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  • Original Paper
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Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation

Abstract

The btg1 (B-cell translocation gene 1) gene coding sequence was isolated from a translocation break point in a case of B-cell chronic lymphocytic leukaemia. We have already shown that BTG1, considered as an antiproliferative protein, strongly stimulates myoblast differentiation. However, the mechanisms involved in this influence remained unknown. In cultured myoblasts, we found that BTG1 stimulates the transcriptional activity of nuclear receptors (T3 and all-trans retinoic acid receptors but not RXRα and PPARγ), c-Jun and myogenic factors (CMD1, Myf5, myogenin). Immunoprecipitation experiments performed in cells or using in vitro-synthesized proteins and GST pull-down assays established that BTG1 directly interacts with T3 and all-trans retinoic acid receptors and with avian MyoD (CMD1). These interactions are mediated by the transactivation domain of each transcription factor and the A box and C-terminal part of BTG1. NCoR presence induces the ligand dependency of the interaction with nuclear receptors. Lastly, deletion of BTG1 interacting domains abrogates its ability to stimulate nuclear receptors and CMD1 activity, and its myogenic influence. In conclusion, BTG1 is a novel important coactivator involved in the regulation of myoblast differentiation. It not only stimulates the activity of myogenic factors, but also of nuclear receptors already known as positive myogenic regulators.

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Acknowledgements

We are grateful to Dr Samarut, Dr Flamant (ENS Lyon, France), Pr P Chambon (LGME Strasbourg, France), Dr PK Vogt (The Scripps Institute, La Jolla, CA), Dr D Montaras (Institut Pasteur, Paris, France), Dr C Deschene (INSERM Nice, France), Dr PB Antin and Dr CP Ordhal (San Francisco, California), Dr LJ De Groot (Chicago, Illinois), Pr BM Paterson (University of Washington, Seattle) and Dr F Pons (INSERM Montpellier, France) for the gift of plasmids, the QM7 myoblast line and the antibodies α17, anti-CMD1, anti-connectin and anti-myosin. This work was supported by INRA (Institut National de Recherche Agronomique), grants from AFM (Association Française pour la recherche contre les Myopathies) and ARC (Association pour la Recherche contre le Cancer). Muriel Busson is a recipient of fellowships from MNRT (Ministère de la Recherche) and ARC.

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Correspondence to Gérard Cabello.

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Busson, M., Carazo, A., Seyer, P. et al. Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation. Oncogene 24, 1698–1710 (2005). https://doi.org/10.1038/sj.onc.1208373

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