Identification of functional domains involved in BTG1 cell localization

Autor: Cyril Berthet, Muriel Busson, Gérard Cabello, Jean-Pierre Rouault, François Casas, Chantal Wrutniak-Cabello, Jean-Pierre Magaud, P Rochard, L Daury, A Rodier
Přispěvatelé: Différenciation Cellulaire et Croissance (DCC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Instituto de Investigación en Recursos Cinegéticos (IREC), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Zdroj: Oncogene
Oncogene, Nature Publishing Group, 2001, 20, pp.2691-2703
Oncogene, Nature Publishing Group, 2001, 20 (21), pp.2691-2703. ⟨10.1038/sj.onc.1204398⟩
Oncogene, 2001, 20 (21), pp.2691-2703. ⟨10.1038/sj.onc.1204398⟩
ISSN: 0950-9232
1476-5594
DOI: 10.1038/sj.onc.1204398⟩
Popis: 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 betaGalactosidase. The highly conserved B box among all members of the BTG family induces a significant nuclear localization of the betaGal 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 NH(2)-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.
Databáze: OpenAIRE