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2020 Fiscal Year Final Research Report

Structure-function analysis for the induction of pathogenic signaling by H. pylori CagA oncoprotein

Research Project

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Project/Area Number 18K07105
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hayashi Takeru  東京大学, 大学院医学系研究科(医学部), 助教 (10722209)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywords胃がん / ピロリ菌 / CagA / 新規創薬
Outline of Final Research Achievements

Helicobacter pylori CagA oncoprotein is closely associated with gastric carcinogenesis. In this study, I succeeded in reconstitution of the complex formation of CagA with multiple human proteins. CagA-SHP2 complex formation was promoted by CagA-PAR1b interaction and, in contrast, suppressed by CagA-Csk interaction, which required homo-dimerization of Csk. Thus, a series of analyses revealed that the CagA interacts with multiple proteins in a more complicated manner than expected. Furthermore, I found small compounds with novel chemical structures that selectively inhibit SHP2 oncoprotein, which is aberrantly activated by CagA.

Free Research Field

胃がん発症の分子機構

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌CagAは胃がんに深く関わり、CagAによるヒトタンパク質の脱制御がその病原活性の本態と考えられる。本研究の解析により、CagAが細胞内のPAR1b、SHP2ならびにCskと形成するシグナル撹乱複合体の生化学的性質が新たに明らかになった。また、がんタンパク質として明確な位置づけにあるSHP2は、依然としてその機能に不明な点が多いものの近年創薬の標的としても大きな注目を浴びている。本研究ではSHP2の新たな機能を明らかにするとともに、新規創薬への展開が期待できる結果を得た。

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Published: 2022-01-27  

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