Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase

Although the myogenic regulator MyoD is expressed in proliferating myoblasts, differentiation of these cells is limited to the G₀ 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 myoblasts with cyclin-dependent kinase (Cdk) inhibitors p21 and p16 augmented muscle-specific gene expression in cells maintained in high concentrations of serum, suggesting that an active cyclin-Cdk complex suppresses MyoD function in proliferating cells.