| | |  | | | | Record from Web of Science® | | | | | | |
| Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation |
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| Author(s): Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu HT, Thomsen GH, Wrana JL |
| Source: MOLECULAR CELL Volume: 6 Issue: 6 Pages: 1365-1375 Published: DEC 2000 |
| Times Cited: 403 References: 34 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Wrana, JL (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5 Canada |
Addresses:
1. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5 Canada
2. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8 Canada
3. SUNY Stony Brook, Dept Biochem & Cell Biol, Ctr Dev Genet, Stony Brook, NY 11794 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 389LN |
| ISSN: 1097-2765 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |