RWDD1 interacts with the ligand binding domain of the androgen receptor and acts as a coactivator of androgen-dependent transactivation

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:358

Article

Groetsch, Helga¹  Kunert, Marlene¹  Mooslehner, Katrin A.²  Gao, Zhigang¹  Struve, Dagmar¹  Hughes, Ieuan A.²  Hiort, Olaf¹  Werner, Ralf¹ 

[1] Med Univ Lubeck, Dept Paediat, Div Paediat Endocrinol & Diabet, D-23538 Lubeck, Germany

[2] Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 0QQ, England

关键词: Androgen receptor;    Coactivator;    RWDD1;    Transcription;    Genital tubercle;    Sexual differentiation;   

DOI  :  10.1016/j.mce.2012.02.020

来源: Elsevier

【 摘 要 】

During embryogenesis, the development of the male genital is dependent on androgens. Their actions are mediated by the androgen receptor (AR), which functions as a transcription factor. To identify AR coregulators that support AR action during the critical time window of androgen-dependent development in the genital tubercle of male mice, we performed yeast two-hybrid screenings with cDNA libraries of genital tubercles from male mouse embryos using human AR as bait. RWD domain containing 1 (RWDD1) was identified as an AR-interacting protein from three independent libraries of the embryonic days E15, E16 and E17. The interaction between the AR and RWDD1 was confirmed in vitro and in vivo and the ligand binding domain of the AR was shown to be sufficient to mediate the interaction. RWDD1 enhanced AR-dependent transactivation in reporter assays with promoters of different complexity and in different cell lines. These results suggest that RWDD1 functions as a coactivator of androgen-dependent transcription. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

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