CELL-CYCLE-REGULATED EXPRESSION OF THE MUSCLE DETERMINATION FACTOR MYF5 IN PROLIFERATING MYOBLASTS

Myf5 is the earliest-known muscle-specific factor to be expressed in v ivo and its expression is associated with determination of the myoblas t lineage. In C2 cells, we show by immunocytolocalization that Myf5 di sappears rapidly from cells in which the differentiation program has b een 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 posttranscriptio nal regulation of Myf5 by the cell cycle. Immunoblotting of extracts f rom synchronized cultures reveals that Myf5 undergoes periodic fluctua tions during the cell cycle and is absent from cells blocked early in mitosis by use of nocodazole, The disappearance of Myf5 from mitotic c ells involves proteolytic degradation of a phosphorylated form of Myf5 specific to this phase of the cell cycle, In contrast, MyoD levels ar e not depleted in mitotic C2 cells, The mitotic destruction of Myf5 is the first example of a transcription factor showing cell cycle-regula ted degradation, These results may be significant in view of the possi ble role of Myf5 in maintaining the determination of proliferating cel ls and in timing the onset of differentiation.