Retracted: MyoD-dependent regulation of NF-κB activity couples cell-cycle withdrawal to myogenic differentiation
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Dossier post-publication
- Nature
- Retraction
- Motif
- Falsification/Fabrication of Image;
- Date
- 7/18/2013 0:00
- Signalé par OpenAlex ?
- Oui
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Résumé
BACKGROUND: Mice lacking MyoD exhibit delayed skeletal muscle regeneration and markedly enhanced numbers of satellite cells. Myoblasts isolated from MyoD-/- myoblasts proliferate more rapidly than wild type myoblasts, display a dramatic delay in differentiation, and continue to incorporate BrdU after serum withdrawal. METHODS: Primary myoblasts isolated from wild type and MyoD-/- mutant mice were examined by microarray analysis and further characterized by cell and molecular experiments in cell culture. RESULTS: We found that NF-κB, a key regulator of cell-cycle withdrawal and differentiation, aberrantly maintains nuclear localization and transcriptional activity in MyoD-/- myoblasts. As a result, expression of cyclin D is maintained during serum withdrawal, inhibiting expression of muscle-specific genes and progression through the differentiation program. Sustained nuclear localization of cyclin E, and a concomitant increase in cdk2 activity maintains S-phase entry in MyoD-/- myoblasts even in the absence of mitogens. Importantly, this deficit was rescued by forced expression of IκBαSR, a non-degradable mutant of IκBα, indicating that inhibition of NF-κB is sufficient to induce terminal myogenic differentiation in the absence of MyoD. CONCLUSION: MyoD-induced cytoplasmic relocalization of NF-κB is an essential step in linking cell-cycle withdrawal to the terminal differentiation of skeletal myoblasts. These results provide important insight into the unique functions of MyoD in regulating the switch from progenitor proliferation to terminal differentiation.
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La notice
- Revue
- Skeletal Muscle
- Thématique
- Muscle Physiology and Disorders
- Domaine
- Biochemistry, Genetics and Molecular Biology
- Établissements canadiens
- McMaster UniversityOttawa Hospital
- Organismes subventionnaires
- Canadian Institutes of Health ResearchNational Institutes of HealthMuscular Dystrophy AssociationHoward Hughes Medical Institute
- Mots-clés
- MyoDCell biologyNeuroscienceBiologyMyogenesisMyocyte
- Résumé présent dans OpenAlex
- oui