The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
The Hsp90‐binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo
Open accessAbstract
Hsp90 is required for the normal activity of steroid receptors, and in steroid receptor complexes it is typically bound to one of the immunophilin-related co-chaperones: the peptidylprolyl isomerases FKBP51, FKBP52 or CyP40, or the protein phosphatase PP5. The physiological roles of the immunophilins in regulating steroid receptor function have not been well defined, and so we examined in vivo the influences of immunophilins on hormone-dependent gene activation in the Saccharomyces cerevisiae model for glucocorticoid receptor (GR) function. FKBP52 selectively potentiates hormone-dependent reporter gene activation by as much as 20-fold at limiting hormone concentrations, and this potentiation is readily blocked by co-expression of the closely related FKBP51. The mechanism for potentiation is an increase in GR hormone-binding affinity that requires both the Hsp90-binding ability and the prolyl isomerase activity of FKBP52.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“Previous studies in yeast demonstrated that FKBP52 binding to Hsp90 is required for regulation of AR activity [7].”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [7]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“In contrast, FKBP52 enhances GR, PR, and AR responsiveness to cognate hormone (28).”
From FKBP51 Promotes Assembly of the Hsp90 Chaperone Complex and Regulates Androgen Receptor Signaling in Prostate Cancer Cells (2010) · cites this paper as [28]
Checked by a reasoning model — may be wrong.
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
“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 [7]
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
“FKBP51 inhibits GR ligand binding, nuclear translocation and transcriptional activity, while FKBP52 potentiates each of these fundamental GR activities22–32.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [23]
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
“unlike FKBP52, FKBP51 does not enhance GR ligand binding in vitro, consistent with in vivo studies23,27,29.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [23]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus, the relative concentrations of FKBP51 and FKBP52 in the cell dictate the level of GR activity in vivo23,28,55.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [23]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The co-expression of FKBP52 (K354A), which completely lacks Hsp90 binding [7], with β-catenin (S33A) also resulted in the synergistic up-regulation of AR-mediated luciferase reporter expression comparable to that observed with wild type FKBP52 both in the presence and absence of hormone (Fig 5B).”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“However, FKBP51 does not potentiate GR ligand binding in any of these conditions, unlike FKBP52, recapitulating in vivo findings23,29.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“strongly suggesting FKBP52 potentiates the GR ligand binding affinity beyond the minimal chaperone mixture, consistent with reports in vivo23.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [23]
In 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 [5]
In the citing paper
“The fact that FKBP52 regulation has been localized to the receptor ligand binding domain (LBD) [5, 15] suggests that the FK1 interaction partner is the receptor LBD.”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [5]
In the citing paper
“The FK1 domain facilitates binding to the immunosuppressive drug FK506, confers PPIase activity [3], and is the primary regulatory domain for SHRs [5].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [5]
In the citing paper
“The FKBPs compete for binding to the SHR complex and, as a result, overexpression of FKBP51 decreases receptor regulation by FKBP52 [5]”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [5]
In the citing paper
“The FK1 domain is deemed critical for receptor potentiation by FKBP52 [5], but its enzymatic activity is not required for this potentiation. Domain integrity in and around the PPIase pocket is essential [9].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mumberg, D., Müller, R., & Funk, M. (1995) · Gene · doi:10.1016/0378-1119(95)00037-7 · Cited by 1,972
Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones*
Pratt, W. B., & Toft, D. O. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0303 · Cited by 1,791
Bunone, G., Briand, P.-A., Miksicek, R. J., & Picard, D. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00571.x · Cited by 985
Self-citationReduced levels of hsp90 compromise steroid receptor action in vivo
Picard, D., Khursheed, B., Garabedian, M. J., Fortin, M. G., Lindquist, S., & Yamamoto, K. R. (1990) · Nature · doi:10.1038/348166a0 · Cited by 787
Self-citationSteroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones
Pratt, W. B. (1997) · Endocrine Reviews · doi:10.1210/er.18.3.306 · Cited by 641
Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)‐domain co‐chaperones
Prodromou, C., Siligardi, G., O’Brien, R., Woolfson, D. N., Regan, L., Panaretou, B., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.754 · Cited by 427
Ma, Q., & Whitlock, J. P. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.14.8878 · Cited by 426
Mutational Analysis of Hsp90 Function: Interactions with a Steroid Receptor and a Protein Kinase
Nathan, D. F., & Lindquist, S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.7.3917 · Cited by 423 · cited 1×
“cerevisiae have provided some of the best evidence for the physiological roles of Hsc82/Hsp90 (Picard et al., 1990a; Bohen and Yamamoto, 1993; Nathan and Lindquist, 1995), Ydj1/ Hsp40 (Caplan et al.”
