Fig. 2. Chaperone cycle.

A) Upon dissociation from regulatory elements, GR will either re-enter the chromatin cycle or lose its hormone. Hormone–free GR is incapable of binding hormone on its own, and regains its hormone-binding affinity only after association with nuclear chaperone machinery. B) In the absence of hormone, GR association with chaperone machinery protects it from proteasome-mediated degradation. Chaperone cycle and proteasome machinery recycle or degrade GR molecules, respectively, serving as a GR quality control system.