INHIBITION OF MYOGENIC DIFFERENTIATION IN PROLIFERATING MYOBLASTS BY CYCLIN D1-DEPENDENT KINASE

Although the myogenic regulator MyoD is expressed in proliferating myo blasts, differentiation of these cells is limited to the G(0) phase of the cell cycle. Forced expression of cyclin D1, but not cyclins A, B, or E, inhibited the ability of MyoD to transactivate muscle-specific genes and correlated with phosphorylation of MyoD. Transfection of myo blasts with cyclin-dependent kinase (Cdk) inhibitors p21 and p16 augme nted muscle-specific gene expression in cells maintained in high conce ntrations of serum, suggesting that an active cyclin-Cdk complex suppr esses MyoD function in proliferating cells.