Evidence map›Paper›PMID 25720496›Full record

ArticleThe Journal of biological chemistry2015

Mdm2 promotes myogenesis through the ubiquitination and degradation of CCAAT/enhancer-binding protein β.

Dechen Fu, Neena Lala-Tabbert, Hwabin Lee, Nadine Wiper-Bergeron

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Dechen FuFrom the Department of Cellular and Molecular Medicine and.
Neena Lala-TabbertGraduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
Hwabin LeeGraduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
Nadine Wiper-BergeronFrom the Department of Cellular and Molecular Medicine and Nadine.WiperBergeron@uottawa.ca.
University of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 β (C/EBPβ) 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/EBPβ protein is rapidly down-regulated upon induction of myogenesis and this is not due to changes in Cebpb mRNA expression. Rather, loss of C/EBPβ protein is accompanied by an increase in Mdm2 expression, an E3 ubiquitin ligase. We demonstrate that Mdm2 interacts with, ubiquitinates and targets C/EBPβ 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/EBPβ 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/EBPβ, suggesting that the regulation of C/EBPβ turnover is a major role for Mdm2 in myoblasts. Taken together, we provide evidence that Mdm2 regulates entry into myogenesis by targeting C/EBPβ for degradation by the 26 S proteasome.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsCCAAT-Enhancer-Binding Protein-betaCell DifferentiationCell LineHumansMiceMice, Inbred C57BLMice, KnockoutMuscle DevelopmentMuscle, SkeletalMyoblastsMyoD ProteinPAX7 Transcription FactorPrimary Cell CultureProteasome Endopeptidase ComplexATP dependent 26S proteaseCCAAT-Enhancer-Binding Protein-betaCebpb protein, mouseMdm2 protein, mouseMyoD1 myogenic differentiation proteinMyoD ProteinPax7 protein, mousePAX7 Transcription FactorProteasome Endopeptidase ComplexProto-Oncogene Proteins c-mdm2RNA, Small InterferingCCAAT-enhancer-binding protein (C/EBP)mouse double minute 2 homolog (MDM2)muscle regenerationmyogenesisubiquitylation (ubiquitination)

Identifiers

PMID25720496
PMCPMC4400335
OpenAlexW2073794835

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.