Twenty years of nuclear receptors

Abstract

This EMBO Conference on ‘Nuclear Receptors: from Chromatin to Disease’ took place between 29 September and 1 October 2005, in Gardone Riviera, Italy, and was organized by A. Maggi, J. Schwabe, D. Moore and T. Perlmann. ![][1] Nuclear receptors are a family of transcription factors the activity of which is modulated by binding to small signalling molecules. These compounds trigger changes in the conformational and dynamic behaviour of the receptors, which in turn regulate the recruitment of co‐regulators and chromatin‐modifying machineries. Nuclear receptors regulate growth, development and metabolic homeostasis in multicellular organisms in which hormones and non‐hormonal substances, such as intracrine regulatory metabolites, signal the status of the organism as a whole. Several synthetic ligands can specifically modulate the communication of a nuclear receptor with its cellular environment. Lipid‐soluble hormones and vitamins can pass easily through the lipid bilayer of cell membranes, triggering an intercellular communication network in which nuclear receptors exert genomic and non‐genomic actions that are determined by the specific recognition of the ligand. Nuclear receptors are one of the main classes of transcriptional regulators in metazoans—there are 48 in humans—and they first appeared in the earliest stages of animal evolution, long before the divergence of vertebrates and invertebrates. Steroid receptors were first identified biochemically in the 1960s (Jensen, 2004), but nuclear receptors were only recognized as a superfamily of transcription factors 20 years ago (Green et al , 1986; Hollenberg et al , 1985; Miesfeld et al , 1986). The family includes disguised ‘orphan receptors’, which are awaiting ligand identification, and true orphans, which regulate transcription independently of ligand binding. Today, the nuclear receptor field has broadened dramatically and covers areas ranging from structural and functional analyses of the molecular mechanisms of transcription regulation to nuclear‐receptor‐based drug design and (pre)clinical studies aimed at exploiting the potential of these master … [1]: /embed/graphic-1.gif