Abstract
We have identified the E3 ligase Traf7 as a direct MyoD1 target and show that cell cycle exit-an early event in muscle differentiation-is linked to decreased Traf7 expression. Depletion of Traf7 accelerates myogenesis, in part through downregulation of nuclear factor-κB (NF-κB) activity. We used a proteomic screen to identify NEMO, the NF-κB essential modulator, as a Traf7-interacting protein. Finally, we show that ubiquitylation of NF-κB essential modulator is regulated exclusively by Traf7 activity in myoblasts. Our results suggest a new mechanism by which MyoD1 function is coupled to NF-κB activity through Traf7, regulating the balance between cell cycle progression and differentiation during myogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle / genetics
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Cell Differentiation / genetics
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Cyclin D1 / metabolism
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Gene Expression Regulation
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I-kappa B Kinase / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Muscle Development / genetics*
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MyoD Protein / metabolism*
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Myoblasts / cytology
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Myoblasts / metabolism
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NF-kappa B / metabolism*
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Phosphorylation
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Protein Binding
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Retinoblastoma Protein / metabolism
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Transcription, Genetic*
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / deficiency
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics*
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism
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Ubiquitin / metabolism
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Ubiquitination
Substances
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Intracellular Signaling Peptides and Proteins
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MyoD Protein
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MyoD1 myogenic differentiation protein
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NEMO protein, mouse
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NF-kappa B
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Retinoblastoma Protein
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Traf7 protein, mouse
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
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Ubiquitin
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Cyclin D1
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I-kappa B Kinase