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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 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]
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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]
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“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
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Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor
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“FKBP51 is functionally antagonistic to FKBP52-dependent potentiation of GR in vivo; thus, the relative ratios of FKBP51 and FKBP52 dictate GR activity levels 23,28,55 .”
BackgroundMethodResultInfluentialBaker, J. D., McMillan, I. O., Ospina, S. R., Gulick, D., & Blair, L. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010079 · Cited by 74
“FKBP4, the gene that encodes the highly similar FKBP51 homolog, FKBP52, may have an opposing effect on GR activity; however, conflicting evidence suggests FKBP52 may not alter GR nuclear transactivation [32,35,36,65,66].”
BackgroundFocus on FKBP51: A molecular link between stress and metabolic disorders
Häusl, A. S., Balsevich, G., Gassen, N. C., & Schmidt, M. V. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.003 · Cited by 73
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“(24) observed that overexpression of the immunophilins FKBP51 and FKBP52, in yeast cells caused an increase in GR protein levels.”
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“Thus, the yeast-based steroid hormone receptor-mediated reporter assay using a chemiluminescent substrate has been used extensively for the analysis of receptor regulatory proteins (Balsiger and Cox, 2009; Cox et al., 2007; Riggs et al., 2007; Riggs et al., 2003).”
BackgroundMethodFKBP family proteins as promising new biomarkers for cancer
Solassol, J., Mangé, A., & Maudelondé, T. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.03.012 · Cited by 67
Deficiency of Immunophilin FKBP52 Promotes Endometriosis
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“Furthermore, the inhibitory activity of FKBP51 was quite specific because the coexpression of another TPR-containing protein, protein phosphatase 5, did not affect potentiation by FKBP52 (23).”
BackgroundInfluentialSelf-citationDose- and time-dependent glucocorticoid receptor signaling in podocytes
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FK506 binding protein 51 integrates pathways of adaptation
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“This review portraits FK506 binding protein (FKBP) 51 as ‘‘reactivity protein’’ and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation.”
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FKBP4 is regulated by HOXA10 during decidualization and in endometriosis
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“This role, as a co-chaperone of HSP90, enables FKBP4 to govern normal PR function in the mouse uterus (Reynolds et al. 1999, Riggs et al. 2003, Davies et al. 2005, Davies & Sanchez 2005).”
BackgroundEvaluation of synthetic FK506 analogues as ligands for the FK506-binding proteins 51 and 52
Gopalakrishnan, R., Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., & Hausch, F. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201746x · Cited by 64
FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications
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“To assess FKBP52 mutant function in cells, we employed an established yeast model for FKBP52 activity (4) in which steroid receptors drive expression of a -galactosidase reporter gene in a hormone-dependent and FKBP52-enhanced manner.”
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“4B), which is in line with previous studies in other cell types suggesting that FKBP52 associates with GR to promote its nuclear translocation (Riggs et al., 2003; Warrier et al., 2010).”
BackgroundResultInfluentialFKBP51 Reciprocally Regulates GRα and PPARγ Activation via the Akt-p38 Pathway
Stechschulte, L. A., Hinds, T. D., Ghanem, S. S., Shou, W., Najjar, S. M., & Sánchez, E. R. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1023 · Cited by 59
The Heat Shock Protein 70 Cochaperone Hip Enhances Functional Maturation of Glucocorticoid Receptor
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“(10, 64) and because estradiol causes down-regulation of”
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“It has been shown that both bind competitively to the same site on the Hsp90 complex (Nair et al., 1997; Young et al., 1998) and that shuffling between the two effects the subcellular localization and transport of steroid receptors (Davies et al., 2002, 2005; Riggs et al., 2003).”
Toneatto, J., Guber, S., Charó, N. L., Susperreguy, S., Schwartz, J., Galigniana, M. D., & Piwien‐Pilipuk, G. (2013) · Journal of Cell Science · doi:10.1242/jcs.125799 · Cited by 55
“…share 60% identity and 70% similarity; however, the former has, so far, been mainly reported to be a negative regulator of steroid hormone receptors while the latter is a positive regulator (Davies et al., 2002; Gallo et al., 2007; Riggs et al., 2003; Storer et al., 2011; Wochnik et al., 2005).”
