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  • Original Paper
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Identification of functional domains involved in BTG1 cell localization

Oncogene volume 20, pages 2691–2703 (2001)Cite this article

Abstract

We have previously shown that BTG1 stimulates myoblast differentiation. In addition, this protein displays a major nuclear localization in confluent myoblasts, decreasing during the early steps of differentiation, and is essentially detected in the cytoplasm of mature myotubes. To identify the domains involved in the cellular trafficking of BTG1, we observed the localization of several BTG1 sequences fused to βGalactosidase. The highly conserved B box among all members of the BTG family induces a significant nuclear localization of the βGal moiety, enhanced by presence of the BTG1 carboxy-terminal sequence. In addition, a functional Nuclear Export Signal (NES) overlaps the B box. Moreover, presence of the first 43 NH2-terminal amino acids reduced the nuclear localization of each chimeric protein tested. Last, the BTG1 amino-terminal domain bears an LxxLL motif favouring nuclear accumulation, and another region encompassing the A box inhibiting nuclear localization. In contrast to a BTG1 mutant exclusively localized in the cytoplasm, transient expression of a mutant displaying a nuclear localization enhanced myoblasts withdrawal from the cell cycle and terminal differentiation, thus mimicking the myogenic influence of BTG1. In conclusion, several regions of BTG1 are implicated in its cellular localization, and BTG1 myogenic activity is induced at the nuclear level.

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Acknowledgements

The authors thank Dr Barbara Wolff-Winiski (Novartis, Vienna, Austria) for the gift of Leptomycin B. This work was supported by grants from I.N.R.A. (Institut National de Recherche Agronomique), A.F.M. (Association Française pour la recherche contre les Myopathies), A.R.C. (Association pour la Recherche contre le Cancer), Ligue de recherche contre le cancer and région Rhône-Alpes. A Rodier, P Rochard, F Casas and L Daury were supported by fellowships from Ligue Nationale de recherche contre le cancer, Fondation pour la Recherche Médicale, I.N.R.A., Ligue Départementale de l'Hérault contre le cancer, respectively.

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Authors and Affiliations

  1. UMR Différenciation Cellulaire et Croissance (INRA, Université Montpellier II, ENSAM), Unité d'Endocrinologie Cellulaire, INRA, 2 place Viala, Montpellier, Cedex 1, 34060, France

    A Rodier, P Rochard, F Casas, L Daury, M Busson, C Wrutniak-Cabello & G Cabello

  2. Unité INSERM U453, Centre Léon Bérard, Lyon, Cedex 08, 69373, France

    C Berthet, J P Rouault & J P Magaud

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  1. A Rodier
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Rodier, A., Rochard, P., Berthet, C. et al. Identification of functional domains involved in BTG1 cell localization. Oncogene 20, 2691–2703 (2001). https://doi.org/10.1038/sj.onc.1204398

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