TGF-β inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3

DOI Web Site 被引用文献9件

抄録

<jats:p>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.</jats:p>

収録刊行物

  • Genes & Development

    Genes & Development 15 (22), 2950-2966, 2001-11-15

    Cold Spring Harbor Laboratory

被引用文献 (9)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