BackgroundProgesterone receptor requires a co-chaperone for signalling in uterine biology and implantation
Tranguch, S. L., Smith, D. F., & Dey, S. K. (2006) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)60655-4 · Cited by 53
“For example, FKBP52 potentiates the responses of PR, androgen receptor, and glucocorticoid receptor to hormone (Riggs et al., 2003; Cheung-Flynn et al., 2005; Tranguch et al., 2005), whereas FKBP51 can attenuate hormonal responsiveness (Reynolds et al.”
BackgroundInfluentialSelf-citationHsp90 co-chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild-type mice
Criado‐Marrero, M., Gebru, N. T., Blazier, D. M., Gould, L. A., Baker, J. D., Beaulieu‐Abdelahad, D., & Blair, L. J. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01159-w · Cited by 53
“FKBP52 is an Hsp90 co-chaperone highly expressed in neurons and a regulator of steroid hormone complexes [76, 103].”
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Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins 51 and 52
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Functional Comparison of Human and Drosophila Hop Reveals Novel Role in Steroid Receptor Maturation
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Self-citationInterAKTions with FKBPs - Mutational and Pharmacological Exploration
Fabian, A., März, A., Neimanis, S., Biondi, R. M., Kozany, C., & Hausch, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057508 · Cited by 51
“Cox [49].”
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“Hsc70 often functions together with the 90-kDa heat shock protein (Hsp90) and may be considered a single, multi-chaperone complex mediating the folding of a smaller subset of client proteins that includes steroid hormone receptors [13,14], regulatory kinases, and transcription factors [15,16].”
BackgroundAdvances towards Understanding the Mechanism of Action of the Hsp90 Complex
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“FKBP51 appears to block potentiation [45].”
Oh, E. S., Yeung, C., Babaei-Rad, R., & Zhao, R. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-643 · Cited by 45
“All known eukaryotic cytosolic HSP90s contain a MEEVD motif at the C-terminus that is essential for the binding of proteins with tetratricopeptide repeat (TPR) domains [23,24], such as cochaperones HOP/Sti1, Cpn6, and Cpn7 which modulate cytosolic HSP90 function [25,26].”
BackgroundEvaluation of the 4q32-34 Locus in European Familial Pancreatic Cancer
Earl, J., Yan, L., Vitone, L. J., Risk, J. M., Kemp, S. J., McFaul, C., Neoptolemos, J. P., Greenhalf, W., for the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer, Kress, R., et al. (2006) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-06-0376 · Cited by 47
“PPID is also associated with the cancer-related stress protein Hsp 90 and involved in targeting Hsp 90 to inactive glucocorticoid receptor (36) and dynein (37).”
BackgroundBracher, A., Kozany, C., Hähle, A., Wild, P., Zacharias, M., & Hausch, F. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.07.041 · Cited by 45
Proline Isomerization: From the Chemistry and Biology to Therapeutic Opportunities
Gurung, D., Danielson, J. A., Tasnim, A., Zhang, J., Zou, Y., & Liu, J. (2023) · Biology · doi:10.3390/biology12071008 · Cited by 50
“The role of PPIases in cancer has been reviewed by several other authors and it is recommended to refer to them for more in-depth information [81,178,185,186].”
BackgroundSmall molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent
Harikishore, A., Niang, M., Rajan, S. S., Preiser, P. R., & Yoon, H. S. (2013) · Scientific Reports · doi:10.1038/srep02501 · Cited by 46
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Regulatory Mechanisms of Heat Stress Response and Thermomorphogenesis in Plants
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“1 can also form a complex with ROF1/AFKBP62 (rotamase FKBP 1) to respond to heat stress [55,56].”
BackgroundPeptidyl-Prolyl cis/trans Isomerase-Independent Functional NifH Mutant of Azotobacter vinelandii
Gavini, N., Tungtur, S. K., & Pulakat, L. (2006) · Journal of Bacteriology · doi:10.1128/jb.00379-06 · Cited by 43
“PPIases are regulators of a variety of biological functions, such as cell cycle progression (Pin1 and ESS1) (4, 10, 16), the inhibition of apoptosis (cyclophilins A) (17), carcinogenesis (Pin1) (2), association with hormone receptors (FKBP52/ CyP40) ( 24 ), and bacterial infection (MIP) (14, 21), to name a few.”
BackgroundCortisol resistance in the New World revisited
Fuller, P. J., Smith, B. J., & Rogerson, F. M. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.07.001 · Cited by 42
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“Moreover, p23 and FKBP4 are required for the maturation of steroid hormone receptors (Dittmar et al., 1997; Morishima et al., 2003; Riggs et al., 2003; Pratt et al., 2004; Wochnik et al., 2005).”
