FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications.

Psychotropic medications target glycogen synthase kinase 3β (GSK3β), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3β at serine 9 (pGSK3β(S9)). FKBP51 associates with GSK3β mainly through its FK1 domain; furthermore, it also changes GSK3β's heterocomplex assembly by associating with the phosphatase PP2A and the kinase cyclin-dependent kinase 5.

Association of FKBP51 with priming of autophagy pathways and mediation of antidepressant treatment response: evidence in cells, mice, and humans.

Background: FK506 binding protein 51 (FKBP51) is an Hsp90 co-chaperone and regulator of the glucocorticoid receptor, and consequently of stress physiology. Clinical studies suggest a genetic link between FKBP51 and antidepressant response in mood disorders; however, the underlying mechanisms remain elusive. The objective of this study was to elucidate the role of FKBP51 in the actions of antidepressants, with a particular focus on pathways of autophagy.

Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.

Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the androgen receptor (AR).

Increased glyoxalase-1 levels in Fkbp5 knockout mice caused by glyoxalase-1 gene duplication.

Fkbp5 is genetically linked to stress-related diseases. Fkbp5 knockout mice are available and widely used to explore the role of Fkbp5 in health and disease. We found that these mice carry a gene duplication of glyoxylase-1, which explains why glyoxylase-1 levels are increased in the Fkbp5 knockout mice.