The DOI matches its Crossref record; 44 of the 49 references it cites were found in a registry or an index.
Physiological Role for the Cochaperone FKBP52 in Androgen Receptor Signaling
Open accessAbstract
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.
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In the citing paper
“While FKBP52 is known to functionally interact with AR, GR and PR [6–8], β-catenin only interacts strongly with AR, but not GR and PR [20].”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“FKBP52 knockout mice have developmental defects in reproductive tissues (in males) consistent with reduced ARsignaling and a failure of embryo implantation (in females) consistent with reduced PR signaling (4, 37).”
From FKBP51 Promotes Assembly of the Hsp90 Chaperone Complex and Regulates Androgen Receptor Signaling in Prostate Cancer Cells (2010) · cites this paper as [4]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Because the FKBP51 knockout mouse does not display overt defects in androgen signaling (4, 37), the contribution of FKBP51 to AR function has been unclear.”
From FKBP51 Promotes Assembly of the Hsp90 Chaperone Complex and Regulates Androgen Receptor Signaling in Prostate Cancer Cells (2010) · cites this paper as [4]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This is despite the fact that FKBP51 is not required for AR function in the development of the male mouse reproductive system, which instead relies on the closely related cochaperone FKBP52 (4, 37).”
From FKBP51 Promotes Assembly of the Hsp90 Chaperone Complex and Regulates Androgen Receptor Signaling in Prostate Cancer Cells (2010) · cites this paper as [4]
Experimental — accuracy not yet measuredIn the citing paper
“FKBP52 is a positive regulator of glucocorticoid receptor (GR) [5], progesterone receptor (PR) [6], and androgen receptor (AR) [7], but not estrogen receptor (ER) or mineralocorticoid receptor (MR) [5].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [7]
In the citing paper
“Male 52KO mice display phenotypes consistent with partial androgen insensitivity including dysgenic prostate and seminal vesicles, ambiguous external genitalia including hypospadias, and retention of nipples into adulthood [7, 32].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [7]
In the citing paper
“Given the androgen, progesterone and glucocorticoid insensitivity phenotypes observed in the fkbp52-deficient mice [6, 7, 32, 35, 51], FKBP52 is likely to have an important role and to serve as a therapeutic target in a variety of diseases that are dependent on these hormone signaling pathways.”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [7]
In the citing paper
“Our laboratory (Yong et al., 2007) and others (Cheung-Flynn et al., 2005) have shown that male mice with targeted ablation of FKBP52 are infertile due to a developmental defect of the penis termed hypospadias – a condition prevalent in newborn boys and thought to arise from androgen insensitivity (Batch et al., 1992; Nakao et al., 1992).”
From FKBP51 and Cyp40 are positive regulators of androgen-dependent prostate cancer cell growth and the targets of FK506 and cyclosporin A (2010) · cites this paper as Cheung-Flynn et al., 2005
In the citing paper
“suggesting that FKBP52 is an essential immunophilin controlling AR activity in these tissues.”
From The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms (2007) · cites this paper as [12]
In the citing paper
“Moreover, only select ARcontrolled tissues were affected in male FKBP52 KO animals, most notably the prostate gland.”
From The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms (2007) · cites this paper as [12]
In the citing paper
“Interestingly, FKBP52KO males also showed prostate dysgenesis, as well as dramatically reduced AR activity at both endogenous and heterologous genes (12,39).”
From The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms (2007) · cites this paper as [12]
In the citing paper
“In this case, loss of FKBP52 caused male infertility through a selective abrogation of AR activity, while apparently leaving all other steroid receptor processes in the male unchanged.”
From The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms (2007) · cites this paper as [12]
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Citations
Cites
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“First, an established yeast model for steroid receptor function (19, 20) was employed to take advantage of the fact that Saccharomyces cerevisiae lacks an endogenous gene for the TPR-containing FKBP family members.”
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The Hsp90‐binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo
Riggs, D. L., Roberts, P. J., Chirillo, S. C., Cheung‐Flynn, J., Prapapanich, V., Ratajczak, T., Gaber, R., Picard, D., & Smith, D. F. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg108 · Cited by 353 · cited 8×
“Furthermore, a double point mutation (52-FD67DV) in the PPIase active site (20) also blocks potentiation, suggesting that the PPIase domain is required for enhancing AR function.”
