The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification
Lee, M.B Lebedeva, L.A Suzawa, M Wadekar, S.A Desclozeaux, M Ingraham, H.A
Lebedeva, L.A
Suzawa, M
Wadekar, S.A
Desclozeaux, M
Ingraham, H.A
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Alternative Title
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 PIASxα 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.
Keywords
cell nucleus receptor, dead box protein dp103, histone deacetylase, liver protein, nuclear receptor DAX 1, receptor activity modifying protein, receptor protein, regulator protein, RNA helicase, steroidogenic factor 1, SUMO protein, unclassified drug, animal cell, article, cell nucleus inclusion body, Cercopithecidae, controlled study, data analysis, down regulation, enzyme activity, gene expression regulation, immunohistochemistry, mammal cell, mutational analysis, nonhuman, priority journal, protein domain, protein function, protein localization, protein modification, protein phosphorylation, protein processing, regulatory mechanism, transcription regulation, transcription termination, Animals, Cell Nucleus, Cercopithecus aethiops, COS Cells, DEAD-box RNA Helicases, DNA-Binding Proteins, Down-Regulation, Genes, Reporter, Homeodomain Proteins, Intracellular Signaling Peptides and Proteins, Ligases, Lysine, Mice, Mutation, Promoter Regions (Genetics), Protein Inhibitors of Activated STAT, Protein Processing, Post-Translational, Receptors, Cytoplasmic and Nuclear, RNA Helicases, Small Ubiquitin-Related Modifier Proteins, SUMO-1 Protein, Transcription Factors, Transcription, Genetic, Ubiquitin-Protein Ligases
Source Title
Molecular and Cellular Biology
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Series/Report No.
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Rights
Attribution 4.0 International
Date
2005
DOI
10.1128/MCB.25.5.1879-1890.2005
Type
Article