Phenotypic differentiation without permanent cell-cycle arrest by skeletal myocytes with deregulated E2F-1.
Skeletal muscle terminal differentiation includes expression of muscle cell-specific proteins and concomitant cell-cycle arrest. These two processes require functional retinoblastoma protein (RB). E2F-1 is an RB-associated transcriptional factor and an effector of RB in the regulation of G1 to S-phase transition. Here, we show that proper regulation of E2F-1 is crucial for differentiation-coupled cell-cycle arrest by skeletal myocytes. On induction to differentiate, C2 myoblasts constitutively expressing E2F-1 synthesized muscle cell-specific proteins, fused into myotubes, and upregulated the cdk inhibitor p21. However, unlike control cells, differentiated myocytes expressing exogenous E2F-1 incorporated bromodeoxyuridine into nuclei, indicating S-phase entry. This S-phase entry was accompanied by expression of cyclin A. Our results support the view that RB regulates cell-cycle arrest and muscle cell differentiation through separable mechanisms.
Chen
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Department of Molecular Medicine/Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 78245-3207, USA.
Lee
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D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology*; D010641:Phenotype; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors