Essential role for co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology

Weidong Yong, Zuocheng Yang, Sumudra Periyasamy, Hanying Chen, Selcul Yucel, Wei Li, Leanne Y. Lin, Irene M. Wolf, Martin J. Cohn, Laurence S. Baskin, Edwin R. Sánchez, Weinian Shou

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108 Citations (Scopus)

Abstract

Fkbp52 and Fkbp51 are tetratricopeptide repeat proteins found in steroid receptor complexes, and Fkbp51 is an androgen receptor (AR) target gene. Although in vitro studies suggest that Fkbp52 and Fkbp51 regulate hormone binding and/or subcellular trafficking of receptors, the roles of Fkbp52 and Fkbp51 in vivo have not been extensively investigated. Here, we evaluate their physiological roles in Fkbp52-deficient and Fkbp51-deficient mice. Fkbp52-deficient males developed defects in select reproductive organs (e.g. penile hypospadias and prostate dysgenesis but normal testis), pointing to a role for Fkbp52 in AR-mediated signaling and function. Surprisingly, ablation of Fkbp52 did not affect AR hormone binding or nuclear translocation in vivo and in vitro. Molecular studies in mouse embryonic fibroblast cells uncovered that Fkbp52 is critical to AR transcriptional activity. Interestingly, Fkbp51 expression was down-regulated in Fkbp52-deficient males but only in affected tissues, providing further evidence of tissue-specific loss of AR activity and suggesting that Fkbp51 is an AR target gene essential to penile and prostate development. However, Fkbp51-deficient mice were normal, showing no defects in AR-mediated reproductive function. Our work demonstrates that Fkbp52 but not Fkbp51 is essential to AR-mediated signaling and provides evidence for an unprecedented Fkbp52 function, direct control of steroid receptor transcriptional activity.

Original languageEnglish
Pages (from-to)5026-5036
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number7
DOIs
StatePublished - Feb 16 2007

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Physiology
Androgen Receptors
Steroid Receptors
Prostate
Genes
Hormones
Tissue
Hypospadias
Defects
Essential Genes
Fibroblasts
Ablation
Testis
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Essential role for co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology. / Yong, Weidong; Yang, Zuocheng; Periyasamy, Sumudra; Chen, Hanying; Yucel, Selcul; Li, Wei; Lin, Leanne Y.; Wolf, Irene M.; Cohn, Martin J.; Baskin, Laurence S.; Sánchez, Edwin R.; Shou, Weinian.

In: Journal of Biological Chemistry, Vol. 282, No. 7, 16.02.2007, p. 5026-5036.

Research output: Contribution to journalArticle

Yong, W, Yang, Z, Periyasamy, S, Chen, H, Yucel, S, Li, W, Lin, LY, Wolf, IM, Cohn, MJ, Baskin, LS, Sánchez, ER & Shou, W 2007, 'Essential role for co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology', Journal of Biological Chemistry, vol. 282, no. 7, pp. 5026-5036. https://doi.org/10.1074/jbc.M609360200
Yong, Weidong ; Yang, Zuocheng ; Periyasamy, Sumudra ; Chen, Hanying ; Yucel, Selcul ; Li, Wei ; Lin, Leanne Y. ; Wolf, Irene M. ; Cohn, Martin J. ; Baskin, Laurence S. ; Sánchez, Edwin R. ; Shou, Weinian. / Essential role for co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 7. pp. 5026-5036.
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AU - Chen, Hanying

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