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Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus.

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR(153-336), containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR(153-336) fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.

Pubmed ID: 11854421

Authors

  • Markus SM
  • Taneja SS
  • Logan SK
  • Li W
  • Ha S
  • Hittelman AB
  • Rogatsky I
  • Garabedian MJ

Journal

Molecular biology of the cell

Publication Data

February 20, 2002

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 2T32 GM-07308
  • Agency: NIAID NIH HHS, Id: 5T32 AI-07180
  • Agency: NIDDK NIH HHS, Id: K08 DK-02577
  • Agency: NCI NIH HHS, Id: P30 CA-16087
  • Agency: NIDDK NIH HHS, Id: R01 DK-58024
  • Agency: NIDDK NIH HHS, Id: T32 DK-07775

Mesh Terms

  • Amino Acid Sequence
  • Gene Expression Regulation
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Receptors, Androgen
  • Trans-Activators
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques