2020 Fiscal Year Final Research Report
Analysis of cancer specific signaling cascade by in vivo protein photo-cross-linking approach
Project/Area Number |
19K22496
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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Research Institution | Osaka University |
Principal Investigator |
DOI Takefumi 大阪大学, 薬学研究科, 教授 (00211409)
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Co-Investigator(Kenkyū-buntansha) |
樋野 展正 大阪大学, 薬学研究科, 助教 (90469916)
山口 卓男 大阪大学, 薬学研究科, 講師 (80596601)
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Project Period (FY) |
2019-06-28 – 2021-03-31
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Keywords | がんゲノム / 融合型キナーゼ / タンパク質間相互作用 / クロスリンク / 人工アミノ酸 |
Outline of Final Research Achievements |
Most fusion protein kinases, which are generated by cancer genome instability, show abnormal subcellular localization and contribute to malignant transformation of cancer by activating unusual signaling cascades. In this study, we employed unique in vivo protein photo-cross-linking approach to identify proteins that are direct substrates of fused protein kinases and reveal the abnormal signaling pathway. We introduced a photo-cross-linkable amino acid into the substrate recognition region of EGFR kinase and analyzed whether it could capture the substrate by cross-linking, suggesting binding to some endogenous proteins. In parallel, we developed a method to specifically label the proteins captured by the cross-linking to improve the efficiency of substrate identification.
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Free Research Field |
ケミカルバイオロジー、細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
融合型キナーゼにより惹起される異常なシグナルカスケードの解明は、過去20年以上に渡り世界的に取り組まれてきた課題である。本研究では、特定のキナーゼの基質を細胞内における両者の直接的な相互作用をもとに同定するという新規アプローチを提案し、基質の同定効率向上に資する技術開発も行なった。これらを元に、融合型キナーゼの下流カスケードを特異的に明らかにできれば、がん征圧に向けた重要な布石になると考えられる。
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