ArticleThe Journal of biological chemistry2012
Notch3 and Mef2c proteins are mutually antagonistic via Mkp1 protein and miR-1/206 microRNAs in differentiating myoblasts.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 102 citations in OpenAlex.
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- Necessity of Notch3 signaling in myofiber maturation in a pluripotent stem cell transplant model.Skeletal muscle · 2026Article
- Extracellular Vesicles From Young Human Myogenic Progenitor Cells Rejuvenate Aged Cells.Biochemistry research international · 2026Article
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- Regulation of myo-miR-24-3p on the Myogenesis and Fiber Type Transformation of Skeletal Muscle.Genes · 2024Article
- Regulation of muscle stem cell fate.Cell regeneration (London, England) · 2022Review
- Long non-coding RNAEpigenetics · 2022Article
- Expression of miRNA1, miRNA133, miRNA191, and miRNA24, as Good Biomarkers, in Non-Small Cell Lung Cancer Using Real-Time PCR Method.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- MicroRNA-1: Diverse role of a small player in multiple cancers.Seminars in cell & developmental biology · 2022Review
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1.Cellular and molecular life sciences : CMLS · 2022Article
- Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.Molecular medicine (Cambridge, Mass.) · 2022Article
- Non-coding RNA basis of muscle atrophy.Molecular therapy. Nucleic acids · 2021Review
- Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor.Cell death & disease · 2021Article
- MYOD1 inhibits avian adipocyte differentiation via miRNA-206/KLF4 axis.Journal of animal science and biotechnology · 2021Article
- HDAC inhibitors tune miRNAs in extracellular vesicles of dystrophic muscle-resident mesenchymal cells.EMBO reports · 2020Article
- miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNotch3 is expressed in myogenic precursors, but its function is not well known.
resultsNotch3 represses the activity of Mef2c and is in turn inhibited by the microRNAs-1 and -206.
conclusionNotch3 serves as a regulator for preventing premature myogenic differentiation. SIGNIFICANCE: Understanding how precocious differentiation is prevented is critical for designing therapy for skeletal muscle regeneration. The Notch signaling pathway is a well known regulator of skeletal muscle stem cells known as satellite cells. Loss of Notch1 signaling leads to spontaneous myogenic differentiation. Notch1, normally expressed in satellite cells, is targeted for proteasomal degradation by Numb during differentiation. A homolog of Notch1, Notch3, is also expressed in these cells but is not inhibited by Numb. We find that Notch3 is paradoxically up-regulated during the early stages of differentiation by an enhancer that requires both MyoD and activated Notch1. Notch3 itself strongly inhibits the myogenic transcription factor Mef2c, most likely by increasing the p38 phosphatase Mkp1, which inhibits the Mef2c activator p38 MAP kinase. Active Notch3 decreases differentiation. Mef2c, however, induces microRNAs miR-1 and miR-206, which directly down-regulate Notch3 and allow differentiation to proceed. Thus, the myogenic differentiation-induced microRNAs miR-1 and -206 are important for differentiation at least partly because they turn off Notch3. We suggest that the transient expression of Notch3 early in differentiation generates a temporal lag between myoblast activation by MyoD and terminal differentiation into myotubes directed by Mef2c.
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