A functional genetic screen to identify factors involved in glucocorticoid receptor (GR) transactivation

GR is a ligand-modulated transcription factor and is activated upon binding of glucocorticoids (GCs) in various tissues. It plays a central role in many physiological processes e.g. in regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Although several aspects of GC signalling are known, many steps are still to be elucidated. The aim of this study is to undertake a screen to find novel factors involved in the GC signalling pathway. We have created a stable cell line which dies in response to GCs. These cells were randomly mutated and selected in medium containing GCs. Thus, only cells which are not responsive to GCs anymore could survive the selection. In one of the resistant clones we have looked for mutated genes which might cause the resistance. We are now looking at the involvement of the identified factors in GR signalling. With this approach, we hope to shed new light on the functioning of GR.