Publications
Detailed Information
Therapeutic Effects of Chemical Inhibitors of AIMP2-DX2 and K-Ras Interaction on Lung Cancer : AIMP2-DX2와 K-Ras 단백질 간 결합 저해 물질의 폐암 치료 효과
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 김성훈 | - |
dc.contributor.author | 안혜원 | - |
dc.date.accessioned | 2018-05-29T04:46:07Z | - |
dc.date.available | 2020-03-02T02:36:47Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.other | 000000150808 | - |
dc.identifier.uri | https://hdl.handle.net/10371/142256 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과, 2018. 2. 김성훈. | - |
dc.description.abstract | Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2-F) is a tumor suppressor which interacts with several factors regulating cell death and growth arrest. In contrast, AIMP2-DX2, a splicing variant missing exon 2 of AIMP2-F, enhances tumorigenesis in human lung or colorectal cancer through competitive inhibitory function of AIMP2-F.
KRAS is proto-oncogene for making a protein called K-Ras protein that is involved in controlling cell division. When mutated, proto-oncogenes have the potential to cause normal cells to become cancerous. Especially, increase of mutated forms of K-Ras has been found in lung cancer patients. In previous study, AIMP2-DX2, an oncogenic variant of AIMP2, stabilizes K-Ras, and interaction of AIMP2-DX2 with K-Ras induced tumor growth. Therefore, we found therapeutic potential of interaction of AIMP2-DX2 with K-Ras in lung cancer treatment. Here we set up a cell-based Nano-luciferase binary technology (NanoBiT) to monitor the protein-protein interaction (PPI) between AIMP2-DX2 and K-Ras rapidly on 96-well scale. A total of 10000 compounds were screened for inhibitory activity on AIMP2-DX2 and K-Ras interaction, and 5 novel small molecule compounds were validated by various phenotypic experiments. Among those compounds, BC-DXI-27330 showed considerable lung cancer inhibitory efficacy in in vitro, cellular, and animal models. Through this research, we identified that the interaction between AIMP2-K-Ras is therapeutic target for human lung cancer and suggested effective small molecule compound as lung cancer medicine. | - |
dc.description.tableofcontents | I. INTRODUCTION 1
II. MATERIALS AND METHODS 4 III. RESULTS 7 1. Optimization of AIMP2-DX2:K-Ras Nano-luciferase Binary Technology (NanoBiT) assay 7 2. Compatibility of NanoBiT assay for high-throughput screening (HTS) 7 3. Pilot screening by AIMP2-DX2:K-Ras NanoBiT assay using FDA-approved library compounds 8 4. Identification of small molecule inhibitors which suppress the AIMP2-DX2:K-Ras interaction 8 5. Validation of hit compounds by dose-response NanoBiT assay and cell viability assay 9 6. Tumor suppressive efficacy of BC-DXI-27330 in K-Ras driven lung cancer model 10 IV. DISCUSSION 22 V. REFERENCES 24 VI. 국문초록 27 | - |
dc.format | application/pdf | - |
dc.format.extent | 1896746 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | AIMP2-DX2 | - |
dc.subject | K-Ras | - |
dc.subject | lung cancer | - |
dc.subject | protein-protein interaction | - |
dc.subject | NanoBiT assay | - |
dc.subject | high-throughput screening (HTS) | - |
dc.subject.ddc | 610.28 | - |
dc.title | Therapeutic Effects of Chemical Inhibitors of AIMP2-DX2 and K-Ras Interaction on Lung Cancer | - |
dc.title.alternative | AIMP2-DX2와 K-Ras 단백질 간 결합 저해 물질의 폐암 치료 효과 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Hyewon Ahn | - |
dc.description.degree | Master | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2018-02 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.