The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification

Mol Cell Biol. 2005 Mar;25(5):1879-90. doi: 10.1128/MCB.25.5.1879-1890.2005.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • DEAD Box Protein 20
  • DEAD-box RNA Helicases
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / physiology*
  • Genes, Reporter / genetics
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins / physiology
  • Ligases / physiology
  • Lysine / genetics
  • Mice
  • Mutation / genetics
  • Promoter Regions, Genetic / genetics
  • Protein Inhibitors of Activated STAT
  • Protein Processing, Post-Translational
  • RNA Helicases / analysis
  • RNA Helicases / metabolism
  • RNA Helicases / physiology*
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • SUMO-1 Protein / physiology*
  • Small Ubiquitin-Related Modifier Proteins / physiology
  • Steroidogenic Factor 1
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Ubiquitin-Protein Ligases

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nr5a2 protein, mouse
  • Piasy protein, mouse
  • Protein Inhibitors of Activated STAT
  • Receptors, Cytoplasmic and Nuclear
  • SUMO-1 Protein
  • Small Ubiquitin-Related Modifier Proteins
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, mouse
  • Ubiquitin-Protein Ligases
  • DEAD Box Protein 20
  • Ddx20 protein, mouse
  • DEAD-box RNA Helicases
  • RNA Helicases
  • Ligases
  • Pias2 protein, mouse
  • Lysine