Document Detail


SUMOylation of Pax7 is essential for neural crest and muscle development.
MedLine Citation:
PMID:  23247248     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Regulatory transcription factors of the Pax family play fundamental roles in the function of multipotent cells during vertebrate development, post-natal regeneration, and cancer. Pax7 and its homologue Pax3 are important players in neural crest and muscle development. Both genes are coexpressed in various tissues and are thought to provide similar, but not identical, functions. The mechanisms that allow specific regulation of Pax7 remain largely unknown. Here, we report for the first time that Pax7 is regulated by SUMOylation. We identify the interaction of Pax7 with Ubc9, the SUMO conjugating enzyme, and reveal that SUMOylation machinery is enriched in neural crest precursors and plays a critical role in NC development. We demonstrate that Pax7 becomes SUMOylated and identify an essential role for lysine 85 (K85) in Pax7-SUMOylation. Despite high conservation surrounding K85 amongst Pax genes, we were unable to identify SUMOylation of other Pax proteins tested, including Pax3. Using a non-SUMOylatable Pax7 variant (K85 X R), we demonstrate that SUMOylation is essential for the function of Pax7 in neural crest development, C2C12 myogenic differentiation, and transcriptional transactivation. Our study provides new mechanistic insight into the molecular regulation of Pax7's function by SUMOylation in neural crest and muscle development.
Authors:
Zhidong Luan; Ying Liu; Timothy J Stuhlmiller; Jonathan Marquez; Martín I García-Castro
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-18
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  70     ISSN:  1420-9071     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-23     Completed Date:  2013-06-18     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1793-806     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cell Differentiation
Cell Line
Chick Embryo
Chickens
HEK293 Cells
Humans
Mice
Molecular Sequence Data
Muscle Development
Mutagenesis, Site-Directed
Myoblasts / cytology,  metabolism
Neural Crest / metabolism*
PAX7 Transcription Factor / chemistry,  genetics,  metabolism*
Paired Box Transcription Factors / metabolism
Protein Binding
SUMO-1 Protein / genetics,  metabolism
Sequence Alignment
Sumoylation
Transfection
Ubiquitin-Conjugating Enzymes / metabolism
Grant Support
ID/Acronym/Agency:
R01 DE017914/DE/NIDCR NIH HHS; R01DE017914/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/PAX3 protein, human; 0/PAX7 Transcription Factor; 0/PAX7 protein, human; 0/Paired Box Transcription Factors; 0/SUMO-1 Protein; 0/SUMO1 protein, human; EC 6.3.2.19/Ubiquitin-Conjugating Enzymes; EC 6.3.2.19/ubiquitin-conjugating enzyme UBC9
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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