Document Detail


Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif.
MedLine Citation:
PMID:  18063693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interplay between different posttranslational modifications of transcription factors is an important mechanism to achieve an integrated regulation of gene expression. For the estrogen-related receptors (ERRs) alpha and gamma, regulation by posttranslational modifications is still poorly documented. Here we show that transcriptional repression associated with the ERR amino-terminal domains is mediated through sumoylation at a conserved phospho-sumoyl switch, psiKxEPxSP, that exists within a larger synergy control motif. Arginine substitution of the sumoylatable lysine residue or alanine substitution of a nearby phosphorylatable serine residue (serine 19 in ERRalpha) increased the transcriptional activity of both ERRalpha and -gamma. In addition, phospho-mimetic substitution of the serine residue with aspartate restored the sumoylation and transcriptional repression activity. The increased transcriptional activity of the sumoylation-deficient mutants was more pronounced in the presence of multiple adjacent ERR response elements. We also identified protein inhibitor of activated signal transducer and activator of transcription y as an interacting partner and a small ubiquitin-related modifier E3 ligase for ERRalpha. Importantly, analysis with a phospho-specific antibody revealed that sumoylation of ERRalpha in mouse liver requires phosphorylation of serine 19. Taken together, these results show that the interplay of phosphorylation and sumoylation in the amino-terminal domain provides an additional mechanism to regulate the transcriptional activity of ERRalpha and -gamma.
Authors:
Annie M Tremblay; Brian J Wilson; Xiang-Jiao Yang; Vincent Giguère
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-06
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  22     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-26     Completed Date:  2008-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  570-84     Citation Subset:  IM    
Affiliation:
Molecular Oncology Group, McGill University Health Centre, 687 Pine Avenue West, Montréal, Québec, Canada H3A 1A1.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Amino Acid Sequence
Animals
Binding Sites
COS Cells
Cercopithecus aethiops
DNA / chemistry,  genetics
Electrophoretic Mobility Shift Assay
Gene Expression Regulation / physiology*
Hela Cells
Humans
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Mutagenesis, Site-Directed
Phosphorylation
Protein Inhibitors of Activated STAT / physiology
Receptors, Cytoplasmic and Nuclear / genetics*,  metabolism
Receptors, Estrogen / genetics*,  metabolism
Small Ubiquitin-Related Modifier Proteins / genetics,  physiology*
Transcription, Genetic
Chemical
Reg. No./Substance:
0/ERRalpha estrogen-related receptor; 0/ESRRG protein, human; 0/PIAS4 protein, human; 0/Protein Inhibitors of Activated STAT; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Estrogen; 0/Small Ubiquitin-Related Modifier Proteins; 9007-49-2/DNA

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