DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex.
DJ-1 was identified by us as a novel oncogene that transforms mouse NIH3T3 cells in cooperation with ras. We later identified PIAS (protein inhibitor of activated STAT)xalpha as a DJ-1-binding protein, and found that DJ-1 restored androgen receptor (AR) transcription activity that was repressed by PIASxalpha. To further characterize the function of DJ-1, we cloned cDNA encoding a novel DJ-1-binding protein, DJBP, by a yeast two-hybrid system. DJBP mRNA was found to be specifically expressed in the testis. In addition to the binding of DJBP to the COOH-terminal region of DJ-1, DJBP was also found to bind in vitro and in vivo to the DNA-binding domain of the AR in a testosterone-dependent manner and to be colocalized with DJ-1 or AR in the nucleus. Furthermore, a co-immunoprecipitation assay showed that the formation of a ternary complex between DJ-1, DJBP, and AR occurred in cells in which DJ-1 bound to the AR via DJBP. It was found that DJBP repressed a testosterone-dependent AR transactivation activity in monkey Cos1 cells by recruiting histone deacetylase (HDAC) complex, including HDAC1 and mSin3, and that DJ-1 partially restored its repressed activity by abrogating DJBP-HDAC complex. These results suggest that AR is positively regulated by DJ-1, which antagonizes the function of negative regulators, including DJBP.
Niki
Takeshi
T
Graduate School of Pharmaceutical Sciences and College of Medical Technology, Hokkaido University, Kita-ku, Sapporo, Japan.
Takahashi-Niki
Kazuko
K
Taira
Takahiro
T
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D015723:Gene Library; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D012097:Repressor Proteins; D015533:Transcriptional Activation; D014162:Transfection
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C481388:EFCAB6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D012097:Repressor Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D006655:Histone Deacetylases