Physiological role for the cochaperone FKBP52 in androgen receptor signaling

Mol Endocrinol. 2005 Jun;19(6):1654-66. doi: 10.1210/me.2005-0071. Epub 2005 Apr 14.


Molecular chaperones mediate multiple aspects of steroid receptor function, but the physiological importance of most receptor-associated cochaperones has not been determined. To help fill this gap, we targeted for disruption the mouse gene for the 52-kDa FK506 binding protein, FKBP52, a 90-kDa heat shock protein (Hsp90)-binding immunophilin found in steroid receptor complexes. A mouse line lacking FKBP52 (52KO) was generated and characterized. Male 52KO mice have several defects in reproductive tissues consistent with androgen insensitivity; among these defects are ambiguous external genitalia and dysgenic prostate. FKBP52 and androgen receptor (AR) are coexpressed in prostate epithelial cells of wild-type mice. However, FKBP52 and AR are similarly coexpressed in testis even though testis morphology and spermatogenesis in 52KO males are usually normal. Molecular studies confirm that FKBP52 is a component of AR complexes, and cellular studies in yeast and human cell models demonstrate that FKBP52 can enhance AR-mediated transactivation. AR enhancement requires FKBP52 peptidylprolyl isomerase activity as well as Hsp90-binding ability, and enhancement probably relates to an affect of FKBP52 on AR-folding pathways. In the presence of FKBP52, but not other cochaperones, the function of a minimally active AR point mutant can be dramatically restored. We conclude that FKBP52 is an AR folding factor that has critically important physiological roles in some male reproductive tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Gene Deletion
  • Genetic Vectors
  • Genotype
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Models, Molecular
  • Molecular Chaperones
  • Plasmids / metabolism
  • Point Mutation
  • Proline / chemistry
  • Prostate / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Tacrolimus Binding Proteins / genetics*
  • Tacrolimus Binding Proteins / physiology*
  • Testis / metabolism
  • Tissue Distribution
  • Transcriptional Activation


  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • Receptors, Androgen
  • Proline
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 4