Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity

• Published in: Endocrine Vol. 26; no. 1; pp. 1 - 9
• Main Authors: Ting, Huei-Ju, Bao, Bo-Ying, Hsu, Cheng-Lung, Lee, Yi-Fen
• Format: Journal Article
• Language: English
• Published: United States 01.02.2005
• Subjects: Amino Acid Motifs; Animals; Calcitriol - antagonists & inhibitors; Calcitriol - metabolism; Calcitriol - pharmacology; Cell Line, Tumor; Cercopithecus aethiops; COS Cells; DNA-Binding Proteins - pharmacology; Gelsolin - pharmacology; Glutathione Transferase - metabolism; Histone Acetyltransferases; Hormone Antagonists - pharmacology; Humans; Intracellular Signaling Peptides and Proteins - pharmacology; Male; Membrane Proteins - pharmacology; Microfilament Proteins - pharmacology; Nuclear Receptor Co-Repressor 2; Nuclear Receptor Coactivator 1; Nuclear Receptor Coactivators; Oncogene Proteins - pharmacology; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Receptors, Androgen - metabolism; Receptors, Calcitriol - metabolism; Repressor Proteins - pharmacology; Transcription Factors - pharmacology; Transcriptional Activation - drug effects; Transfection; Two-Hybrid System Techniques
• ISSN: 1355-008X
• DOI: 10.1385/endo:26:1:001

Overexpression of androgen receptors (AR) in PC-3 cell, and treatment of 5alpha-dihydrotestosterone in LNCaP cells lead to the suppression of VDR transactivation. Competition for shared coregulators between AR and VDR is one possible mechanism to explain the suppressive effect of androgen-AR signals on VDR activity. Among the AR coregulators we tested, ARA54, ARA70, supervillin, and gelsolin were found to enhance VDR transactivation. Further characterization of the interaction between ARA54 or ARA70 and VDR demonstrated a direct interaction between VDR and ARA70, but no association between ARA54 and VDR. The LXXLL motif of ARA70 is essential for interaction with VDR and partially responsible for its function as a coactivator of VDR. The suppression of VDR transactivation by AR signal was restored by overexpression of ARA70, but not ARA54. Together, ARA70 and ARA54 modulate VDR transactivation, and the competition for ARA70 mediates the suppressive effect of androgen-AR on VDR transactivation.