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Molecular and Cellular Biology, March 2005, p. 1879-1890, Vol. 25, No. 5
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.5.1879-1890.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The DEAD-Box Protein DP103 (Ddx20 or Gemin-3) Represses Orphan Nuclear Receptor Activity via SUMO Modification

Martin B. Lee,{dagger} Lioudmila A. Lebedeva,{dagger} Miyuki Suzawa, Subhagya A. Wadekar, Marion Desclozeaux, and Holly A. Ingraham*

Department of Physiology, Biomedical Sciences Graduate Program, Graduate Program in Biological Sciences, University of California, San Francisco, San Francisco, California

Received 16 September 2004/ Returned for modification 18 October 2004/ Accepted 26 November 2004

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.

* Corresponding author. Mailing address: Department of Physiology, Biomedical Sciences Graduate Program, Graduate Program in Biological Sciences, 1550 4th St., GDBS Building, Mission Bay Campus, University of California, San Francisco, Box 0444, San Francisco, CA 94143-2611. Phone: (415) 476-2731. Fax: (415) 514-3792. E-mail: hollyi{at}itsa.ucsf.edu.

{dagger} M.B.L. and L.A.L. contributed equally to this work.

Molecular and Cellular Biology, March 2005, p. 1879-1890, Vol. 25, No. 5
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.5.1879-1890.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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