Molecular basis for the regulation of the nuclear receptor LRH-1
Molecular basis for the regulation of the nuclear receptor LRH-1
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DOI：
10.1016/j.ceb.2014.10.007
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发表时间：
2015-04-01
影响因子：
7.5
通讯作者：
Schoonjans, Kristina
中科院分区：
文献类型：
--
作者：
Stein, Sokrates;Schoonjans, Kristina
肝受体同源物-1 （Liver receptor homology -1, LRH-1）是一种具有多种发育、分化和代谢功能的核受体，在肠肝系统中被广泛研究。虽然最初被描述为孤儿NR，但最近的研究表明，特定的磷脂可作为内源性LRH-1配体。尽管配体的结合可以增强其转录激活，但翻译后修饰（PTMs）和协同调节因子和其他nr的结合已成为微调LRH-1靶基因选择性调控的机制。在这篇综述文章中，我们将讨论LRH-1是如何通过ptm和配体和共调节剂的结合来调节的，并特别关注肝脏生理学来解释一些代谢后果。
Liver receptor homolog-1 (LRH-1) is a nuclear receptor (NR) with diverse functions in development, differentiation and metabolism and has been extensively studied in the enterohepatic system. While initially described as an orphan NR, recent studies suggest that specific phospholipids act as endogenous LRH-1 ligands. Although binding of ligands may enhance its transcriptional activation, posttranslational modifications (PTMs) and binding of coregulators and other NRs have emerged as mechanisms to fine-tune the selective regulation of LRH-1 target genes. In this review article, we will discuss how LRH-1 is regulated by PTMs and binding of ligands and coregulators, and explain some metabolic consequences with a special focus on liver physiology.