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- W2116961946 abstract "Transforming growth factor-β (TGF-β) is a potent inhibitor of skeletal muscle differentiation, but the molecular mechanism and signaling events that lead to this inhibition are poorly characterized. Here we show that the TGF-β intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors. The Smad3-mediated repression was directed at the E-box sequence motif within muscle gene enhancers and the bHLH region of MyoD, the domain required for its association with E-protein partners such as E12 and E47. The repression could be overcome by supplying an excess of E12, and covalent tethering of E47 to MyoD rendered the E-box-dependent transcriptional activity refractory to the effects of Smad3 and TGF-β. Smad3 physically interacted with the HLH domain of MyoD, and this interaction correlated with the ability of Smad3 to interfere with MyoD/E protein heterodimerization and binding of MyoD complexes to oligomerized E-box sites. Together, these results reveal a model for how TGF-β, through Smad3-mediated transcriptional repression, inhibits myogenic differentiation." @default.
- W2116961946 created "2016-06-24" @default.
- W2116961946 creator A5056036725 @default.
- W2116961946 creator A5064800933 @default.
- W2116961946 creator A5068725149 @default.
- W2116961946 date "2001-11-15" @default.
- W2116961946 modified "2023-10-16" @default.
- W2116961946 title "TGF-β inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3" @default.
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- W2116961946 doi "https://doi.org/10.1101/gad.925901" @default.
- W2116961946 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/312830" @default.
- W2116961946 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11711431" @default.
- W2116961946 hasPublicationYear "2001" @default.
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