Identification and functional analysis of novel regulatory molecules of polarity-regulating kinase PAR1b
Project/Area Number |
17K14986
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
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Research Institution | The University of Tokyo |
Principal Investigator |
Nishikawa Hiroko 東京大学, 大学院医学系研究科(医学部), 特任研究員 (20583131)
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Project Period (FY) |
2017-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | ピロリ菌 / 胃がん / がんタンパク質 / PAR1b / CagA / 細胞極性 |
Outline of Final Research Achievements |
Helicobacter pylori exerts its virulence by injecting the CagA oncoprotein into the host cell, and inhibiting the function of the polarity-regulating kinase, PAR1b. Thus, elucidating the physiological roles of PAR1b is crucial in understanding the mechanism underlying CagA-induced carcinogenesis. However, much of the physiological roles and the regulatory mechanisms of PAR1b remain unclear. In this study, I successfully identified a novel molecule that interacts with PAR1b. I then showed that this molecule is required for the multimerization of PAR1b in cultured cells and identified the region of PAR1b responsible for the multimerization. Moreover, I established a protocol for purifying recombinant PAR1b protein on a large scale and was successful in reconstituting the PAR1b multimer in vitro.
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Academic Significance and Societal Importance of the Research Achievements |
ピロリ菌は萎縮性胃炎、胃潰瘍、胃がん等の原因菌である。日本国内において胃がんは部位別がん死亡者数第3位であり、年間約5万人が命を落としている。ピロリ菌はがんタンパク質CagAを宿主細胞内に注入し、極性キナーゼPAR1bの機能を阻害することによりその病原性を発揮する。また、CagAはPAR1b多量体を足場として間接的に多量体化し、がん化を促進する。本研究によりPAR1b多量体化を促進する分子が同定されたことにより、今後、PAR1b多量体化の分子メカニズムおよびその生物学的意義が解明され、ピロリ菌が原因の胃粘膜病変の発症機構の解明が大いに進展すると期待される。
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Report
(3 results)
Research Products
(8 results)