| Project/Area Number |
17K19581
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Miyazono Kenichi 東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (90554486)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | がん / TGF-β / ペプチドアプタマー / ペプチド工学 / シグナル伝達 / 制御 / 蛋白質 |
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| Outline of Final Research Achievements |
SMAD2/3 are hub proteins that regulate TGF-beta signaling in cell. In this study, we have designed and developed peptide aptamers that bind strongly to SMAD2/3. The peptide aptamers, which are produced by the tandem linkage of SMAD2/3 cofactors, are expected to regulate the function of TGF-beta signaling in cell by the competition with SMAD2/3 cofactors. Among SMAD2/3 cofactors, SMAD2/3 binding domains of SARA, FOXH1 and SKI were fused in tandem, and their SMAD2/3 binding abilities were evaluated by surface plasmon resonance assay. One of the peptide aptamers binds strongly to SMAD2/3 with dissociation constants of nanomolar order. In addition, we have determined the crystal structures of SMAD2/3-cofactor complexes and presented the results as papers.
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| Academic Significance and Societal Importance of the Research Achievements |
TGF-βシグナル伝達の異常は、がんの悪性化や線維症の発症など重篤な疾病と関連している。これらの疾病の治療において、TGF-βシグナル伝達系は有望な創薬ターゲットと考えられているが、その制御はシグナルの上流部分を対象とすることがほとんどであった。本研究では、シグナル下流で生じる生命現象（タンパク質分子間相互作用）に着目し、その制御を目指した。本研究の成果に基づき、シグナル伝達系下流における制御が可能となれば、より副作用の少ない形でTGF-βシグナルが制御できるようになると期待され、がんや線維症の新たな治療法の開発へとつながる可能性がある。
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