Inhibition of Myogenic Differentiation in Proliferating Myoblasts by Cyclin D1-Dependent Kinase

• Published in: Science (American Association for the Advancement of Science) Vol. 267; no. 5200; pp. 1022 - 1024
• Main Authors: Skapek, Stephen X., Rhee, James, Spicer, Douglas B., Lassar, Andrew B.
• Format: Journal Article
• Language: English
• Published: United States American Society for the Advancement of Science 17.02.1995; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Blasts; Carrier Proteins - biosynthesis; Carrier Proteins - physiology; Cell Cycle; Cell Differentiation; Cell Line; Cell proliferation; Cellular biology; Cultured cells; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinases - metabolism; Cyclins; Cyclins - biosynthesis; Cyclins - physiology; Enzyme Activation; Genes; Individualized Instruction; Inhibition; Mice; Muscle cells; Muscle fibers; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscular system; Myoblasts; MyoD Protein - antagonists & inhibitors; MyoD Protein - metabolism; Oncogene Proteins - physiology; Phosphorylation; Physiological aspects; Plasmids; Proteins; Transcriptional Activation; Transfection; Vehicles
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7863328

Although the myogenic regulator MyoD is expressed in proliferating myoblasts, 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 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.