PDF(Pubmed)
Abstract：
Nuclear hormone receptors (NHRs) are a family of ligand-regulated transcription factors that control key aspects of development and physiology. The regulation of NHRs by ligands derived from metabolism or diet makes them excellent pharmacological targets, and the mechanistic understanding of how NHRs interact with their ligands to regulate downstream gene networks, along with the identification of ligands for orphan NHRs, could enable innovative approaches for cellular engineering, disease modeling and regenerative medicine. We review recent discoveries in the identification of physiologic ligands for NHRs. We propose new models of ligand-receptor co-evolution, the emergence of hormonal function and models of regulation of NHR specificity and activity via one-ligand and two-ligand models as well as feedback loops. Lastly, we discuss limitations on the processes for the identification of physiologic NHR ligands and emerging new methodologies that could be used to identify the natural ligands for the remaining 17 orphan NHRs in the human genome.
摘要：
核激素受体（NHR）是一组配体调节的转录因子，可控制发育和生理的关键方面。来自代谢或饮食的配体对NHRs的调节使其成为优异的药理学靶标，以及对NHRs如何与其配体相互作用以调节下游基因网络的机械理解，随着孤儿NHR配体的鉴定，可以实现细胞工程的创新方法，疾病建模和再生医学。我们回顾了最近在鉴定NHR生理配体方面的发现。我们提出了配体-受体共同进化的新模型，激素功能的出现以及通过单配体和双配体模型以及反馈回路调节NHR特异性和活性的模型。最后,我们讨论了生理NHR配体鉴定过程的局限性，以及可用于鉴定人类基因组中剩余17个孤儿NHR的天然配体的新兴方法。
