An investigation of the role of phosphorylation at Ser211 of the glucocorticoid receptor in ligand-specific transcriptional regulation

[摘要] Endogenous glucocorticoids (GCs) modulate many physiological functions in the humanbody and synthetic GCs are the most effective therapy in the treatment of inflammation,autoimmune and endocrine disorders. However, the long-term usage of synthetic GCs isassociated with severe side-effects. GCs mediate their effects through the ligand-dependenttranscription factor, the glucocorticoid receptor (GR), either by causing an increase(transactivation) or a decrease (transrepression) in gene transcription. The bioactivity of aligand in GR-mediated transcriptional regulation is established by a transcriptional doseresponsecurve, where the potency (EC50 value) and the efficacy (maximal response) of theligand are determined. A central question is how different GR ligands elicit their differentialphysiological responses for the same gene in the same cell. The main aim of this thesis is toinvestigate if the phosphorylation of GR at serine 211 (Ser211) correlates with the potencyand/or efficacy of a particular ligand in transactivation and transrepression of gene expression.

[发布机构] Stellenbosch University