Noy Noa
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4965, USA.
Biochemistry. 2007 Nov 27;46(47):13461-7. doi: 10.1021/bi7018699. Epub 2007 Nov 6.
The superfamily of nuclear hormone receptors includes transcription factors that play key roles in regulating multiple biological functions during embryonic development and in adult tissues, as well as in many disease states. The quintessential characteristic of nuclear receptors, and the basis for the name of the family, is that their transcriptional activities can be regulated by small molecules, usually comprised of hydrophobic compounds. However, the endogenous ligands for approximately half of the members of the nuclear receptor family are unknown, and these receptors are thus designated as "orphan receptors". One class of orphan receptors encompasses receptors that display a broad ligand selectivity; i.e., they can promiscuously bind to and may be activated by multiple ligands. This characteristic complicates the identification of physiologically meaningful ligands that activate these receptors in vivo. Here, we discuss a few examples of promiscuous receptors and outline strategies that may be employed in shedding light on the nature of bona fide ligands for such receptors.
核激素受体超家族包括转录因子，这些转录因子在胚胎发育过程中以及成年组织中，乃至在许多疾病状态下，对调节多种生物学功能起着关键作用。核受体的典型特征，也是该家族名称的由来，是它们的转录活性可由小分子调节，这些小分子通常由疏水化合物组成。然而，核受体家族中约一半成员的内源性配体尚不清楚，因此这些受体被称为“孤儿受体”。一类孤儿受体包括具有广泛配体选择性的受体；也就是说，它们可以杂乱地结合多种配体并可能被其激活。这一特性使得鉴定在体内激活这些受体的具有生理意义的配体变得复杂。在这里，我们讨论一些具有杂乱配体选择性的受体的例子，并概述为阐明此类受体的真正配体性质可能采用的策略。
