Cloning and functional characterization of a rat Daxx that functions as a corepressor for the androgen receptor.
The androgen receptor (AR), a ligand-activated nuclear transcription factor, plays an important role in endocrine system development and homeostasis. AR-mediated gene transcription is modulated by a wide variety of coregulator proteins, but corepressors of AR have not been well characterized. We have isolated a rat homologue of Daxx, a possible AR repressor. The clone obtained comprised a 2196 bp open reading frame, corresponding to a sequence of 731 amino acids with 80.5% homology to mouse. Basal transcription of the isolated clone was repressed in transient transcription experiments using a Gal4 reporter gene assay. Furthermore, a mammalian two-hybrid assay showed a strong interaction between Daxx and promyelocytic leukemia (PML) protein. These results indicate that the isolated clone is a rat homologue of Daxx. The rat Daxx (rDaxx) interacted with the androgen receptor (AR): in co-immunoprecipitation experiments, AR formed complexes with anti-Daxx antibody. Furthermore, overexpression of Daxx suppressed AR-mediated transcriptional activity in HeLa and CV1 cells in transient transfection experiments. Taken together, our results suggest that Daxx may function as a corepressor for the androgen receptor.
Mizuta
Haruo
H
Department of Internal Medicine, Division of Neurology, Saga University, Faculty of Medicine, Saga 849-8501, Japan. mizutah@med.saga-u.ac.jp
Kuroda
Yasuo
Y
D000595:Amino Acid Sequence; D059002:Androgen Receptor Antagonists; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D056970:Co-Repressor Proteins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
D059002:Androgen Receptor Antagonists; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D012097:Repressor Proteins