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.
Skapek
S X
SX
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Rhee
J
J
Spicer
D B
DB
Lassar
A B
AB
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D019938:Cyclin D1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000096:biosynthesis / Q000502:physiology*; D004789:Enzyme Activation; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015513:Oncogene Proteins / Q000502:physiology*; D010766:Phosphorylation; D015533:Transcriptional Activation; D014162:Transfection
D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017570:MyoD Protein; D015513:Oncogene Proteins; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases