PlumX Metrics
Embed PlumX Metrics

Essential Role for Co-chaperone Fkbp52 but Not Fkbp51 in Androgen Receptor-mediated Signaling and Physiology *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 282, Issue: 7, Page: 5026-5036
2007
  • 130
    Citations
  • 0
    Usage
  • 62
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

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.

Bibliographic Details

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

American Society for Biochemistry & Molecular Biology (ASBMB)

Biochemistry, Genetics and Molecular Biology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know