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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Fu, Dechen Lee, Hwabin Wiper-bergeron, Nadine Lala-tabbert, Neena |
| Description | Author Affiliation: Fu D ( From the Department of Cellular and Molecular Medicine and.); Lala-Tabbert N ( Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.); Lee H ( Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.); Wiper-Bergeron N ( From the Department of Cellular and Molecular Medicine and Nadine.WiperBergeron@uottawa.ca.) |
| Abstract | Myogenesis is a tightly regulated differentiation process during which precursor cells express in a coordinated fashion the myogenic regulatory factors, while down-regulating the satellite cell marker Pax7. CCAAT/Enhancer-binding protein ß (C/EBPß) is also expressed in satellite cells and acts to maintain the undifferentiated state by stimulating Pax7 expression and by triggering a decrease in MyoD protein expression. Herein, we show that C/EBPß protein is rapidly down-regulated upon induction of myogenesis and this is not due to changes in Cebpb mRNA expression. Rather, loss of C/EBPß protein is accompanied by an increase in Mdm2 expression, an E3 ubiquitin ligase. We demonstrate that Mdm2 interacts with, ubiquitinates and targets C/EBPß for degradation by the 26 S proteasome, leading to increased MyoD expression. Knockdown of Mdm2 expression in myoblasts using a shRNA resulted in high C/EBPß levels and a blockade of myogenesis, indicating that Mdm2 is necessary for myogenic differentiation. Primary myoblasts expressing the shMdm2 construct were unable to contribute to muscle regeneration when grafted into cardiotoxin-injured muscle. The differentiation defect imposed by loss of Mdm2 could be partially rescued by loss of C/EBPß, suggesting that the regulation of C/EBPß turnover is a major role for Mdm2 in myoblasts. Taken together, we provide evidence that Mdm2 regulates entry into myogenesis by targeting C/EBPß for degradation by the 26 S proteasome. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 16 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-04-17 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CCAAT-Enhancer-Binding Protein-beta Genetics Gene Expression Regulation, Developmental Muscle Development Muscle, Skeletal Metabolism Myoblasts Proto-Oncogene Proteins C-mdm2 Animals Cell Differentiation Cell Line Mice Mice, Inbred C57BL Mice, Knockout Cytology Growth & Development MyoD Protein PAX7 Transcription Factor Primary Cell Culture Proteasome Endopeptidase Complex Proteolysis Antagonists & Inhibitors RNA, Small Interfering Signal Transduction Ubiquitination Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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