A novel genetic system for analysis of co-activators for the N-terminal transactivation function domain of the human androgen receptor.
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.
Takeyama
Ken-Ichi
K
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Ito
Saya
S
Sawatsubashi
Shun
S
Shirode
Yuko
Y
Yamamoto
Ayako
A
Suzuki
Eriko
E
Maki
Akio
A
Yamagata
Kaoru
K
Zhao
Yue
Y
Kouzmenko
Alexandre
A
Tabata
Tetsuya
T
Kato
Shigeaki
S
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
D011944:Receptors, Androgen; D015534:Trans-Activators