DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor.
DJ-1 was first identified as a novel candidate of the oncogene product that transformed mouse NIH3T3 cells in cooperation with an activated ras. Later DJ-1 was also found to be an infertility-related protein that was reduced in rat sperm treated with sperm toxicants that cause infertility in rats. To determine the functions of DJ-1, cDNAs encoding DJ-1-binding proteins were screened by the yeast two-hybrid method. Of several proteins identified, PIASx alpha/ARIP3, a modulator of androgen receptor (AR), was first characterized as the DJ-1-binding protein in this study. DJ-1 directly bound to the AR-binding region of PIASx alpha by an in vitro coimmunoprecipitation assay and also bound to PIASx alpha in human 293T cells. Both proteins were co-localized in the nuclei. PIASx alpha inhibited the AR transcription activity in a dose-dependent manner in cotransfected monkey CV1 cells with an androgen responsive element-luciferase reporter. Introduction of DJ-1 into CV1 cells in a state of inhibition of AR activity by PIASx alpha restored AR transcription activity by absorbing PIASx alpha from the AR-PIASx alpha complex, while a DJ-1 mutant harboring an amino acid substitution at number 130 from lysine to arginine did not restore it. These results indicate that DJ-1 is a positive regulator of the androgen receptor.
Takahashi
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Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Taira
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Niki
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Seino
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Iguchi-Ariga
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Ariga
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D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D020868:Gene Silencing; D000882:Haplorhini; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D011944:Receptors, Androgen; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1