Abstract
Structural analysis of nuclear receptor subfamily V orphan nuclear receptors suggests that ligand-independent mechanisms must regulate this subclass of receptors. Here, we report that steroidogenic factor 1 (SF-1) and liver receptor homolog 1 are repressed via posttranslational SUMO modification at conserved lysines within the hinge domain. Indeed, mutating these lysines or adding the SUMO isopeptidase SENP1 dramatically increased both native and Gal4-chimera receptor activities. The mechanism by which SUMO conjugation attenuates SF-1 activity was found to be largely histone deacetylase independent and was unaffected by the AF2 corepressor Dax1. Instead, our data suggest that SUMO-mediated repression involves direct interaction of the DEAD-box protein DP103 with sumoylated SF-1. Of potential E3-SUMO ligase candidates, PIASy and PIASxalpha strongly promoted SF-1 sumoylation, and addition of DP103 enhanced both PIAS-dependent receptor sumoylation and SF-1 relocalization to discrete nuclear bodies. Taken together, we propose that DEAD-box RNA helicases are directly coupled to transcriptional repression by protein sumoylation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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COS Cells
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Cell Nucleus / chemistry
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Cell Nucleus / metabolism
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Chlorocebus aethiops
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DEAD Box Protein 20
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DEAD-box RNA Helicases
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation / physiology*
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Genes, Reporter / genetics
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins / physiology
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Ligases / physiology
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Lysine / genetics
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Mice
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Mutation / genetics
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Promoter Regions, Genetic / genetics
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Protein Inhibitors of Activated STAT
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Protein Processing, Post-Translational
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RNA Helicases / analysis
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RNA Helicases / metabolism
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RNA Helicases / physiology*
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Receptors, Cytoplasmic and Nuclear / analysis
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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SUMO-1 Protein / physiology*
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Small Ubiquitin-Related Modifier Proteins / physiology
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Steroidogenic Factor 1
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
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Ubiquitin-Protein Ligases
Substances
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DNA-Binding Proteins
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Nr5a2 protein, mouse
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Piasy protein, mouse
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Protein Inhibitors of Activated STAT
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Receptors, Cytoplasmic and Nuclear
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SUMO-1 Protein
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Small Ubiquitin-Related Modifier Proteins
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Steroidogenic Factor 1
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Transcription Factors
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steroidogenic factor 1, mouse
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Ubiquitin-Protein Ligases
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DEAD Box Protein 20
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Ddx20 protein, mouse
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DEAD-box RNA Helicases
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RNA Helicases
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Ligases
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Pias2 protein, mouse
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Lysine