Glucocorticoid Receptor (GFP-GR) reporter cell line
Nuclear hormone receptors (NHRs) are a superfamily of transcription factors that function as powerful metabolic regulators to control a variety of systemic processes in physiology. They also play key roles in the pathophysiology of many major disease states, such as diabetes, obesity, inflammation, atherosclerosis and heart failure. To date, this superfamily has provided a rich source of drug design targets and it is continuing to be one of the hottest areas for pharmaceutical research.
Glucocorticoids (GCs) are steroid hormones that allow us to cope with environmental and physiological stresses. Although GCs are widely used as anti-inflammatory agents in several clinical areas, long-term use of those steroids causes problems instead. Full achievement of the clinical potential of GCs necessitates limiting the side effects of these drugs.
The lipophilic nature of GCs allows them to readily diffuse into the cells, where they bind to a cytosolic receptor, the Glucocorticoid Recetpor (GR) to exert their mechanism of action. Without ligand binding, GR is predominantly localized in cytoplasm, whereas upon ligand binding it rapidly translocates to nucleus where it can both positively and negatively regulate gene expression. GR belongs to the nuclear receptor superfamily of ligand-activated transcription factors that function as powerful metabolic regulators.
The GFP-GR reporter cell line was created by stable transfection of HEK293 cells with a plasmid (with neomycin resistant gene) expressing GFP-GR fusion protein. This reporter cell line is an ideal tool for screening small molecules that specifically target GR nuclear translocation and GR stability.