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.
Mesh Terms:
3T3 Cells, Animals, Cells, Cultured, Gene Silencing, Haplorhini, Humans, Intracellular Signaling Peptides and Proteins, Mice, Oncogene Proteins, Protein Inhibitors of Activated STAT, Proteins, Receptors, Androgen, Transcription, Genetic, Tumor Cells, Cultured
J. Biol. Chem.
Date: Oct. 05, 2001
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