Willson Timothy M, Moore John T
GlaxoSmithKline, Discovery Research, Research Triangle Park, North Carolina 27709, USA.
Mol Endocrinol. 2002 Jun;16(6):1135-44. doi: 10.1210/mend.16.6.0849.
Following the successful cloning of the orphan nuclear receptors during the 1990s we entered the 21st century with knowledge of the full complement of human nuclear receptors. Many of these proteins are ligand-activated transcription factors that act as the cognate receptors for steroid, retinoid, and thyroid hormones. In addition to these well characterized endocrine hormone receptors, there are a large number of orphan receptors of which less is known about the nature and function of their ligands. The task of deciphering the physiological function of these orphan receptors has been aided by a new generation of genomic technologies. Through application of chemical, structural, and functional genomics, several orphan nuclear receptors have emerged as pharmaceutical drug targets for the treatment of important human diseases. The significant progress that has been made in the functional analysis of more than half of the nuclear receptor gene family provides an opportunity to review the impact of genomics in this endeavor.
在20世纪90年代成功克隆出孤儿核受体之后，我们进入21世纪时已了解了人类核受体的完整组成。这些蛋白质中有许多是配体激活的转录因子，充当类固醇、视黄酸和甲状腺激素的同源受体。除了这些特征明确的内分泌激素受体外，还有大量的孤儿受体，人们对其配体的性质和功能了解较少。新一代基因组技术有助于解读这些孤儿受体的生理功能。通过化学、结构和功能基因组学的应用，几种孤儿核受体已成为治疗重要人类疾病的药物靶点。在核受体基因家族一半以上成员的功能分析方面取得的重大进展，为审视基因组学在这一努力中的影响提供了契机。
