Mdm2 Promotes Myogenesis through the Ubiquitination and Degradation of CCAAT/Enhancer-binding Protein β

Fu, Dianzheng; Lala-Tabbert, Neena; Lee, Hwabin; Wiper‐Bergeron, Nadine

doi:10.1074/jbc.m115.638577

Cited by 40 publications

(56 citation statements)

References 41 publications

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“…The transcription factor CCAAT/enhancer-binding protein b (C/EBPb), is an important regulator of mesenchymal stem cell fate and is upregulated in muscle wasting, such as sarcopenia [15]. Our work has shown that in healthy muscle, C/EBPb expression is localized to Pax7 + satellite cells and its expression is downregulated during myogenesis in parallel with Pax7 [16,17]. Forced expression of C/EBPb in myoblasts stimulates Pax7 expression, reduces MyoD protein expression, and inhibits myogenesis.…”

Section: Introductionmentioning

confidence: 90%

“…Our work has shown that in healthy muscle, C/EBPb expression is localized to Pax7 + satellite cells and its expression is downregulated during myogenesis in parallel with Pax7 [16,17]. Forced expression of C/EBPb in myoblasts stimulates Pax7 expression, reduces MyoD protein expression, and inhibits myogenesis.…”

Section: Introductionmentioning

confidence: 95%

“…1A). Given that high C/EBPb levels correlate with reductions in MyoD protein expression [16,17], the stable MyoD expression in the presence of IBMX was surprising and suggested that IBMX can maintain MyoD levels independent of its effects on C/EBPb expression. Indeed, treatment with forskolin (an activator of adenylyl cyclase) upregulates MyoD expression in isolated primary myoblasts [34].…”

Section: Ibmx Upregulates C/ebpb Expression and Reversibly Inhibits Mmentioning

confidence: 99%

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Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle

Lala-Tabbert

Wiper‐Bergeron

2016

Stem Cells Translational Medicine

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This study demonstrates that treatment with isobutylmethylxanthine is an efficient method of expanding muscle progenitor cells, while preserving regenerative potential, before transplantation. Phosphodiesterase inhibitor treatment improves myoblast culture conditions in such a way as to reinvigorate myoblast transplantation as a viable therapeutic approach to halt muscle wasting in Duchenne muscular dystrophy.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 95%

Section: Ibmx Upregulates C/ebpb Expression and Reversibly Inhibits Mmentioning

confidence: 99%

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Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle

Lala-Tabbert

Wiper‐Bergeron

2016

Stem Cells Translational Medicine

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“…In healthy muscle, satellite cells express C/EBPb which inhibits myogenic differentiation 9,10 . Upon induction of differentiation, C/EBPβ expression dramatically decreases, allowing differentiation to proceed [9][10][11] . We observed that the anti-C/EBPb antibody (E299, ab32358) also detects myosin light chain 4 (MYL4) in differentiating myoblasts and in other cell lines.…”

Section: Introductionmentioning

confidence: 99%

Contaminating reactivity of a monoclonal CCAAT/Enhancer Binding Protein β antibody in differentiating myoblasts

AlSudais

Wiper‐Bergeron

2019

Preprint

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Objective CCAAT/Enhancer Binding proteins (C/EBPs) are transcription factors involved in the regulation of a variety of cellular processes. We used the Abcam Recombinant Anti-C/EBP beta antibody (E299) to detect C/EBPβ expression during myogenesis. Though the antibody is monoclonal, and the immunogen used is highly specific to C/EBPβ, we identified an intense band at 23 kDa on western blot that did not correspond to any of the known isoforms of C/EBPβ, or family members predicted to cross-react. Absent in myoblast cells overexpressing C/EBPβ, the band was present when C/EBPβ was knocked down, confirming specificity for a protein other than C/EBPβ. The objective of this work was to identify the contaminating reactivity. Results We performed immunoprecipitation followed by mass spectrometry to identified myosin light chain 4 (MYL4) as the unknown band, suggesting that the Abcam monoclonal antibody directed against C/EBPβ is not pure, but contains a contaminating antibody against MYL4. Caution should be used when working in cells lines that express MYL4 to not confound the detection of MYL4 with that of the C/EBPβ LIP isoform.

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“…In skeletal muscle, C/EBPβ expression is localized to Pax7 + SCs of healthy muscle and is rapidly downregulated upon induction to differentiate [19, 20]. In vivo, loss of C/EBPβ expression in SCs resulted in larger muscle fiber cross-sectional area, fewer fibers, and improved repair after a single acute muscle injury [19, 20]. When overexpressed in the murine myoblast cell line C2C12 or in primary myoblasts, C/EBPβ reduced MyoD and other myogenic protein levels during differentiation, in addition to reducing myoblast fusion.…”

Section: Introductionmentioning

confidence: 99%

CCAAT/enhancer binding protein β is required for satellite cell self-renewal

et al. 2016

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BackgroundPostnatal growth and repair of skeletal muscle relies upon a population of quiescent muscle precursor cells, called satellite cells that can be activated to proliferate and differentiate into new myofibers, as well as self-renew to replenish the satellite cell population. The balance between differentiation and self-renewal is critical to maintain muscle tissue homeostasis, and alterations in this equilibrium can lead to chronic muscle degeneration. The transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is expressed in Pax7+ satellite cells of healthy muscle and is downregulated during myoblast differentiation. Persistent expression of C/EBPβ upregulates Pax7, inhibits MyoD, and blocks myogenic differentiation.MethodsUsing genetic tools to conditionally abrogate C/EBPβ expression in Pax7+ cells, we examined the role of C/EBPβ in self-renewal of satellite cells during muscle regeneration.ResultsWe find that loss of C/EBPβ leads to precocious differentiation at the expense of self-renewal in primary myoblast and myofiber cultures. After a single muscle injury, C/EBPβ-deficient satellite cells fail to self-renew resulting in a reduction of satellite cells available for future rounds of regeneration. After a second round of injury, muscle regeneration is impaired in C/EBPβ conditional knockout mice compared to wild-type control mice. We find that C/EBPβ can regulate Notch2 expression and that restoration of Notch activity in myoblasts lacking C/EBPβ prevents precocious differentiation.ConclusionsThese findings demonstrate that C/EBPβ is a novel regulator of satellite cell self-renewal during muscle regeneration acting at least in part through Notch2.

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Mdm2 Promotes Myogenesis through the Ubiquitination and Degradation of CCAAT/Enhancer-binding Protein β

Cited by 40 publications

References 41 publications

Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle

Induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine Improves Myoblast Engraftment Into Dystrophic Muscle

Contaminating reactivity of a monoclonal CCAAT/Enhancer Binding Protein β antibody in differentiating myoblasts

CCAAT/enhancer binding protein β is required for satellite cell self-renewal

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