Smad7 Binds to Smurf2 to Form an E3 Ubiquitin Ligase that Targets the TGFβ Receptor for Degradation
| Autor: | Richele K. Rasmussen, Gerald H. Thomsen, Shirin Bonni, Jeffrey L. Wrana, Peter A. Kavsak, Carrie G. Causing, Haitao Zhu |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Proteasome Endopeptidase Complex
Macromolecular Substances Proteolysis Recombinant Fusion Proteins Ubiquitin-Protein Ligases Immunoblotting Molecular Sequence Data Down-Regulation Plasma protein binding Transfection Models Biological Cell Line Smad7 Protein Ligases Mothers against decapentaplegic homolog 3 Interferon-gamma Downregulation and upregulation Multienzyme Complexes medicine Animals Receptor Molecular Biology Regulation of gene expression R-SMAD integumentary system medicine.diagnostic_test biology Nuclear Proteins Cell Biology Molecular biology Ubiquitin ligase Cell biology Protein Structure Tertiary DNA-Binding Proteins Cysteine Endopeptidases Protein Transport Gene Expression Regulation Mutation biology.protein Trans-Activators Lysosomes Receptors Transforming Growth Factor beta Protein Binding |
| Zdroj: | Molecular Cell. 6(6):1365-1375 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(00)00134-9 |
| Popis: | Ubiquitin-mediated proteolysis regulates the activity of diverse receptor systems. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where it causes degradation of receptors and Smad7 via proteasomal and lysosomal pathways. IFN gamma, which stimulates expression of Smad7, induces Smad7-Smurf2 complex formation and increases TGF beta receptor turnover, which is stabilized by blocking Smad7 or Smurf2 expression. Furthermore, Smad7 mutants that interfere with recruitment of Smurf2 to the receptors are compromised in their inhibitory activity. These studies thus define Smad7 as an adaptor in an E3 ubiquitin-ligase complex that targets the TGF beta receptor for degradation. |
| Databáze: | OpenAIRE |
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