Figure 2

Schematic model of FKBP5 functions involved in several different signalling pathways, including glucocorticoid receptor (GR) signalling pathways (A), as well as NF-κB (B) and AKT–PHLPP (C) pathways. (A) In the absence of dexamethasone, FKBP5 is the primary immunophilin of the FKBP–Hsp90–GR complex in an inactive stable state. Upon dexamethasone binding, FKBP5 is displaced by FKBP4, and the complex can enter the nucleus. The complex then dissociates, allowing binding of GR to DNA-binding motifs of target genes, leading to apoptosis. (B) In the presence of doxorubicin or damage from radiation, FKBP5 might involve in the control of IKKα activity, which can induce IκBα degradation via its phosphorylation, nuclear translocation, and activation of NF-κB, and the expression of its target genes, consequently triggering cell apoptosis. (C) FK506 binding protein 5 interacts with PHLPP and AKT, acting as a scaffolding protein that promotes the interaction between AKT and PHLPP, thereby enhancing the dephosphorylation of AKT and inactivating AKT, which results in the blockade of AKT signalling for cell survival and leads to cell apoptosis or death.