BackgroundMeyer, B., Pray-Grant, M. G., Heuvel, J. P. V., & Perdew, G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.978 · Cited by 390
Chaperone Function of Hsp90-Associated Proteins
Bose, S., Weikl, T., Bügl, H., & Buchner, J. (1996) · Science · doi:10.1126/science.274.5293.1715 · Cited by 379
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–358 of 358
The Pivotal Role of CK2 in the Kinome‐Targeting Hsp90 Chaperone Machinery
Miyata, Y. (2013) · doi:10.1002/9781118482490.ch7 · Cited by 2
Regulation of gene transcription by the thyroid hormone receptors
Nygård, M. (2006) · Figshare · Cited by 2
D’Arrigo, P., Tufano, M., Rea, A., Romano, S., & Romano, M. F. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6438-9_101769-1 · Cited by 2
Genetic Markers for PTSD Risk and Resilience Among Survivors of the World Trade Center Attacks
Yehuda, R. (2012) · PsycEXTRA Dataset · doi:10.1037/e533652013-116 · Cited by 2
Yarushkina, N. I., & Filaretova, L. P. (2023) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-023-01460-2 · Cited by 1
Pilatti, F., Philippsen, M., Bertollo, A. G., WEBLER, C. P., Bordignon, A. K., & Ignácio, Z. M. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1801474 · Cited by 1
“Riggs et al. (2003) showed that it facilitates nuclear entry of the glucocorticoid receptor (GR), thereby allowing cortisol to function properly.”
Molecular Genomics of Mineralocorticoid Action
Fuller, P. J., & Young, M. J. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00043-7 · Cited by 1
Fazeli, A., & Jelodar, N. B. (2012) · Journal of Plant Pathology & Microbiology · doi:10.4172/scientificreports.152 · Cited by 1
Gehring, U. (2004) · Medizinische Klinik - Intensivmedizin und Notfallmedizin · doi:10.1007/s00063-004-1035-4 · Cited by 1
General Structural and Functional Features of Molecular Chaperones
Edkins, A. L., & Boshoff, A. (2013) · Springer eBooks · doi:10.1007/978-94-007-7438-4_2 · Cited by 1
Malcom, C. A., Guzeloglu‐Kayisli, O., Ün, B., New, E. P., Cetinkaya-Un, B., Guo, X., Mikhail, E., Imudia, A. N., Lockwood, C. J., & Kayisli, U. A. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf255
Plant Immunophilins: A Protein Family with Diverse Functions Beyond Protein Folding Activity
Shi, L., & Fu, A. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2211-6_14 · Cited by 1
Functional Protein Interactions in Steroid Receptor-Chaperone Complexes
Ratajczak, T., Rudi, K., Cluning, C., & Bryan, K. R. (2012) · InTech eBooks · doi:10.5772/38339 · Cited by 1
“…(Cheung-Flynn et al. , 2005) and PR (Tranguch et al. , 2005; Yang et al. , 2006), while similar influences of this immunophilin cochaperone on ER α (Riggs et al. , 2003) and MR (Gallo et al. , 2007) activity have not been observed, despite the assembly of FKBP52 with Hsp90 complexes containing…”
BackgroundMethodInfluentialSelf-citationAlaee, S. (2014) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2014.329 · Cited by 1
“These immunophilins have a similar structure, but FKBP52 increases the affinity of PR for its ligand while FKBP51 decreases this affinity, thereby reducing the response of target tissue to this hormone (17, 23-24).”
BackgroundCorticosteroid Receptors, Their Chaperones and Cochaperones: How Do They Modulate Adipogenesis?
