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

Stubsrud, Elisabeth (2005-12)

Thesis (MSc (Biochemistry))--University of Stellenbosch, 2005.


Endogenous glucocorticoids (GCs) modulate many physiological functions in the human body 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 is associated with severe side-effects. GCs mediate their effects through the ligand-dependent transcription factor, the glucocorticoid receptor (GR), either by causing an increase (transactivation) or a decrease (transrepression) in gene transcription. The bioactivity of a ligand in GR-mediated transcriptional regulation is established by a transcriptional doseresponse curve, where the potency (EC50 value) and the efficacy (maximal response) of the ligand are determined. A central question is how different GR ligands elicit their differential physiological responses for the same gene in the same cell. The main aim of this thesis is to investigate if the phosphorylation of GR at serine 211 (Ser211) correlates with the potency and/or efficacy of a particular ligand in transactivation and transrepression of gene expression.

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