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

J Biol Chem. 2001 Oct 5;276(40):37556-63. doi: 10.1074/jbc.M101730200. Epub 2001 Jul 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cells, Cultured
  • Gene Silencing
  • Haplorhini
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Oncogene Proteins / metabolism*
  • Protein Deglycase DJ-1
  • Protein Inhibitors of Activated STAT
  • Proteins / metabolism*
  • Proteins / physiology
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Transcription, Genetic / physiology
  • Tumor Cells, Cultured

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Pias1 protein, mouse
  • Protein Inhibitors of Activated STAT
  • Proteins
  • Receptors, Androgen
  • PARK7 protein, human
  • Protein Deglycase DJ-1