Angiogenesis regulated by an endosomal ubiquitin E3 complex
| Project/Area Number |
18K15244
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Ehime University |
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Principal Investigator |
Masashi Maekawa 愛媛大学, プロテオサイエンスセンター, 講師 (10771917)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 血管新生 / 細胞内膜輸送 / Integrin β1 / タンパク質間結合阻害剤 / ユビキチン化基質タンパク質 / 初期エンドソーム / CUL3 / エンドソーム |
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| Outline of Final Research Achievements |
The formation of new blood vessels, angiogenesis, is essential for a variety of patho-physiological events. Especially, tumor formation and metastasis require angiogenesis. To date, clinically, anti-angiogenic inhibitors exhibit good efficacy in cancer treatments. Here, we aimed to elucidate the molecular mechanisms by which an endosomal ubiquitin E3 complex, CUL3/ANKFY1, regulates angiogenesis in human endothelial cells. We identified an ANKFY1-interacting protein which is essential for both plasmalemmal localization of integrin beta 1 and angiogenesis. We also established the high through-put screen to identify inhibitors of ANKFY1/ANKFY1-interacting protein using AlphaScreen. Our results suggest the possibility of the protein interaction as a promising target for the development of new anti-angiogenic inhibitors.
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| Academic Significance and Societal Importance of the Research Achievements |
既存の血管新生阻害剤は血管内皮細胞増殖因子 (VEGF)または、VEGF受容体を標的としており、今後の有効な癌治療のためには血管新生阻害剤のレパートリーを拡充する必要がある。本研究で見出したANKFY1とANKFY1結合タンパク質との相互作用は血管新生に必須であるので、当該相互作用に対する阻害剤は新しい血管新生阻害剤のシーズになる得る。モダリティとしては、低分子化合物だけでなく、核酸アプタマーや環状ペプチドが想定される。また、ANKFY1は細胞や組織によって、異なる結合タンパク質と相互作用し、細胞、組織毎に異なる機能的膜タンパク質を輸送している可能性があり、今後の詳細な機能解明が期待される。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9.2019
Author(s)
Tanigawa K, Maekawa M, Kiyoi T, Nakayama J, Kitazawa R, Kitazawa S, Semba K, Taguchi T, Akita S, Yoshida M, Ishimaru K, Watanabe Y, Higashiyama S.
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Journal Title
J Cell Physiol.
Volume: in press
Issue: 10
Pages: 17280-17294
DOI
Related Report
Peer Reviewed / Open Access
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