BackgroundMethodResultInfluentialSelf-citationAhmed, S. F., Cheng, A. W.-F., Dovey, L., Hawkins, J. R., Martin, H., Rowland, J., Shimura, N., Tait, A. D., & Hughes, I. A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.2.6337 · Cited by 315
Flagged first, then by citations
5 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Alberti, 2003, BAG-1—a nucleotide exchange factor of Hsc70 with multiple cellular functions., Cell Stress Chaperones, 8, 225, 10.1379/1466-1268(2003)008<0225:BNEFOH>2.0.CO;2 · DOI
- McDonough, 2003, CHIP: a link between the chaperone and proteasome systems., Cell Stress Chaperones, 8, 303, 10.1379/1466-1268(2003)008<0303:CALBTC>2.0.CO;2 · DOI
Cited by
Sorted by citations
Items 201–215 of 215
FKBP52-Progesterone Receptor Signaling During Pregnancy
Tranguch, S. L. (2007)
Bostanthirige, D. H., Komaragiri, S. K., Joshi, J., Al-Zahrani, M., Saini, I., Jain, S. R., Bowen, N. J., Havrda, M. C., & Chaudhary, J. (2021) · Oncoscience · doi:10.18632/oncoscience.524
Ilaslan, E., Markosyan, R., Sproll, P., Bj, S., Sajek, M. P., Sajek, M. P., Hayrapetyan, H., Sarkisian, T., Лившиц, Л. А., Nef, S., et al. (2021) · Yearbook of pediatric endocrinology · doi:10.1530/ey.18.6.3
Chaperones and ADP-Ribosylating Bacterial Toxins
Barth, H., & Ernst, K. (2018) · Toxinology · doi:10.1007/978-94-007-6449-1_7
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Data from Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer
Ostrow, K. L., Park, H. L., Hoque, M. O., Kim, M. S., Liu, J., Argani, P., Westra, W. H., Criekinge, W. V., & Sidransky, D. (2023) · doi:10.1158/1078-0432.c.6517723
Chen, J., Wang, Y., Wu, X., Zhang, C., Miao, D., Wang, Y., Yang, H., & Wang, Z. (2025) · British Poultry Science · doi:10.1080/00071668.2025.2518608
Dual proximity-based interactome mapping of FKBP51 and FKBP52 uncovers shared metabolic networks
Hill, S. E., Parikh, P., Gebru, N. T., Banjade, S., Guergues, J., Wohlfahrt, J., Stevens, S. M., & Blair, L. J. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153968
Investigating the role of FKBP4 in testis germ cell tumor via integrated in silico approach
Sahni, D., Kumar, B., Porwal, S., Arya, A. K., Akhtar, M. S., & Bharati, A. P. (2026) · In Silico Pharmacology · doi:10.1007/s40203-026-00592-w
BindingDB Entry 50046680: Structure-Affinity Relationship Analysis of Selective FKBP51 Ligands.
BindingDB (2016) · UC San Diego · doi:10.7270/q25q4xwr
BindingDB Entry 50008490: A Novel Decalin-Based Bicyclic Scaffold for FKBP51-Selective Ligands.
BindingDB (2021) · UC San Diego · doi:10.7270/q2q52t10
Metadata
- Authors
- Cheung-Flynn, J., Prapapanich, V., Cox, M. B., Riggs, D. L., Suarez-Quian, C., & Smith, D. F.
- Affiliations
- Department of Biochemistry and Molecular Biology (J.C.-F., V.P., M.B.C., D.L.R., D.F.S.), Mayo Clinic College of Medicine, Scottsdale, Arizona 85259
- Mayo Clinic (US)
- Department of Cell Biology (C.S.-Q.), Georgetown University Medical Center, Washington, D.C. 20057
- Corresponding author
- Smith, David F.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-06-01
- Volume
- 19
- Issue
- 6
- Pages
- 1654-1666
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2109243666
- Cited by
- 212
- References
- 49
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 13 · 2013: 15 · 2012: 20
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Nebraska Medical Center
- Mayo Foundation for Medical Education and Research
- National Institutes of Health
- U.S. Public Health Service (R01-48218)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- FKBP52, androgen receptor, co-chaperones, immunophilins, peptidylprolyl isomerase, steroid receptor signaling, androgen insensitivity syndrome, ambiguous genitalia, receptor folding, transcriptional activation
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Genetic Vectors, Genotype, Humans, Immunohistochemistry, Male, Models, Genetic, Models, Molecular, Plasmids, Proline, Prostate, Protein Binding, Protein Conformation, Receptors, Androgen, Testis, Tissue Distribution, Blotting, Western, Signal Transduction, Transcriptional Activation, Gene Deletion, Point Mutation, Protein Structure, Tertiary, Protein Folding, Mice, Knockout, Molecular Chaperones, HSP90 Heat-Shock Proteins, Tacrolimus Binding Proteins, Mice
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