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J. Biol. Chem. 277 (23): 20702-20710

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Liganded Androgen Receptor Interaction with beta -Catenin
NUCLEAR CO-LOCALIZATION AND MODULATION OF TRANSCRIPTIONAL ACTIVITY IN NEURONAL CELLS*

John E. PawlowskiDagger , Jessica R. ErtelDagger , Melissa P. AllenDagger , Mei XuDagger , Cheryl ButlerDagger , Elizabeth M. Wilson§, and Margaret E. WiermanDagger

From the Dagger  Research Service, Veterans Affairs Medical Center and Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80220 and § Laboratory of Reproductive Biology, University of North Carolina, Chapel Hill, North Carolina 27599

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-(Delta 371-485)) as a bait, beta -catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-beta -catenin demonstrated that FLAG-beta -catenin was predominantly cytoplasmic in the absence of androgen. In the presence of 5alpha -dihydrotestosterone, FLAG-beta -catenin completely co-localized to the nucleus with AR. This effect was specific to AR because liganded progesterone, glucocorticoid, or estrogen alpha  receptors did not translocate FLAG-beta -catenin to the nucleus. Agonist-bound AR was required because the AR antagonists casodex and hydroxyflutamide failed to translocate beta -catenin. Time course experiments demonstrated that co-translocation occurred with similar kinetics. Nuclear co-localization was independent of the glycogen synthase kinase-3beta , 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 beta -catenin/T cell factor-responsive reporter gene activity. Conversely, co-expression of beta -catenin/T cell factor repressed AR stimulation of AR-responsive reporter gene activity. Our data suggest that liganded AR shuttles beta -catenin to the nucleus and that nuclear interaction of AR with beta -catenin may modulate transcriptional activity in androgen target tissues.

* This work was supported by a Veterans Affairs Merit award (to M. E. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Endocrinology (111H), Veterans Affairs Medical Center, 1055 Clermont St., Denver, CO 80220. Tel.: 303-399-8020 (Ext. 3150); Fax: 303-393-5271; E-mail: margaret.wierman@uchsc.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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