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.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cell Line, Cloning, Molecular, Gene Expression Profiling, Gene Library, Histone Deacetylases, Humans, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Multienzyme Complexes, Oncogene Proteins, Organ Specificity, Protein Binding, RNA, Messenger, Receptors, Androgen, Transcriptional Activation, Transfection
Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cell Line, Cloning, Molecular, Gene Expression Profiling, Gene Library, Histone Deacetylases, Humans, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Multienzyme Complexes, Oncogene Proteins, Organ Specificity, Protein Binding, RNA, Messenger, Receptors, Androgen, Transcriptional Activation, Transfection
Mol. Cancer Res.
Date: Feb. 01, 2003
PubMed ID: 12612053
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