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Opposing functions of ATF2 and Fos-like transcription factors in c-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts

Oncogene volume 20, pages 7998–8008 (2001)Cite this article

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.

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Acknowledgements

We would like to thank Dr M Lemonnier for the gift of β-tropomyosin-CAT reporter plasmid, Dr F Pons for the gift of connectin antibody, Dr C Dechesne for the gift of probes for chicken myoD and myogenin and Dr Schmidt for the gift of −131/+40 avian myogenin-CAT reporter plasmid. This work was supported by grants from the Institut National de la Recherche Agronomique (INRA), Association pour la Recherche sur le Cancer (ARC), Ligue contre le cancer and Association Française contre les Myopathies (AFM). Laetitia Daury is recipient of fellowships from the Ligue Départemental contre le Cancer and the Association pour la Recherche sur le Cancer and Muriel Busson from the Ministère de la Recherche et de l'Enseignement.

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Authors and Affiliations

  1. Unité d'Endocrinologie Cellulaire, UMR Différenciation Cellulaire et Croissance, Institut National de la Recherche Agronomique (INRA), 2 place Viala, 34060 Montpellier Cedex 1, France

    Laetitia Daury, Muriel Busson, Nikolaï Tourkine, François Casas, Isabelle Cassar-Malek, Chantal Wrutniak-Cabello & Gérard Cabello

  2. Unité de Virologie Humaine, Institut National de la Santé et de la Recherche Médicale (INSERM U412), Ecole Normale Supérieure, 46 allée d'Italie, 69364 Lyon Cedex 07, France

    Marc Castellazzi

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  1. Laetitia Daury
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Correspondence to Chantal Wrutniak-Cabello.

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Daury, L., Busson, M., Tourkine, N. et al. Opposing functions of ATF2 and Fos-like transcription factors in c-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts. Oncogene 20, 7998–8008 (2001). https://doi.org/10.1038/sj.onc.1204967

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