BackgroundRepouskou, A., Papadopoulou, A.-K., Panagiotidou, E., Trichas, P., Lindh, C. H., Bergman, Å., Gennings, C., Bornehag, C., Rüegg, J., Kitraki, E., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-66379-x · Cited by 43
PTSD: Past, present and future implications for China
Zhou, Y., Shang, Z., Zhang, F., Wu, L., Sun, L., Jia, Y., Yu, H., & Liu, W. (2021) · Chinese Journal of Traumatology · doi:10.1016/j.cjtee.2021.04.011 · Cited by 43
Tissing, W. J. E., Meijerink, J. P. P., den Boer, M. L., Brinkhof, B., & Pieters, R. (2005) · Leukemia · doi:10.1038/sj.leu.2403681 · Cited by 40
Edlich, F., & Fischer, G. S. (2005) · Handbook of experimental pharmacology · doi:10.1007/3-540-29717-0_15 · Cited by 40
“Cross-talk between Hsp90 and FKBP52 has been observed for the interaction of FKBP52 with the single-stranded D-sequence binding protein of the adenoassociated virus type 2 that is important for the prevention of viral replication (Zhong et al. 2004).”
BackgroundInfluentialShi, D., Bai, Q., Zhou, S., Liu, X., Liu, H., & Yao, X. (2017) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25401 · Cited by 38
Dahiya, V., Rutz, D. A., Moessmer, P., Mühlhofer, M., Lawatscheck, J., Rief, M., & Büchner, J. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.01.016 · Cited by 39
Oxelmark, E., Knoblauch, R. E., Arnal, S. M., Su, L. F., Schapira, M., & Garabedian, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305960200 · Cited by 38
Wolf, I. M., Periyasamy, S., Hinds, T., Yong, W., Shou, W., & Sanchez, E. R. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.11.006 · Cited by 38
“Both the Smith and Rein laboratories have shown that potentiation of GR activity requires the PPIase domain [23,34].”
BackgroundResultHsp90 can accommodate the simultaneous binding of the FKBP52 and HOP proteins
Hildenbrand, Z. L., Molugu, S. K., Herrera, N., Ramirez, C., Xiao, C., & Bernal, R. A. (2011) · Oncotarget · doi:10.18632/oncotarget.225 · Cited by 38
“These findings reveal that FKBP52-mediated potentiation of receptor activity is significantly abrogated in glucocorticoid (GR), androgen (AR) and progesterone (PR) receptor models [34, 42-45].”
BackgroundInfluentialMok, D., Allan, R. K., Carrello, A., Wangoo, K., Walkinshaw, M. D., & Ratajczak, T. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.04.039 · Cited by 37
“In addition to PPIase function and Hsp90 binding, chaperone activity has been reported for CyP40 [11,12], FKBP51 [12] and FKBP52 [11,13], as well as for p23, a partner cochaperone present in mature steroid receptor heterocomplexes [6,14,15].”
BackgroundInfluentialSelf-citationXAP2 inhibits glucocorticoid receptor activity in mammalian cells
Laenger, A., Lang‐Rollin, I., Kozany, C., Zschocke, J., Zimmermann, N., Rüegg, J., Holsboer, F., Hausch, F., & Rein, T. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.03.072 · Cited by 38
“The highly homologues immunophilins FKBP51 and FKBP52 display differential effects on GR folding and nuclear translocation [7,11].”
BackgroundInfluentialHori, H., Sasayama, D., Teraishi, T., Yamamoto, N., Nakamura, S., Ota, M., Hattori, K., Kim, Y., Higuchi, T., & Kunugi, H. (2016) · Scientific Reports · doi:10.1038/srep18776 · Cited by 38
The immunophilin FKBP52 inhibits the activity of the epithelial Ca2+channel TRPV5
Gkika, D., Topala, C. N., Hoenderop, J. G. J., & Bindels, R. J. M. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00298.2005 · Cited by 38
“The enzymatic activity of FKBP52 was abolished by double mutation of two highly conserved amino acid residues (FD67DV mutant) as described previously (22).”
BackgroundFKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells
Maeda, K., Habara, M., Kawaguchi, M., Matsumoto, H., Hanaki, S., Masaki, T., Sato, Y., Matsuyama, H., Kunieda, K., Nakagawa, H., et al. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13030 · Cited by 32
Sex differences in hypothalamic–pituitary–adrenal axis regulation after chronic unpredictable stress
Palumbo, M. C., Dominguez, S., & Dong, H. (2020) · Brain and Behavior · doi:10.1002/brb3.1586 · Cited by 39
“Several reports have characterized FKBP51 as a strong inhibitor of GR function (Fries, Gassen, Schmidt, & Rein, 2015; Riggs et al., 2003), reducing transcriptional activity, (Wochnik et al., 2005) and delaying nuclear translocation of the receptor.”
BackgroundSelf-Assembly by Mutual Association: Basic Thermodynamic Properties
Dudowicz, J., Douglas, J. F., & Freed, K. F. (2008) · The Journal of Physical Chemistry B · doi:10.1021/jp806859w · Cited by 36
The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
Romano, S., Sorrentino, A., Pace, A. L. D., Nappo, G., Mercogliano, C. J., & Romano, M. F. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711798194333 · Cited by 36
“Despite their similarities, the cochaperones FKBP51 and FKBP52 have distinctive properties for binding and assembling with Hsp90 in steroid receptor complexes [16,18].”
BackgroundInfluentialGeneral Structural and Functional Features of Molecular Chaperones
Edkins, A. L., & Boshoff, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-78397-6_2 · Cited by 34
Hsp90 Co-chaperones Form Plastic Genetic Networks Adapted to Client Maturation
Biebl, M. M., Riedl, M., & Büchner, J. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108063 · Cited by 36
Herbelet, S., Rodenbach, A., Paepe, B. D., & Bleecker, J. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134596 · Cited by 38
Functions of the Hsp90-Binding FKBP Immunophilins
Guy, N. C., Garcia, Y. A., Sivils, J. C., Galigniana, M. D., & Cox, M. B. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_2 · Cited by 36
“In concordance with hormone binding affinity changes, domain-swapping experiments between GR and ER, which is not potentiated by FKBP52, demonstrated that FKBP52 potentiation is localized to the ligand binding domain of GR (Riggs et al. 2003).”
BackgroundInfluentialNguyễn, M. T., Knieß, R. A., Daturpalli, S., Breton, L. L., Ke, X., Chen, X., & Mayer, M. P. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.01.011 · Cited by 32
Thr90 phosphorylation of Hsp90α by protein kinase A regulates its chaperone machinery
Wang, X., Lu, X., Song, X., Zhuo, W., Jia, L., Jiang, Y., & Luo, Y. (2011) · Biochemical Journal · doi:10.1042/bj20110855 · Cited by 34
Steroid Receptor-Associated Immunophilins: A Gateway to Steroid Signalling.
Ratajczak, T., Cluning, C., & Ward, B. K. (2015) · Europe PMC (PubMed Central) · Cited by 32
Self-citationOchi, S., Roy, B., Prall, K., Shelton, R. C., & Dwivedi, Y. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02263-0 · Cited by 34
Analysis of Hsp90 Cochaperone Interactions Reveals a Novel Mechanism for TPR Protein Recognition
Chadli, A., Bruinsma, E. S., Stensgard, B. A., & Toft, D. O. (2008) · Biochemistry · doi:10.1021/bi7023332 · Cited by 33
van Oosten‐Hawle, P. (2023) · Biomolecules · doi:10.3390/biom13020251 · Cited by 34
The impact of genetic factors on response to glucocorticoids therapy in IBD
Gabryel, M., Skrzypczak-Zielińska, M., Kucharski, M., Słomski, R., & Dobrowolska, A. (2016) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2015.1132336 · Cited by 30
Ernst, K., Schnell, L., & Barth, H. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_14 · Cited by 31
The Role of p23, Hop, Immunophilins, and Other Co-chaperones in Regulating Hsp90 Function
Cox, M. B., & Johnson, J. L. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-295-3_4 · Cited by 32
Steroid regulation of menstrual bleeding and endometrial repair
Maybin, J. A., & Critchley, H. (2012) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-012-9228-2 · Cited by 32
“FKBP52 has a positive regulatory impact on the GR, PR and AR, but not ER or the mineralocorticoid receptor (MR) [109–111].”
BackgroundHirakawa, H., Akiyoshi, J., Muronaga, M., Tanaka, Y., Ishitobi, Y., Inoue, A., Oshita, H., Aizawa, S., Masuda, K., Higuma, H., et al. (2016) · International Journal of Psychiatry in Clinical Practice · doi:10.3109/13651501.2016.1144772 · Cited by 30
“protein 52 (FKBP52 or FKBP4), a positive regulator of GR signaling (Riggs et al. 2003).”
