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PMID: 9925645 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step.

Genes & development ·Vol. 13 ·No. 2 ·1999-01-15 ·Pages 213-24

Zhang P, Wong C, Liu D, Finegold M, Harper JW, Elledge SJ

Abstract

Cell-cycle arrest is thought to be required for differentiation of muscle cells. However, the molecules controlling cell-cycle exit and the differentiation step(s) dependent on cell-cycle arrest are poorly understood. Here we show that two Cdk inhibitors, p21(CIP1) and p57(KIP2), redundantly control differentiation of skeletal muscle and alveoli in the lungs. Mice lacking both p21 and p57 fail to form myotubes, display increased proliferation and apoptotic rates of myoblasts, and display endoreplication in residual myotubes. This point of arrest during muscle development is identical to that of mice lacking the myogenic transcription factor myogenin, indicating a role for cell-cycle exit in myogenin function. Expression of myogenin, p21, and p57 is parallel but independent, and in response to differentiation signals, these proteins are coordinately regulated to trigger both cell-cycle exit and a dependent muscle-specific program of gene expression to initiate myoblast terminal differentiation and muscle formation.

MeSH Terms
Animals Apoptosis/genetics Bone Development Cell Cycle/genetics Cell Differentiation Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p57 Cyclins/genetics,metabolism DNA/biosynthesis Female Gene Expression Regulation, Developmental Lung/abnormalities,cytology,embryology,metabolism Male Mice Mice, Transgenic Morphogenesis Muscle, Skeletal/abnormalities,cytology,embryology,metabolism Mutation Myogenin/genetics,physiology Nuclear Proteins/genetics,metabolism Phenotype RNA, Messenger/analysis
Chemicals
Cdkn1a protein, mouse Cdkn1c protein, mouse Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p57 Cyclins Myog protein, mouse Myogenin Nuclear Proteins RNA, Messenger DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhang P
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030 USA.
Wong C
Liu D
Finegold M
Harper J W
Elledge S J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.2.213
Published
1999-01-15
Pages
213-24
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316389
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.13.2.213 PMC Full Text View journal details
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