© The Rockefeller University Press,
0021-9525/1998//111 $5.00
The Journal of Cell Biology, Volume 140, Number 1,
, 1998 111-118
Cell Cycle–regulated Expression of the Muscle Determination Factor Myf5 in Proliferating Myoblasts
Catherine Lindon,
Didier Montarras, and
Christian Pinset
Groupe de Développement Cellulaire, Institut Pasteur, Département de Biologie Moléculaire, 75724 Paris Cedex 15
Myf5 is the earliest-known muscle-specific factor to be expressed in vivo and its expression is associated with determination of the myoblast lineage. In C2 cells, we show by immunocytolocalization that Myf5 disappears rapidly from cells in which the differentiation program has been initiated. In proliferating myoblasts, the levels of Myf5 and MyoD detected from cell to cell are very heterogeneous. We find that some of the heterogeneity of Myf5 expression arises from a posttranscriptional regulation of Myf5 by the cell cycle. Immunoblotting of extracts from synchronized cultures reveals that Myf5 undergoes periodic fluctuations during the cell cycle and is absent from cells blocked early in mitosis by use of nocodazole. The disappearance of Myf5 from mitotic cells involves proteolytic degradation of a phosphorylated form of Myf5 specific to this phase of the cell cycle. In contrast, MyoD levels are not depleted in mitotic C2 cells. The mitotic destruction of Myf5 is the first example of a transcription factor showing cell cycle–regulated degradation. These results may be significant in view of the possible role of Myf5 in maintaining the determination of proliferating cells and in timing the onset of differentiation.
Abbreviations used in this paper: ALLN, N-acetyl-Leu-Leu-norleucinal; cdk, cyclin-dependent kinase; IGF, insulin-like growth factor; MRF, myogenic regulatory factors; RIPA, radioimmunoprecipitation assay.
C. Lindon is the recipient of a bourse d'étude from the Fondation Simone et Cino del Duca. The Groupe de Développement Cellulaire is funded by the Institut Pasteur, the Centre National de la Recherche Scientifique, and the Association Française contre les Myopathies.
Address all correspondence to C. Lindon, Groupe de Développement Cellulaire, Institut Pasteur, Département de Biologie Moléculaire, 25 rue du Dr Roux, 75724 Paris Cedex 15. Tel.: (33) 1-45-68-84-76. Fax: (33) 1-45-68-89-63. E-mail: clindon{at}pasteur.fr

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