BackgroundBirge, R. B., Wadsworth, S., Akakura, R., Abeysinghe, H. C. S., Kanojia, R., Macielag, M. J., Desbarats, J., Escalante, M., Singh, K. K., Sundarababu, S., et al. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.10.013 · Cited by 30
The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51
Antunica-Noguerol, M., Budziñski, M. L., Druker, J., Gassen, N. C., Sokn, C., Senin, S. A., Aprile-Garcia, F., Holsboer, F., Rein, T., Liberman, A. C., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.44 · Cited by 29
“Upon hormone stimulation, there is a switch from FKBP51 to the closely related TPR protein, FKBP52, which positively regulates GR activity.(5,7,8) Therefore, we analyzed whether impairment of SUMO conjugation to FKBP51 alters the cochaperone composition of this complex.”
BackgroundDeficiency of co-chaperone immunophilin FKBP52 compromises sperm fertilizing capacity
Hong, J., Kim, S. T., Tranguch, S., Smith, D. F., & Dey, S. K. (2007) · Reproduction · doi:10.1530/rep-06-0180 · Cited by 28
“…several studies suggest that FKBP52 plays a role in nuclear transport of receptor complexes, DOI: 10.1530/REP-06-0180 Online version via www.reproduction-online.org it is not clear whether this role is physiologically critical (Riggs et al. 2003, Cheung-Flynn et al. 2005, Davies & Sanchez 2005).”
BackgroundInfluentialSelf-citationFox, J. E., Burow, M. E., McLachlan, J. A., & Miller, C. A. (2008) · Nature Protocols · doi:10.1038/nprot.2008.33 · Cited by 28
Hsp70 Cochaperones HspBP1 and BAG-1M Differentially Regulate Steroid Hormone Receptor Function
Knapp, R., Wong, M. J. H., Kollmannsberger, L. K., Gassen, N. C., Kretzschmar, A., Zschocke, J., Hafner, K., Young, J. C., & Rein, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085415 · Cited by 28
“The different cellular protein endowment could produce a seeming divergence in function of some proteins between yeast and mammals, as suggested for the effects of the Hsp90 cochaperones FKBP51 and FKBP52 on GR activity [29,42].”
BackgroundKamah, A., Cantrelle, F., Huvent, I., Giustiniani, J., Guillemeau, K., Byrne, C., Jacquot, Y., Landrieu, I., Baulieu, E. E., Smet‐Nocca, C., et al. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.015 · Cited by 28
Adamantyl derivative as a potent inhibitor of Plasmodium FK506 binding protein 35.
Harikishore, A., Leow, M., Niang, M., Rajan, S., Pasunooti, K., Preiser, P., Liu, X.-W., & Yoon, H. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml400306r · Cited by 23
Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism
Häusl, A. S., Bajaj, T., Brix, L. M., Pöhlmann, M. L., Hafner, K., Angelis, M. D., Nagler, J., Dethloff, F., Balsevich, G., Schramm, K., et al. (2022) · Science Advances · doi:10.1126/sciadv.abi4797 · Cited by 27
The helix 1–3 loop in the glucocorticoid receptor LBD is a regulatory element for FKBP cochaperones
Cluning, C., Ward, B. K., Rea, S. L., Arulpragasam, A., Fuller, P. J., & Ratajczak, T. (2013) · Molecular Endocrinology · doi:10.1210/me.2012-1023 · Cited by 26
Self-citationPark, J., Kim, M., Na, G., Jeon, I., Kwon, Y.-K., Kim, J.-H., Youn, H., & Koo, Y. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.08.002 · Cited by 26
FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer
Habara, M., Sato, Y., Goshima, T., Sakurai, M., Imai, H., Shimizu, H., Katayama, Y., Hanaki, S., Masaki, T., Morimoto, M., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2110256119 · Cited by 27
Peptidylprolylisomerases, Protein Folders, or Scaffolders? The Example of FKBP51 and FKBP52
Rein, T. (2020) · BioEssays · doi:10.1002/bies.201900250 · Cited by 25
Structure-Based Discovery of a New Selectivity-Enabling Motif for the FK506-Binding Protein 51
Knaup, F. H., Meyners, C., Sugiarto, W. O., Wedel, S., Springer, M., Walz, C., Geiger, T. M., Schmidt, M. V., Sisignano, M., & Hausch, F. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00249 · Cited by 25
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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