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

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.

Pubmed ID: 19692572 RIS Download

Mesh terms: Adenosine Triphosphatases | 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 | Sequence Homology, Amino Acid | Steroidogenic Factor 1 | Transcription Factors | Transcription, Genetic

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