The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification.
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.
Lee
Martin B
MB
Department of Physiology, Biomedical Sciences Graduate Program, Graduate Program in Biological Sciences, Mission Bay Campus, University of California, San Francisco, Box 0444, San Francisco, CA 94143-2611, USA.
Lebedeva
Lioudmila A
LA
Suzawa
Miyuki
M
Wadekar
Subhagya A
SA
Desclozeaux
Marion
M
Ingraham
Holly A
HA
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002522:Chlorocebus aethiops; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008025:Ligases / Q000502:physiology; D008239:Lysine / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D050828:Protein Inhibitors of Activated STAT; D011499:Protein Processing, Post-Translational; D020365:RNA Helicases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C431936:Nr5a2 protein, mouse; C414349:Piasy protein, mouse; D050828:Protein Inhibitors of Activated STAT; D018160:Receptors, Cytoplasmic and Nuclear; D025842:SUMO-1 Protein; D025841:Small Ubiquitin-Related Modifier Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D044767:Ubiquitin-Protein Ligases; D055541:DEAD Box Protein 20; C485624:Ddx20 protein, mouse; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; D008025:Ligases; C476735:Pias2 protein, mouse; D008239:Lysine