title: A novel genetic system for analysis of co-activators for the N-terminal transactivation function domain of the human androgen receptor.
abstract: Androgen receptor (hAR) regulates transcription of target genes in a ligand-dependent manner and recruits a number of co-activators for the ligand-induced transactivation via the N-terminal, activation function-1 (AF-1), and C-terminal, AF-2, transactivation domains. But the co-regulator functions on each of AR domains have not yet been fully understood. We have established a Drosophila transgenic system in which hAR and its deletion mutants are ectopically expressed in fly tissues together with an AR response element (ARE)-GFP reporter gene, and have confirmed that hAR was functional in ARE transactivation without affecting the expression of endogenous genes. We found that transcriptional activity of the hAR AF-1 domain was markedly reduced in Drosophila deficiency mutants of homologs for known mammalian co-activators of the AR ligand-dependent AF-2 domain. This suggests that hAR AF-1 recruits co-activators previously known only to interact with the AF-2 domain. Therefore, Drosophila with the hAR AF-1 transgene provides a relevant genetic system in which to uncover novel functions of vertebrate steroid hormone receptors and to screen for novel AF-1 co-regulators.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.forename: Shun
authors.initials: S
authors.lastname: Sawatsubashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirode
authors.forename: Ayako
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Akio
authors.initials: A
authors.lastname: Maki
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamagata
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kouzmenko
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tabata
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D006801:Humans; D008722:Methods; D009154:Mutation; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D011944:Receptors, Androgen; D015534:Trans-Activators