体配体结合的外源性受体的结构-功能研究。
Nuclear receptors (NRs) are ligand-activated transcription factors that regulate the expression of their target genes. NRs play important roles in many human diseases, including metabolic diseases and cancer, and are therefore a key class of therapeutic targets. Steroids play important roles in regulating nuclear receptors; in addition to being ligands of steroid receptors, steroids (and their metabolites) also regulate other NRs, such as the pregnane X receptor and constitutive androstane receptor (termed xenobiotic receptors), which participate in steroid metabolism. Xenobiotic receptors have promiscuous ligand-binding properties, and their structurally diverse ligands include steroids and their metabolites. Therefore, steroids, their metabolism and metabolites, xenobiotic receptors, steroid receptors, and the respective signaling pathways they regulate have functional interactions. This review discusses these functional interactions and their implications for activities mediated by steroid receptors and xenobiotic receptors, focusing on steroids that modulate pathways involving the pregnane X receptor and constitutive androstane receptor. The emphasis of the review is on structure-function studies of xenobiotic receptors bound to steroid ligands.
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