Toneatto, J., Charó, N. L., Naselli, A., Muñoz-Bernart, M., Lombardi, A., & Piwien‐Pilipuk, G. (2014) · Nuclear Receptor Research · doi:10.11131/2014/101092 · Cited by 1
“FKBP51 and FKBP52 share 60% identity and 70% similarity; however, the former has been so far mainly reported to be a negative regulator of steroid hormone receptors while the latter is a positive one [103–105, 125, 127].”
BackgroundBioinspired Hybrid Fluorescent Ligands for the FK1 Domain of FKBP52
de la Sierra-Gallay, I. L., Belnou, M., Chambraud, B., Genet, M., TILBEURGH, H. V., Nicaise, M., Desmadril, M., Baulieu, É.-É., Jacquot, Y., & Byrne, C. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00825 · Cited by 1
Galigniana, M. D., Ciucci, S. M., & Mazaira, G. I. (2022) · Current Clinical Pharmacology · doi:10.2174/2772432817666220428135138 · Cited by 1
Torigoshi, T., Motokawa, S., Miyashita, T., Maeda, Y., Koga, T., Nakamura, M., Komori, A., Aiba, Y., Uemura, T., Yatsuhashi, H., et al. (2009) · PubMed · Cited by 1
Receptor-Independent Vitamin D Resistance in Subhuman and Human Primates
Adams, J. S., Chen, H., Lisse, T. S., Chun, R. F., & Hewison, M. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-303-9_38 · Cited by 1
Regulation of heat shock factor 1 (HSF1) DNA-binding and transcription
Mercier, P. A. (2003) · University Library - University of Saskatchewan (University of Saskatchewan) · Cited by 1
Chinkers, M. (2003) · Topics in current genetics · doi:10.1007/978-3-540-40035-6_6 · Cited by 1
“Overexpression of FKBP51 but not of PP5 blocks this stimulation by FKBP52 ( Riggs et al. 2003 ).”
BackgroundPearson, J. D. (2013) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3n697 · Cited by 1
Drugging the Hsp90 molecular chaperone machine for cancer treatment
Holmes, J. L., Sharp, S. Y., & Workman, P. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6401-2_15 · Cited by 1
“In a yeast model, Fkbp52 has been shown to dramatically potentiate glucocorticoid-dependent reporter gene activity through a mechanism that results in increased receptor hormone-binding affinity (Riggs et al. 2003).”
BackgroundHadley, K. (2010) · Open University of Cape Town (University of Cape Town) · Cited by 1
The Hsp 90 Family of Molecular Chaperones
Richter, K., Meinlschmidt, B., & Büchner, J. (2008) · Wiley eBooks · doi:10.1002/9783527610754.sf22
The Hsp90-Based Protein Trafficking System and Linkage to Protein Quality Control
Osawa, Y., Pratt, W. B., Morishima, Y., & Lieberman, A. P. (2012) · Heat shock proteins · doi:10.1007/978-94-007-4740-1_9
Tatro, E. T. (2008) · D-Scholarship@Pitt (University of Pittsburgh)
Molecular mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia
Tissing, W. J. E. (2006) · RePub (Erasmus University Rotterdam)
Wochnik, G. M. (2004) · Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.2498
Banerjee, A. T. (2007) · OhioLink ETD Center (Ohio Library and Information Network)
Hynne, M. S. (2008) · NORA - Norwegian Open Research Archives
ID4 and FKBP52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight
Joshi, J. (2016) · Atlanta University Center Robert W. Woodruff Library (Atlanta University Center Robert W. Woodruff Library)
FKBP52-Progesterone Receptor Signaling During Pregnancy
Tranguch, S. L. (2007)
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
Nuclear Mechanisms of Glucocorticoid Action
Hager, G. L., Stavreva, D. A., & Voss, T. C. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00040-1
Klengel, T., & Rein, T. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-29901-3_1
Chaperones and ADP-Ribosylating Bacterial Toxins
Barth, H., & Ernst, K. (2018) · Toxinology · doi:10.1007/978-94-007-6449-1_7
D’Arrigo, P., Tufano, M., Rea, A., Romano, S., & Romano, M. F. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_101769
Taubert, M. C., Kühn, A., Baischew, A., Käseberg, Y., Betschinske, J., & Hausch, F. (2025) · bioRxiv · doi:10.1101/2025.06.09.658717
“The co-chaperone FKBP51 is known for its inhibitory activity on the GR whereas FKBP52 promotes GR signaling [9], [10], [11], [12].”
