Analysis of a novel target of Greatwall kinase identified by chemical genetics method
| Project/Area Number |
15K07041
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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 | Tokyo Institute of Technology |
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Principal Investigator |
Okumura Eiichi 東京工業大学, 生命理工学院, 助教 (00323808)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Greatwall / Gwl / M期 / 染色体 / ゲノム / タンパク質 / 生理活性 / 生体分子 / 蛋白質 |
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| Outline of Final Research Achievements |
Cell division at M-phase is controlled by several mitotic kinases. Greatwall (Gwl) is an essential mitotic kinase. Gwl down regulates PP2A-B55 phosphatase through Arpp19/Ensa phosphorylation at the mitotic entry. Gwl also controls the mitotic progression but its substrate(s) is/are unknown. This research aimed identification of the substrate(s). 15 candidates are found by chemical genetics method in our previous work. One of the candidates, that would have affinity to chromosomes, is focused to analyze. Questions are whether it is the direct target of Gwl and what is the role in the mitotic progression. A fragment peptide of the candidate was phosphorylated by active Gwl kinase in vitro. Antibody against the fragment detected a band at predicted size of the candidate. The candidate was phosophorylated at M-phase depending not only on Gwl but also on Cdk1. Several results suggested that the candidate might control chromosome segregation.
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| Academic Significance and Societal Importance of the Research Achievements |
Gwlによる細胞周期のM期開始制御は解析が進んでいたが、GwlによるM期進行制御は不明であった。本研究の学術的意義は、M期進行を制御する基質候補を初めて見いだした点である。細胞内での役割の詳細はさらなる解析が必要であるが、染色体と相互作用する因子を直接リン酸化し、これが染色体分離制御に関わることが示唆された。Gwlのヒト相同遺伝子はMASTLと呼ばれ、この遺伝子がないと致死であり、点変異により血小板が減少する臨床的知見がある。また染色体分離異常は、染色体数の異常やがん化の原因となる。社会的意義として、こうした異常を引き起こすメカニズムの基礎的な知見が得られたと言える。
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Report
(5 results)
Research Products
(4 results)
