ArticleMolecular and cellular biology2013
Identification of Map4k4 as a novel suppressor of skeletal muscle differentiation.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Lrrc75b is a novel negative regulator of C2C12 myogenic differentiation.International journal of molecular medicine · 2016Pooled it
- Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics.Molecular endocrinology (Baltimore, Md.) · 2014Trial
- Ageing Signatures and Disturbed Muscle Regeneration in Muscle Proteome of Inclusion Body Myositis.Journal of cachexia, sarcopenia and muscle · 2025Article
- Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB.NPJ Regenerative medicine · 2024Article
- MAP4K4 expression in cardiomyocytes: multiple isoforms, multiple phosphorylations and interactions with striatins.The Biochemical journal · 2021Article
- MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model.Neural regeneration research · 2021Article
- Neratinib degrades MST4 via autophagy that reduces membrane stiffness and is essential for the inactivation of PI3K, ERK1/2, and YAP/TAZ signaling.Journal of cellular physiology · 2020Article
- AlteredDisease models & mechanisms · 2020Article
- STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells.eLife · 2020Article
- Human serum and platelet lysate are appropriate xeno-free alternatives for clinical-grade production of human MuStem cell batches.Stem cell research & therapy · 2018Article
- MiR-23-TrxR1 as a novel molecular axis in skeletal muscle differentiation.Scientific reports · 2017Article
- Differentiation capacities of skeletal muscle satellite cells in Lantang and Landrace piglets.Oncotarget · 2017Article
- SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Dexamethasone Treatment at the Myoblast Stage Enhanced C2C12 Myocyte Differentiation.International journal of medical sciences · 2017Article
- Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets.Journal of computer-aided molecular design · 2016Article
- Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases.Trends in endocrinology and metabolism: TEM · 2016Review
- MAP4K4: an emerging therapeutic target in cancer.Cell & bioscience · 2016Review
- Article
- Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis.Nature communications · 2015Article
- Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover.Physiological genomics · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Myoblast differentiation into mature myotubes is a critical step in the development and repair of human skeletal muscle. Here we show that small interfering RNA (siRNA)-based silencing of the Ste20-like mitogen-activated protein 4 kinase 4 (Map4k4) in C2C12 myoblasts markedly enhances expression of myogenic differentiation genes, myoblast fusion, and myotube diameter. In contrast, adenovirus-mediated expression of native Map4k4 in C2C12 cells attenuates each of these processes, indicating that Map4k4 is a negative regulator of myogenic differentiation and hypertrophy. Expression of a Map4k4 kinase-inactive mutant enhances myotube formation, suggesting that the kinase activity of Map4k4 is essential for its inhibition of muscle differentiation. Map4k4 regulation of myogenesis is unlikely to be mediated by classic mitogen-activated protein kinase (MAPK) signaling pathways, because no significant difference in phosphorylation of extracellular signal-regulated kinase (ERK), p38, or c-Jun N-terminal kinase (JNK) is observed in Map4k4-silenced cells. Furthermore, silencing of these other MAPKs does not result in a hypertrophic myotube phenotype like that seen with Map4k4 depletion. Uniquely, Map4k4 silencing upregulates the expression of the myogenic regulatory factor Myf5, whose depletion inhibits myogenesis. Furthermore, Myf5 is required for enhancement of myotube formation in Map4k4-silenced cells, while Myf5 overexpression rescues Map4k4-mediated inhibition of myogenic differentiation. These results demonstrate that Map4k4 is a novel suppressor of skeletal muscle differentiation, acting through a Myf5-dependent mechanism.
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