Correlation of Terminal Cell Cycle Arrest of Skeletal Muscle with Induction of p21 by MyoD

• Published in: Science (American Association for the Advancement of Science) Vol. 267; no. 5200; pp. 1018 - 1021
• Main Authors: Halevy, Orna, Novitch, Bennett G., Spicer, Douglas B., Skapek, Stephen X., Rhee, James, Hannon, Gregory J., Beach, David, Lassar, Andrew B.
• Format: Journal Article
• Language: English
• Published: Washington, DC 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; Antibodies; Biological and medical sciences; Carrier Proteins; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell growth; Cell Line; Cell lines; Cell physiology; Cell proliferation; Cellular biology; Cellular differentiation; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases - antagonists & inhibitors; Cyclins - biosynthesis; Cyclins - genetics; DNA; DNA-Binding Proteins; E2F Transcription Factors; Enzyme inhibitors; Fibroblasts; Fundamental and applied biological sciences. Psychology; Genes; Humans; Individualized Instruction; Logical Thinking; Mice; Microtubule-Associated Proteins - biosynthesis; Microtubule-Associated Proteins - genetics; Molecular and cellular biology; Muscle cells; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscular system; Myoblasts; MyoD Protein - physiology; Physiological aspects; Proteins; Resting Phase, Cell Cycle; Retinoblastoma Protein - physiology; Retinoblastoma-Binding Protein 1; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Skeletal muscle; Transcription Factor DP1; Transcription Factors - metabolism; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - physiology; Tumor Suppressor Proteins; Development; Differentiation; Gene expression; Transcription factor; Striated muscle; Cell cycle
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7863327

Skeletal muscle differentiation entails the coordination of muscle-specific gene expression and terminal withdrawal from the cell cycle. This cell cycle arrest in the G$_0$ phase requires the retinoblastoma tumor suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibitors. Expression of MyoD, a skeletal muscle-specific transcriptional regulator, activated the expression of the Cdk inhibitor p21 during differentiation of murine myocytes and in nonmyogenic cells. MyoD-mediated induction of p21 did not require the tumor suppressor protein p53 and correlated with cell cycle withdrawal. Thus, MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21.