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

RWDD1 与雄激素受体的配体结合域相互作用,并作为雄激素依赖性转录激活的辅激活因子

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作者:Helga Grötsch, Marlene Kunert, Katrin A Mooslehner, Zhigang Gao, Dagmar Struve, Ieuan A Hughes, Olaf Hiort, Ralf Werner

Abstract

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.

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