Biased regulation of glucocorticoid receptors signaling - 13/08/23
, Jingyu Chen ⁎ Abstract |
Glucocorticoids (GCs), steroid hormones that depend on glucocorticoid receptor (GR) binding for their action, are essential for regulating numerous homeostatic functions in the body.GR signals are biased, that is, GR signals are various in different tissue cells, disease states and ligands. This biased regulation of GR signaling appears to depend on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly (recruitment of co-regulators) and intercellular differences. Based on the bias regulation of GR, selective GR agonists and modulators (SEGRAMs) were developed to bias therapeutic outcomes toward expected outcomes (e.g., anti-inflammation and immunoregulation) by influencing GR-mediated gene expression. This paper provides a review of the bias regulation and mechanism of GR and the research progress of drugs.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | GR signaling is biased in different cells, tissues and disease states. |
• | The bias signal of GR is associated with ligands, PTMs, and coregulator recruitment. |
• | GCs drugs with good efficacy but low ADR can be developed by the bias signal of GR. |
Chemical compounds studied in this article : GW870086 (PubChem CID: 11376392), ZK245186 (PubChem CID: 24795088), AZD9567 (PubChem CID: 121248172), Fosdagrocorat (PubChem CID: 24872952), BI653048 (PubChem CID: 44543970), C108297 (PubChem CID: 25110774), ORG 214007–0 (PubChem CID: 154659439), LEO 134310 (PubChem CID: 126714060), GSK866 (PubChem CID: 25058139), ZK216348 (PubChem CID: 9805004), CpdA (PubChem CID: 9838148), AL438 (PubChem CID: 9906282), RU24858 (PubChem CID: 223258861), RU24782 (PubChem CID: 385448896)
Abbreviations : GCs, GR, ADR, SEGRAMs, PTMs, RA, MAPK, DUSP1, MKP1, GRE, DBD, SMRT, NcoR, HDACs, SRC-1, CBP, IκB, GILZ, NTD, LBD, AF1 2, P, GRIP-1, JNK, CDK, MAPK, GSK-3β
Keywords : Glucocorticoid receptor, Biased regulation, Selective glucocorticoid receptor modulators, Selective glucocorticoid receptor agonists
Plan
Vol 165
Article 115145- septembre 2023 Retour au numéro
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