Overview of Nomenclature of Nuclear Receptors

Abstract

Abstract--Nuclear receptor pharmacology has, to a certain extent, led the way, compared with other receptor systems, in the appreciation that ligands may exert very diverse pharmacology, based on their individual chemical structure and the allosteric changes induced in the receptor/accessory protein complex. This can lead to very selective pharmacological effects, which may not necessarily be predicted from the experience with other agonists/partial agonists/antagonists. If this is the case, then drug discovery may be back to drug-specific pharmacology (where each drug may have an original profile), rather than specificdrug pharmacology (where agents specific for a receptor have a distinct profile). As functional selectivity is indeed a crucial mechanism to be considered when going through the drug discovery development process, then initial screens using reconstituted systems may not show the appropriate pharmacology, simply because the required stoichiometry of corepressors and coactivators may not be present to select the best compounds; therefore, multiple effector systems are necessary to screen for differential activation, and, even then, screening with in vivo pathophysiological models may ultimately be required for the selection process-a massive but necessary task for pharmacologists. Thus, the characterization of nuclear receptors and their associated proteins and the ligands that interact with them will remain a challenge to pharmacologists.

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

“…Increasing evidence suggests that the cone gradients are generated during development by the action of diffusible growth factors or hormones (extrinsic signals) and their receptors, mainly nuclear receptor family transcription factors (intrinsic program). These receptors exist as families of related genes that have apparently diverged from a common ancestral precursor (Germain et al, 2006). In the following section, we will focus on recent progress on the role of nuclear receptors in cone development and discuss the possible action of their ligands.…”

“…Findings from a study designed to map expression quantitative trait loci (eQTL) in the rat showed that point mutations affecting a conserved serine and another residue in the N-terminal domain of Trβ2 (Ser56Asn and His58Arg) correlated with decreases in S-opsin expression levels of as much as 30% in homozygotes (Scheetz et al, 2006). The affected residues fall within a poorly characterized ligand-independent transactivation domain that can interact with cofactors and is the target of post-translational modification in some nuclear receptors (Germain et al, 2006). Trβ2 binds directly to the S-opsin promoter (Figure 3) and has been reported to interact with the basal transcription machinery as well as co-activators and co-repressors to exert complex regulatory effects on target genes (Eckey et al, 2003).…”

The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases

“…So far, 18, 49, and 48 NRs in six subfamilies have been identified in Drosophila melanogaster, mice, and humans, respectively [2][3][4]. TLX, also known as NR2E1 (nuclear receptor subfamily 2, group E, member 1), encodes an orphan NR with no identified ligand.…”

The history of a developmental stage: Metamorphosis in chordates

“…TR is a TH-regulated transcription factor that belongs to the superfamily of nuclear receptors that plays a central role in various physiological processes as diverse as reproduction, development, and the control of homeostasis (Germain et al, 2006;Gronemeyer et al, 2004;Laudet and Gronemeyer, 2005). In the absence of ligand, the receptor is located on specific response elements in the regulatory regions of target genes and actively inhibits transcription.…”