Novel ATPase of SNF2-like protein family interacts with androgen receptor and modulates androgen-dependent transcription

Mol Biol Cell. 2002 Jun;13(6):2106-19. doi: 10.1091/mbc.01-10-0484.


Nuclear receptors, including the androgen receptor (AR), regulate target cell transcription through interaction with auxiliary proteins to modify chromatin structure. We describe herein a novel AR-interacting protein, termed ARIP4, that has structural features typical of the SNF2-like protein family. With regard to the Snf2 domain, the closest homolog of ARIP4 is the ATRX protein. ARIP4 is a nuclear protein and comprises 1466 amino acids. It interacts with AR in vitro and in cultured yeast and mammalian cells. ARIP4 can be labeled with 8-azido-[gamma-32P]ATP and exhibits DNA-dependent ATPase activity. Like several ATP-dependent chromatin remodeling proteins, ARIP4 generates superhelical torsion within linear DNA fragments in an ATP-dependent manner. With a stably integrated target promoter, ARIP4 elicits a modest enhancement of AR-dependent transactivation. In transient cotransfection assays, ARIP4 modulates AR function in a promoter-dependent manner; it enhances receptor activity on minimal promoters, but does not activate more complex promoters. ARIP4 mutants devoid of ATPase activity fail to alter DNA topology and behave as trans-dominant negative regulators of AR function in transient assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics
  • COS Cells
  • Chlorocebus aethiops
  • DNA, Complementary
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology*
  • Genes, Reporter
  • Insecta
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Receptors, Androgen / metabolism*
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins
  • Sequence Alignment
  • Serine Endopeptidases / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection
  • beta-Galactosidase / genetics


  • Bacterial Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • LexA protein, Bacteria
  • Nuclear Proteins
  • Receptors, Androgen
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphate
  • beta-Galactosidase
  • Serine Endopeptidases
  • Adenosine Triphosphatases
  • SNF2 protein, S cerevisiae