Transcriptional Suppression by Transient Recruitment of ARIP4 to Sumoylated nuclear receptor Ad4BP/SF-1

Mol Biol Cell. 2009 Oct;20(19):4235-45. doi: 10.1091/mbc.e08-12-1247. Epub 2009 Aug 19.

Abstract

The small ubiquitin-like modifier SUMO conjugates transcription factors and suppresses their respective activation of target genes. Although various SUMO-modified transcription factors have been isolated, mechanisms whereby sumoylated-substrates modulate transcription remain unknown. Here, we purified ARIP4 (AR interacting protein 4, a Rad54 family member and a SNF2 chromatin remodeling factor), which interacts with sumoylated Ad4BP/SF-1 through two SUMO-interacting motifs and one Ad4BP/SF-1-binding region. Remarkably, ARIP4 also interacts selectively with other sumoylated nuclear receptors including LRH-1, AR, and GR. Interestingly, the ATPase activity of ARIP4 was stimulated in the presence of sumoylated Ad4BP/SF-1 and the Ad4BP/SF-1-binding site containing double-stranded DNA. ChIP assays and siRNA studies strongly suggested that ARIP4 temporally suppresses Ad4BP/SF-1-mediated transcription through its transient recruitment to target genes. These findings suggest that ARIP4 may be a cofactor that modulates SUMO-mediated fine-tuning of transcriptional suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Sequence
  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA Helicases
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Molecular Sequence Data
  • Protein Binding
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • SUMO-1 Protein / metabolism*
  • Sequence Homology, Amino Acid
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • NR5A1 protein, human
  • SUMO-1 Protein
  • Steroidogenic Factor 1
  • Transcription Factors
  • Adenosine Triphosphatases
  • DNA Helicases
  • RAD54L2 protein, human