Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation.
Smad7 is an inhibitory Smad that acts as a negative regulator of signaling by the transforming growth factor-beta (TGF-beta) superfamily proteins. Smad7 is induced by TGF-beta, stably interacts with activated TGF-beta type I receptor (TbetaR-I), and interferes with the phosphorylation of receptor-regulated Smads. Here we show that Smurf1, an E3 ... ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7. These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor.
Mesh Terms:
Activin Receptors, Type I, Amino Acid Sequence, Animals, Binding Sites, COS Cells, Cell Line, Cercopithecus aethiops, DNA-Binding Proteins, Epithelial Cells, Humans, Ligases, Mink, Protein-Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Recombinant Proteins, Sequence Alignment, Signal Transduction, Smad6 Protein, Smad7 Protein, Trans-Activators, Transfection, Transforming Growth Factor beta, Ubiquitin-Protein Ligases
Activin Receptors, Type I, Amino Acid Sequence, Animals, Binding Sites, COS Cells, Cell Line, Cercopithecus aethiops, DNA-Binding Proteins, Epithelial Cells, Humans, Ligases, Mink, Protein-Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Recombinant Proteins, Sequence Alignment, Signal Transduction, Smad6 Protein, Smad7 Protein, Trans-Activators, Transfection, Transforming Growth Factor beta, Ubiquitin-Protein Ligases
J. Biol. Chem.
Date: Apr. 20, 2001
PubMed ID: 11278251
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