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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.

Pubmed ID: 12612053

Authors

  • Niki T
  • Takahashi-Niki K
  • Taira T
  • Iguchi-Ariga SM
  • Ariga H

Journal

Molecular cancer research : MCR

Publication Data

February 3, 2003

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Binding Proteins
  • 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
  • Repressor Proteins
  • Transcriptional Activation
  • Transfection