title: 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 PIASxalpha. 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taira
authors.forename: Sanae Marta Margarita
authors.initials: SM
authors.lastname: Iguchi-Ariga
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D015513:Oncogene Proteins; D011944:Receptors, Androgen