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J. Cell Biol.,
Volume 140, Number 1, January 12, 1998 111-118
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.
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