title: Comprehensive overview of the structure and regulation of the glucocorticoid receptor.
abstract: Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.
authors.affiliation: Inflammation Research Center (S.V., L.D., C.L.), Flanders Institute for Biotechnology, B9052 Ghent, Belgium; and Department of Biomedical Molecular Biology (S.V., L.D., C.L.), Ghent University, B9052 Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Vandevyver
authors.forename: Lien
authors.initials: L
authors.lastname: Dejager
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D035683:MicroRNAs; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid