Resistance to apoptosis conferred by Cdk inhibitors during myocyte differentiation.
Proliferating murine C2C12 myoblasts can undergo either terminal differentiation or programmed cell death under conditions of mitogen deprivation. Unlike myoblasts, differentiated myotubes were resistant to apoptosis. During myogenesis the appearance of the apoptosis-resistant phenotype was correlated with the induction of the cyclin-dependent kinase (Cdk) inhibitor p21(CIP1) but not with the appearance of myogenin, a marker expressed earlier in differentiation. Forced expression of the Cdk inhibitors p21(CIP1) or p16(INK4A) blocked apoptosis during myocyte differentiation. These data indicate that induction of Cdk inhibitors may serve to protect differentiating myocytes from programmed cell death as well as play a role in establishing the postmitotic state.
Wang
J
J
Division of Cardiovascular Research, St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, MA 02135, USA.
Walsh
K
K
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D018008:Myogenin / Q000096:biosynthesis; D010641:Phenotype; D014162:Transfection
D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; C503801:Myog protein, mouse; D018008:Myogenin; D018844:Cyclin-Dependent Kinases