Project/Area Number |
18K07213
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50010:Tumor biology-related
|
Research Institution | Himeji Dokkyo University |
Principal Investigator |
Sakai Nobuya 姫路獨協大学, 薬学部, 講師 (30525077)
|
Co-Investigator(Kenkyū-buntansha) |
柴田 克志 姫路獨協大学, 薬学部, 教授 (70296565)
|
Project Period (FY) |
2018-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | Hippo経路 / Sav1 / BioID / RASSF1A / 癌抑制因子 / 分子シャペロン |
Outline of Final Research Achievements |
In the Hippo signaling pathway, Sav1 assumes a crucial role as an adapter protein. Previously, we have demonstrated the interaction between Sav1 and Hsp60. Within this investigation, our objective was to discern the protein complex that interacts with Sav1-Hsp60 and elucidate its implications in cell carcinogenesis and the acquisition of metastatic potential through the utilization of proximity-dependent biotin identification (BioID). HEK293 cells that expressed the BioID-Sav1 fusion protein were employed to obtain a purified fusion Sav1 protein complex. Subsequent analysis of these purified proteins via mass spectrometry identified novel signals indicating interactions with previously unidentified proteins including Hsp90. Our future endeavors involve the elucidation of the cellular physiological functions exhibited by these intricate protein complexes.
|
Academic Significance and Societal Importance of the Research Achievements |
Hippoがん抑制情報伝達経路におけるアダプター蛋白質として知られるSav1は、詳細な細胞生理学的機能について不明点が多く解明が待たれる。本研究では、近位依存性ビオチン標識(BioID)を用いて、Sav1-Hsp60と相互作用する蛋白質複合体の同定、および細胞がん化・転移能獲得への関与の解明を目的とした結果、Hsp90を含む新たなSav1相互作用蛋白質のシクナルを質量分析により検出した。今後、これらの蛋白質複合体の細胞生理学的な役割が明らかになれば、がん細胞の発生、がん細胞の転移・進展を制御する新たな分子メカニズムの解明、ひいては再生医療や新たな分子標的薬の開発に貢献できると期待される。
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