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
Criado‐Marrero, M., Gebru, N. T., Blazier, D. M., Gould, L. A., Baker, J. D., Beaulieu‐Abdelahad, D., & Blair, L. J. (2021) · Figshare · doi:10.6084/m9.figshare.14391487
Rang social, système dopaminergique et réponse au stress
Battivelli, D. (2019) · theses.fr (ABES) · doi:10.70675/b11d29f4z1bf3z4003z81f9z8c69988b277b
Glucocorticoid receptor activity in triple negative breast cancer
Noureddine, L. M. (2022) · theses.fr (ABES) · doi:10.70675/13ab50cfz7edbz4a44z918aza657b9614a4d
Research Progress on Glucocorticoid-Sensitizing Drugs
张, 子. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1651955
Wang, X., Zeng, L., Qu, N., Bahat, B., & Zhu, H. (2026) · Pediatric Rheumatology · doi:10.1186/s12969-026-01231-6
“This underscores the need for more aggressive early intervention and individualized treatment strategies for pSLE [3–5].”
Bae, J., Han, G. H., Yun, H., Chung, J., Kim, J., & Cho, H. (2026) · Research Square · doi:10.21203/rs.3.rs-9525299/v1
SAV1 in Cooperation With FKBP52 Participates in Implantation
Shao, Y., Lu, Y., Jia, Z., Ren, J., Ge, Z., Liu, X., Zhao, H., Chen, Z., Yan, J., Wang, W., et al. (2026) · Advanced Science · doi:10.1002/advs.77761
“FKBP52 is a positive regulator of the glucocorticoid receptor (GR), PR, AR, but not ER [ 31, 47, 48 ].”
BindingDB (2013) · UC San Diego · doi:10.7270/q2qj7jcv
BindingDB Entry 50010920: Bioinspired Hybrid Fluorescent Ligands for the FK1 Domain of FKBP52.
BindingDB (2021) · UC San Diego · doi:10.7270/q2qc0735
BindingDB Entry 50008490: A Novel Decalin-Based Bicyclic Scaffold for FKBP51-Selective Ligands.
BindingDB (2021) · UC San Diego · doi:10.7270/q2q52t10
Metadata
- Authors
- Riggs, D. L., Roberts, P. J., Chirillo, S. C., Cheung‐Flynn, J., Prapapanich, V., Ratajczak, T., Gaber, R., Picard, D., & Smith, D. F.
- Affiliations
- Mayo Clinic (US)
- The University of Western Australia (AU)
- Northwestern University (US)
- University of Geneva (CH)
- Corresponding author
- Smith, David F.
- Venue
- The EMBO Journal
- Published
- 2003-03-03
- Volume
- 22
- Issue
- 5
- Pages
- 1158-1167
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC150341
- OpenAlex
- W2075431153
- Semantic Scholar
- 1ac04c1350d5c46f954ac9ade4bc83458748b0ac
- Cited by
- 353
- References
- 58
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 6 · 2023: 19 · 2022: 13 · 2021: 16 · 2020: 13 · 2019: 16 · 2018: 9 · 2017: 14 · 2016: 15 · 2015: 21 · 2014: 16 · 2013: 18 · 2012: 16
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation (0079249)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK44923, R01DK044923, R01DK048218)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- FKBP52, HSP90, immunophilins, glucocorticoid receptor, glucocorticoid signaling, peptidylprolyl isomerase, FKBP51, hormone binding affinity, Saccharomyces cerevisiae, protein phosphatase 5
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Gene Expression Regulation, Glucocorticoids, Humans, Models, Molecular, Protein Binding, Protein Conformation, Receptors, Glucocorticoid, Saccharomyces cerevisiae, Signal Transduction, Transcriptional Activation, Genes, Reporter, Molecular Chaperones, HSP90 Heat-Shock Proteins, Peptidylprolyl Isomerase, Tacrolimus Binding Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
