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Liganded Androgen Receptor Interaction with β-Catenin
A yeast two-hybrid assay was employed to identify androgen receptor (AR) protein partners in gonadotropin-releasing hormone neuronal cells. By using an AR deletion construct (AR-(Î371â485)) as a bait, β-catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neu...
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Published in: | The Journal of biological chemistry 2002-06, Vol.277 (23), p.20702 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | A yeast two-hybrid assay was employed to identify androgen receptor (AR) protein partners in gonadotropin-releasing hormone
neuronal cells. By using an AR deletion construct (AR-(Î371â485)) as a bait, β-catenin was identified as an AR-interacting
protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-β-catenin
demonstrated that FLAG-β-catenin was predominantly cytoplasmic in the absence of androgen. In the presence of 5α-dihydrotestosterone,
FLAG-β-catenin completely co-localized to the nucleus with AR. This effect was specific to AR because liganded progesterone,
glucocorticoid, or estrogen α receptors did not translocate FLAG-β-catenin to the nucleus. Agonist-bound AR was required because
the AR antagonists casodex and hydroxyflutamide failed to translocate β-catenin. Time course experiments demonstrated that
co-translocation occurred with similar kinetics. Nuclear co-localization was independent of the glycogen synthase kinase-3β,
p42/44 ERK mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways because inhibitors of these pathways
had no effect. Transcription assays demonstrated that liganded AR repressed β-catenin/T cell factor-responsive reporter gene
activity. Conversely, co-expression of β-catenin/T cell factor repressed AR stimulation of AR-responsive reporter gene activity.
Our data suggest that liganded AR shuttles β-catenin to the nucleus and that nuclear interaction of AR with β-catenin may
modulate transcriptional activity in androgen target tissues. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M200545200 |