4.4 Article

Transcriptional Suppression by Transient Recruitment of ARIP4 to Sumoylated Nuclear Receptor Ad4BP/SF-1

Journal

MOLECULAR BIOLOGY OF THE CELL
Volume 20, Issue 19, Pages 4235-4245

Publisher

AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E08-12-1247

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Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan
  2. Fumi Yamamura Memorial Foundation for Female Natural Scientists
  3. Grants-in-Aid for Scientific Research [20114002] Funding Source: KAKEN

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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.

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