Document Detail


SUMO represses transcriptional activity of the Drosophila SoxNeuro and human Sox3 central nervous system-specific transcription factors.
MedLine Citation:
PMID:  15788563     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sry high mobility group (HMG) box (Sox) transcription factors are involved in the development of central nervous system (CNS) in all metazoans. Little is known on the molecular mechanisms that regulate their transcriptional activity. Covalent posttranslational modification by small ubiquitin-like modifier (SUMO) regulates several nuclear events, including the transcriptional activity of transcription factors. Here, we demonstrate that SoxNeuro, an HMG box-containing transcription factor involved in neuroblast formation in Drosophila, is a substrate for SUMO modification. SUMOylation assays in HeLa cells and Drosophila S2 cells reveal that lysine 439 is the major SUMO acceptor site. The sequence in SoxNeuro targeted for SUMOylation, IKSE, is part of a small inhibitory domain, able to repress in cis the activity of two adjacent transcriptional activation domains. Our data show that SUMO modification represses SoxNeuro transcriptional activity in transfected cells. Overexpression in Drosophila embryos of a SoxN form that cannot be targeted for SUMOylation strongly impairs the development of the CNS, suggesting that SUMO modification of SoxN is crucial for regulating its activity in vivo. Finally, we present evidence that SUMO modification of group B1 Sox factors was conserved during evolution, because Sox3, the human counterpart of SoxN, is also negatively regulated through SUMO modification.
Authors:
Jean Savare; Nathalie Bonneaud; Franck Girard
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-03-23
Journal Detail:
Title:  Molecular biology of the cell     Volume:  16     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-03     Completed Date:  2005-11-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2660-9     Citation Subset:  IM    
Affiliation:
Institut de Génétique Humaine, Centre National de la Recherche Scientifique Unité Propre de Recherche 1142, 34396 Montpellier, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Amino Acid Sequence
Amino Acid Substitution
Animals
Animals, Genetically Modified
Arginine / metabolism
Central Nervous System / embryology*
Conserved Sequence
DNA-Binding Proteins / chemistry,  genetics*
Drosophila / cytology,  embryology*,  genetics
Drosophila Proteins / chemistry,  genetics*
Embryo, Nonmammalian
Evolution, Molecular
Gene Expression Regulation, Developmental*
Genes, Reporter
Hela Cells
High Mobility Group Proteins / chemistry,  genetics*
Humans
Immunohistochemistry
Luciferases / metabolism
Lysine / chemistry
Molecular Sequence Data
Protein Structure, Tertiary
SOX Transcription Factors
SOXB1 Transcription Factors
SUMO-1 Protein / genetics,  metabolism*
Sequence Homology, Amino Acid
Species Specificity
Transcription Factors / chemistry,  genetics*
Transcription, Genetic
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Drosophila Proteins; 0/High Mobility Group Proteins; 0/SOX Transcription Factors; 0/SOX3 protein, human; 0/SOXB1 Transcription Factors; 0/SUMO-1 Protein; 0/SoxNeuro protein, Drosophila; 0/Transcription Factors; 56-87-1/Lysine; 74-79-3/Arginine; EC 1.13.12.-/Luciferases
Comments/Corrections

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