Affiliation:
1. Department of Physiology, Biomedical Sciences Graduate Program, Graduate Program in Biological Sciences, University of California, San Francisco, San Francisco, California
Abstract
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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
114 articles.
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