Composition and Function of AP-1 Transcription Complexes during Muscle Cell Differentiation

The role of activating protein-1 (AP-1) in muscle cells is currently equivocal. While some studies propose that AP-1 is inhibitory for myogenesis, others implicate a positive role in this process. We tested whether this variation may be due to different properties of the AP-1 subunit composition in...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 277; no. 19; pp. 16426 - 16432
Main Authors:	Andreucci, John J., Grant, Diane, Cox, David M., Tomc, Lyn K., Prywes, Ron, Goldhamer, David J., Rodrigues, Natalie, Bédard, Pierre-André, McDermott, John C.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 10-05-2002 American Society for Biochemistry and Molecular Biology
Subjects:	Animals AP-1 protein Blotting, Western Cell Differentiation Cell Division Cells, Cultured COS Cells DNA-Binding Proteins - metabolism Fos-Related Antigen-2 Fra-2 protein Genes, Reporter HeLa Cells Humans Immunoblotting JunD protein Luciferases - metabolism Models, Biological Muscles - cytology Muscles - metabolism myogenesis Phosphorylation Precipitin Tests Promoter Regions, Genetic Protein Binding Protein Isoforms Proto-Oncogene Proteins c-jun - metabolism Time Factors Transcription Factor AP-1 - genetics Transcription Factor AP-1 - physiology Transcription Factors - metabolism Transcription, Genetic Transfection Tre-LUC gene
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Summary:	The role of activating protein-1 (AP-1) in muscle cells is currently equivocal. While some studies propose that AP-1 is inhibitory for myogenesis, others implicate a positive role in this process. We tested whether this variation may be due to different properties of the AP-1 subunit composition in differentiating cells. Using Western analysis we show that c-Jun, Fra-2, and JunD are expressed throughout the time course of differentiation. Phosphatase assays indicate that JunD and Fra-2 are phosphorylated in muscle cells and that at least two isoforms of each are expressed in muscle cells. Electrophoretic mobility shift assays combined with antibody supershifts indicate the appearance of Fra-2 as a major component of the AP-1 DNA binding complex in differentiating cells. In this context it appears that Fra-2 heterodimerizes with c-Jun and JunD. Studying the c-jun enhancer in reporter gene assays we observed that the muscle transcription factors MEF2A and MyoD can contribute to robust transcriptional activation of the c-jun enhancer. In differentiating muscle cells mutation of the MEF2 site reduces transactivation of the c-jun enhancer and MEF2A is the predominant MEF2 isoform binding to this cis element. Transcriptional activation of an AP-1 site containing reporter gene (TRE-Luc) is enhanced under differentiation conditions compared with growth conditions in C2C12 muscle cells. Further studies indicate that Fra-2 containing AP-1 complexes can transactivate the MyoD enhancer/promoter. Thus, an AP-1 complex containing Fra-2 and c-Jun or JunD is consistent with muscle differentiation, indicating that AP-1 function during myogenesis is dependent on its subunit composition.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.M110891200