2014 Fiscal Year Final Research Report
Novel regulators of bone-inducing activity of BMP
| Project/Area Number |
25670658
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Saitama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | BMP / Smad / 分化 / シグナル伝達 / 転写 |
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| Outline of Final Research Achievements |
Bone morphogenetic proteins (BMPs) are growth factors, which play crucial role for bone formation during embryonic development and tissue regeneration. Intracellular signaling of BMPs is induced by transmembrane serine/threonine kinase receptors to nuclei via phosphorylation reactions. Smad, MAPK and PI3K pathways have been shown to be activated by the BMP receptors. We examined the role of Smad1, Smad5, and Smad9 by creating constitutively active forms (SmadDXD). Transcriptional activity of Smad9DVD was lower than that of Smad1DXD or Smad5DXD. The linker region of Smad9 was distinguished from those of Smad1 and Smad5 and sufficient to reduce transcriptional activity. The unique structure of Smad9 linker region seemed to recruit corepressors to the target DNA. These findings suggest that BMP receptors phosphorylate signaling molecules, which regulate positively and negatively transcription of a target gene.
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| Free Research Field |
病態生理学、骨代謝学
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