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.
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“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]
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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]
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“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]
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“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]
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“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]
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“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]
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“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]
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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
Cited by
Sorted by citations
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818
“These functions seem to be dispensable for client activation in at least one case (that of FKBP52 -dependent potentiation of glucocorticoid receptor functio”
BackgroundPathways of chaperone-mediated protein folding in the cytosol
Young, J. C., Agashe, V. R., Siegers, K., & Hartl, F. U. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1492 · Cited by 1,121
“pl?Q02790">FKB4 ), which is an immunophilin with peptidyl-prolyl cis – trans isomerase activity and a TPR-clamp domain, replaces HOP on HSP90 at this stage and enhances receptor foldin”
BackgroundZhao, R., Davey, M., Hsu, Y.-C., Kaplanek, P., Tong, A., Parsons, A. B., Krogan, N., Cagney, G., Mai, D., Greenblatt, J., et al. (2005) · Cell · doi:10.1016/j.cell.2004.12.024 · Cited by 819
“For the GR maturation assay, the trains were transformed with a plasmid expressing GR nder the control of a constitutive promoter along with reporter plasmid in which the expression of lacZ reorter gene was placed under the control of a GResponse element (GRE) (Riggs et al., 2003).”
MethodThe Aryl Hydrocarbon Receptor Complex and the Control of Gene Expression
Beischlag, T. V., Morales, J. L., Hollingshead, B. D., & Perdew, G. H. (2008) · Critical Reviews™ in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v18.i3.20 · Cited by 727
“Interestingly, although they are closely related proteins, FKBP51 acts as a repressor of the GR, whereas the presence of FKBP52 in the GR complex enhances receptor transcriptional activity.(165,166) Also, it has been suggested that hormone binding to the GR stimulates the switching of the binding status of receptor fr…”
BackgroundWochnik, G. M., Rüegg, J., Abel, G. A., Schmidt, U., Holsboer, F., & Rein, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m407498200 · Cited by 638
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
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