Co-localization with DJ-1 is essential for the androgen receptor to exert its transcription activity that has been impaired by androgen antagonists

Abstract

DJ-1 was first identified as a novel candidate of an oncogene product in cooperation with an activated ras, and DJ-1 was later found to be a positive regulator of the androgen receptor (AR) transcription activity that was repressed by PIASxα. 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 roles of DJ-1 in the AR function, the effects of several androgen antagonists, some of which had been identified as endocrine-disrupting chemicals, on AR transcription activity and localization of AR and DJ-1 in Cos7 cells were examined. Co-localization of DJ-1 with the AR as dot-like spots in the nucleus was first found in cells that had not been treated with chemicals. Although all of the chemicals tested inhibited AR transcription activity to an average of 25% of that without chemicals, there were two classes affecting the localization of the two proteins; one changes the AR from dot-like spots to diffuse spaces in the nucleus and the other still keeps the AR in the dot-like spots. The localization of DJ-1, on the other hand, was found to be dramatically changed by all of the chemicals, resulting in loss of co-localization with the AR. These results indicate that DJ-1 is an essential factor for the AR to exert its full activity. © 2004 Pharmaceutical Society of Japan.