FKBP52
FKBP52 is an Hsp90-binding immunophilin and peptidyl-prolyl isomerase that acts as a positive regulator of steroid hormone receptor signaling, especially androgen receptor, glucocorticoid receptor, and progesterone receptor pathways[1][2]. Mechanistically, FKBP52 associates with receptor-Hsp90 complexes, supports hormone binding and receptor localization, and directly binds the folded, ligand-bound glucocorticoid receptor in the GR:Hsp90:FKBP52 complex[2][3]. In prostate cancer models, FKBP52 supports androgen receptor activity, β-catenin interaction with AR, AR dimer formation, chromatin binding, and phosphorylation[4][5][6]. Compared with the related isoform FKBP51, FKBP52 shows functional divergence despite structural similarity, and cryo-EM evidence shows FKBP51 competes with FKBP52 for GR:Hsp90 binding and antagonizes FKBP52-dependent GR activity[2][3]. For experimental applications, MJC13 inhibits FKBP52-regulated AR signaling by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex and by blocking β-catenin interaction with the AR ligand-binding domain[4][5].
Verweise:
- [1]. Riggs DL, et al. The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. EMBO J. 2003 Mar 3;22(5):1158-67. [Content Brief]
- [2]. Storer CL, et al. FKBP51 and FKBP52 in signaling and disease. Trends Endocrinol Metab. 2011 Dec;22(12):481-90. [Content Brief]
- [3]. Noddings CM, et al. Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor. Nat Struct Mol Biol. 2023 Dec;30(12):1867-1877. [Content Brief]
- [4]. De Leon JT, et al. Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11878-83. [Content Brief]
- [5]. Storer Samaniego C, et al. The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling. PLoS One. 2015 Jul 24;10(7):e0134015. [Content Brief]
- [6]. Maeda K, et al. FKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells. Mol Oncol. 2022 Feb;16(4):940-956. [Content Brief]
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FKBP52 Verwandte Produkte (1)
Verwandte Produkte (1)
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ILS-920
0 ImagesILS-920 is a nonimmunosuppressive Rapamycin analog with reduced immunosuppressive activity and potent neuroprotective activity. ILS-920 binds selectively to the immunophilin FKBP52 and to the β1-subunit of L-type voltage-gated calcium channels (VGCC). ILS-920 shows 200-fold selectivity for FKBP52 versus FKBP12.
