Analysis of novel CUL3 complex-mediated angiogenesis regulatory pathway
| Project/Area Number |
18K07234
|
|---|
| 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 | Ehime University |
|---|
Principal Investigator |
Sakaue Tomohisa 愛媛大学, 医学系研究科, 講師(特定教員) (20709266)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 血管新生 / ユビキチンリガーゼ / CUL3 / がん / 心疾患 / 網膜 / 基質 / AlphaScreen / KCTD / タンパク質分解 / 血管内皮細胞 / ユビキチン / E3ユビキチンリガーゼ / アクチン骨格 / 細胞骨格 / アクチン |
|---|
| Outline of Final Research Achievements |
Clarification of the molecular mechanisms underlying angiogenesis can lead to a better understanding of various pathological conditions such as cancer and ischemic diseases. Recently, we found that CUL3-based E3 ubiquitin ligase expressed in vascular endothelial cells plays an important role in the progression of angiogenesis. However, intracellular mechanisms of CUL3-induced angiogenesis remained unclear. In the present study, we analyzed the phenotypes that are expressed by functional inhibition of the CUL3-based E3 ubiquitin ligase complex in vascular endothelial cells in vivo and in vitro. Our findings suggest that the CUL3-based E3 ubiquitin ligase is involved in RhoB-mediated actin depolymerization to accelerate angiogenesis. Functional inhibition of the CUL3-based E3 ubiquitin ligase may be a good target for the development of therapeutic drugs.
|
| Academic Significance and Societal Importance of the Research Achievements |
がん進展に対してはがん細胞が血管新生を呼び込み、酸素や栄養を獲得することが腫瘍増大や転移を招くことがよく知られている。また虚血性疾患においては血管新生の誘導を介した組織への酸素や栄養の供給が不可欠である。このような血管新生の促進や阻害を人為的に可能とする疾患治療開発の標的としてCUL3型E3ユビキチンリガーゼを見出し、その血管新生の分子メカニズムの一端を明らかにできたことは非常に有意義であり、今後の創薬へとつながる可能性がある。
|
Report
(5 results)
Research Products
(26 results)
