fig1

Figure 1. Mechanisms of GR action upon GC stimulation. Upon glucocorticoid (GC) binding, the cytoplasmic glucocorticoid receptor (GR), in complex with accessory proteins Hsp90, p23 and FKBP51, undergoes a conformational change and interacts with FKBP52. This results in dissociation of the multiprotein complex and facilitates subsequent GR signaling. The classical pathway involves genomic mechanisms of gene regulation by GR, while the non-classical pathway results in: a) inner membrane localization of GR, which can lead to ERK1/2 and RhoA activation; b) translocation of GR to mitochondria where it results in inhibition of apoptosis in GC-sensitive cells. Nuclear translocation of GR enhances or represses transcription of target genes by c) direct binding to glucocorticoid responsive element (GRE) or negative GRE (nGRE) sites; d) tethering to other transcription factors without direct GRE interaction; e) or in a composite manner, which involves adjacent GRE binding