2002 Fiscal Year Final Research Report Summary
Control of TGFβ signaling by degradation of Smads, TGFβ signal transducers
| Project/Area Number |
13672294
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
HAYASHI Hidetoshi Grad. Sch. Pharm. Sci., Assoc. Prof., 薬学研究科, 助教授 (80198853)
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| Co-Investigator(Kenkyū-buntansha) |
ONOZAKI Kikuo Grad. Sch. Pharm. Sci., Prof., 薬学研究科, 教授 (20101313)
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| Project Period (FY) |
2001 – 2002
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| Keywords | TGFβ / Smad / Smurf / E3 ligase / proteasome / ubiquitination / Smurf / acetylation |
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| Research Abstract |
Smad proteins are crucial molecules for the intracellular signaling of transforming growth factor-β (TGF-β). Upon receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate transcription of a select set of target genes. Here we investigated the turnover of Smad3, positively regulating Smad for TGF-β signaling. In the steady state, proteasome inhibition leads to the stabilization of Smad3 protein. Smad proteins are multi-ubiquitinated and degraded independently of its phosophorylation induced by the TGF-β receptors. Moreover, the degradation of Smad3 was enhanced by the treatment with TGF-β, and phosphorylated Smad3 was accumulated by proteasome inhibition. In addition, ubiquitination of phosphorylated Smad3 but not SmadS (3SA), a receptor-mediated phosphorylation incompetent mutant, was observed in the nucleus after treatment with TGF-β. These studies suggest that at steady state Smad3 is constitutively degraded through ubiquitin proteasome pathway in the cytoplasm and that in response to TGF-β it is phosphorylated and translocates into nuclei, where it is degraded through ubiquitin proteasome pathway.
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