Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activin Receptors, Type I*
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Amino Acid Sequence
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Animals
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Binding Sites
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COS Cells
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Cell Line
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Chlorocebus aethiops
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Epithelial Cells / cytology
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Epithelial Cells / physiology
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Humans
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Ligases / metabolism*
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Mink
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / physiology*
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / metabolism
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Receptors, Transforming Growth Factor beta / physiology*
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Recombinant Proteins / metabolism
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Sequence Alignment
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Signal Transduction / physiology*
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Smad6 Protein
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Smad7 Protein
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Trans-Activators / chemistry
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Trans-Activators / metabolism*
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Transfection
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Transforming Growth Factor beta / physiology*
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Ubiquitin-Protein Ligases*
Substances
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DNA-Binding Proteins
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Receptors, Transforming Growth Factor beta
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Recombinant Proteins
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SMAD6 protein, human
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SMAD7 protein, human
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Smad6 Protein
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Smad7 Protein
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Trans-Activators
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Transforming Growth Factor beta
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SMURF2 protein, human
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Ubiquitin-Protein Ligases
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Ligases