First Author | Takahashi K | Year | 2001 |
Journal | J Biol Chem | Volume | 276 |
Issue | 40 | Pages | 37556-63 |
PubMed ID | 11477070 | Mgi Jnum | J:213908 |
Mgi Id | MGI:5586804 | Doi | 10.1074/jbc.M101730200 |
Citation | Takahashi K, et al. (2001) DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor. J Biol Chem 276(40):37556-63 |
abstractText | 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. |