| Project/Area Number |
25440096
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Shigeru Makino 国立研究開発法人理化学研究所, バイオリソースセンター, 開発研究員 (30462732)
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| Co-Investigator(Renkei-kenkyūsha) |
GONDO Yoichi 国立研究開発法人理化学研究所, バイオリソースセンター, チームリーダー (40225678)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ヘッジホグシグナル伝達 / GLI転写因子 / SUFU / 突然変異マウス / タンパク質の可視化 / ゲノム編集 / CRISPR-Cas9 / 翻訳再開 / GLI3転写因子 / Sufu / Gli転写因子 / マウス / ENU突然変異 / 神経管形成 / 四肢形態形成 / イメージング |
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| Outline of Final Research Achievements |
Hedgehog signaling (Hh) has important roles in fetal development and diseases. SUFU is a cytoplasmic component of Hh signaling and is known to regulate the primary transcription factors, GLI1 and GLI2 activators and GLI3 repressor. However, little is known about the protein function of SUFU. In this project, we analyzed originally-developed mutant mice carrying point mutations in the Sufu gene, and found that SUFU played a central role in demarcating its regulatory actions of GLI1/2 activator and GLI3 repressor.
In addition, we found that translation reinitiation unexpectedly occurred in Gli3 knockout cell lines created by a gnome-editing technology, CRISPR-Cas9 system. We propose that translation reinitiation is recognized as a critical regulatory mechanism for gene expression as a new paradigm of the central dogma and possible future application to the gene therapy.
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