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J Biol Chem. 2001 Oct 5;276(40):37556-63. Epub 2001 Jul 26.

DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor.

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1
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

Abstract

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.

PMID:
11477070
DOI:
10.1074/jbc.M101730200
[Indexed for MEDLINE]
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