title: Opposing functions of ATF2 and Fos-like transcription factors in c-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts.
abstract: With the aim to identify the oncoprotein partners implicated in the c-Jun myogenic influence, we carried out stable transfection experiments of c-Jun and/or ATF2, Fra2, c-Fos overexpression in avian myoblasts. Before induction of differentiation, c-Jun repressed myoblast withdrawal from the cell cycle, as did a TPA treatment. However, after serum removal, unlike TPA, c-Jun significantly stimulated myoblast differentiation. In search for specific partners involved in this dual influence, we found that a reduction in the amounts of c-Fos and Fra2 and an increase in c-Jun proteins occurred at cell confluence, a situation likely to favor cooperation between c-Jun and ATF2 during terminal differentiation. Whereas c-Fos and Fra2 cooperated with c-Jun to abrogate myoblast withdrawal from the cell cycle and terminal differentiation, ATF2 co-expression potentiated the positive myogenic c-Jun influence. In addition, myogenin expression was a positive target of this cooperation and this regulation occurred through a stimulation of myogenin promoter activity: (1) whereas c-Fos or Fra2 co-expression abrogated c-Jun stimulatory activity on this promoter, ATF2 co-expression potentiated this influence; (2) using a dominant negative ATF2 mutant, we established that c-Jun transcriptional activity required functionality of endogenous ATF2. These data suggest that through this dual myogenic influence due to cooperations with different partners, c-Jun is involved in the control of duration of myoblast proliferation and thereafter of fusion efficiency.
authors.affiliation: Unité d'Endocrinologie Cellulaire, UMR Différenciation Cellulaire et Croissance, Institut National de la Recherche Agronomique (INRA), 2 place Viala, 34060 Montpellier Cedex 1, France.
authors.forename: L
authors.initials: L
authors.lastname: Daury
authors.forename: M
authors.initials: M
authors.lastname: Busson
authors.forename: N
authors.initials: N
authors.lastname: Tourkine
authors.forename: F
authors.initials: F
authors.lastname: Casas
authors.forename: I
authors.initials: I
authors.lastname: Cassar-Malek
authors.forename: C
authors.initials: C
authors.lastname: Wrutniak-Cabello
authors.forename: M
authors.initials: M
authors.lastname: Castellazzi
authors.forename: G
authors.initials: G
authors.lastname: Cabello
mesh_terms: D051698:Activating Transcription Factor 2; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D051921:Fos-Related Antigen-2; D005799:Genes, Dominant; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D009154:Mutation; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011784:Quail; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; D018008:Myogenin; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors