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.
Ogawa
Hidesato
H
Division of Sex Differentiation, National Institute for Basic Biology, National Institutes of Natural Sciences, Myodaiji-cho, Okazaki 444-8787, Japan. hidesato@po.nict.go.jp
Komatsu
Tomoko
T
Hiraoka
Yasushi
Y
Morohashi
Ken-Ichirou
K
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025842:SUMO-1 Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C515057:NR5A1 protein, human; D025842:SUMO-1 Protein; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C546908:RAD54L2 protein, human
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