A Compendium of Nuclear Receptors: The Superfamily of Ligand-Modulated Transcription Factors

Abstract

The ‘Nuclear Receptor Super-family’ is a group of ligand-modulated transcription factors with 48 members identified in human genome. Members of this family of receptors are now established to be involved in regulation of a plethora of physiological processes in the paradigms of development, reproduction, metabolism and homeostasis. Also, in the myriads of patho-physiological processes, these receptors have consistently exhibited enormous potential as targets for the treatment of diseases such as cancers, osteoporosis, diabetes, obesity, coronary heart disease, asthma, hypertension, thyroid conditions and multiple other metabolic disorders. In recent times, it is estimated that about 15% of the clinical drugs, used in treatments of different ailments, target nuclear receptors. These receptors include steroid/thyroid hormone receptors and orphan/adopted receptors that function as intra-cellular transcription factors to regulate expression of several hundreds of genes in response to their cognate ligands. Interestingly, nuclear receptors are also being assigned a novel role in serving as ‘epigenetic marks’ for the retention and transmission of cellular ‘transcriptional memory’. These receptors function primarily either as homodimers or heterodimers with Retinoid X Receptor (RXR) or sometimes as monomers. Being ‘drug responsive’ these receptors offer attractive targets for drug discovery since their activities can be favorably modulated by interacting ligands. However, many of the newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological roles and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of action. It has been well-over three decades since the cloning of steroid/nuclear receptors in the 1980s. Therefore, it’s only appropriate to prepare a comprehensive review that provides a compendium of facts and events from receptor cloning and characterization to establishment of receptor domain structures, physiological functioning and consequences of receptor malfunctioning. This review is expected to serve as a refreshing compendium of nuclear receptors for both, the beginners, as well as experts working in the areas of nuclear receptor biology.