| Project/Area Number |
25462024
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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 |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
Saeki Hiroshi 九州大学, 医学(系)研究科(研究院), 准教授 (80325448)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA MASARU 独立行政法人国立病院機構, (九州がんセンター臨床研究センター), 統括診療部長 (30294937)
KITAO HIROYUKI 九州大学, 医学研究院, 准教授 (30368617)
OKI EIJI 九州大学, 大学病院, 講師 (70380392)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 染色体不安定性 / 集学的治療 / 消化管癌 / 染色体分配機構 / 難治性消化管癌 / PAK / 食道癌 / 遺伝子プロファイル |
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| Outline of Final Research Achievements |
Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability.
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