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

Lee, Martin B., Lebedeva, Lioudmila A., Suzawa, Miyuki, Wadekar, Subhagya A., Desclozeaux, Marion and Ingraham, Holly A. (2005) The DEAD-Box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification. Molecular and cellular biology, 25 5: 1879-1890. doi:10.1128/MCB.25.5.1879-1890.2005

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Author Lee, Martin B.
Lebedeva, Lioudmila A.
Suzawa, Miyuki
Wadekar, Subhagya A.
Desclozeaux, Marion
Ingraham, Holly A.
Title The DEAD-Box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification
Journal name Molecular and cellular biology   Check publisher's open access policy
ISSN 0270-7306
Publication date 2005-03
Sub-type Article (original research)
DOI 10.1128/MCB.25.5.1879-1890.2005
Open Access Status File (Publisher version)
Volume 25
Issue 5
Start page 1879
End page 1890
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
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 PIASx{alpha} 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 90 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 11 Feb 2009, 10:21:04 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience