Hsp90 is crucial to cellular signaling by its regulation of the folding, activity, and stability of a wide range of client proteins. These client protein complexes may also contain one or more cochaperones (1). One class of Hsp90-binding cochaperone is composed of proteins with a characteristic tetratricopeptide repeat (TPR) domain that forms an Hsp90 binding site. Among the TPR cochaperones of Hsp90 are Hop/Sti1, protein phosphatase PP5, and members of both the FK506- and cyclosporin A-binding families of immunophilins (2).
FK506-binding protein 51 (FKBP51) and FKBP52 are large molecular weight immunophilins that are part of the mature glucocorticoid receptor (GR) heterocomplex (3).
The N terminal domain of each protein binds FK506 and has peptidyl-prolyl isomerase (PPIase) activity that converts prolyl peptide bonds within target proteins from cis- to trans- proline. The C-terminal domains contain the TPR repeats involved in protein-protein interactions with the Hsp90 (4). Although FKBP52 and FKBP51 share ~75% sequence similarity, they affect hormone binding by glucocorticoid receptor in opposing manners and have different Hsp90-binding characteristics (3).
FK506 binding protein 51 kDa (FKBP51 or otherwise referred to as FKBP54) has been identified as a progestininducible gene. This protein is predominantly expressed in murine T cells but in humans, it is abundantly expressed in numerous tissues at levels many times higher than FKBP12. The FKBP51 gene is known to be induced by glucocorticoids (5).