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• W991214725 abstract "Nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that regulate gene transcription in response to their cognate ligands. The transcriptional effects of these receptors are mediated via two critical functional domains: the DNA-binding domain (DBD) and the ligand-binding domain (LBD). The DBD recognizes specific target genes, whereas the LBD modulates the gene transcription by interacting with transcriptional regulatory complexes in a ligand-dependent fashion. An important component of all signaling networks is the ability to respond to signaling molecules at physiologically relevant concentrations. In contrast to endocrine hormones that are secreted at nanomolar concentrations, intermediary metabolites are by necessity present at much higher (micromolar) concentrations. Thus, an important distinction between endocrine and metabolite/toxin-controlled receptors is that the former are high-affinity sensors, whereas the latter bind their ligands with an appropriately lower affinity. Orphan nuclear receptors provide convincing evidence that higher organisms regulate gene transcription in response to metabolic and xenobiotic cues. As metabolic disease (atherosclerosis, hypercholesterolemia, diabetes) represents the leading cause of death in industrialized societies, these receptors provide important targets for drug discovery. At the same time, discovery efforts will be enhanced by dualscreening strategies that select for therapeutic activity while minimizing interactions with xenobiotic receptors. Finally,orphan receptors represent a valuable source for future exploration because 26 orphans have yet to be associated with specific ligands." @default.
• W991214725 created "2016-06-24" @default.
• W991214725 creator A5038335713 @default.
• W991214725 date "2003-01-01" @default.
• W991214725 modified "2023-09-23" @default.
• W991214725 title "Orphan Nuclear Receptors" @default.
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• W991214725 doi "https://doi.org/10.1016/b978-012124546-7/50639-2" @default.
• W991214725 hasPublicationYear "2003" @default.
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