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An Oncogenic Variant of AIMP2 Enhances K-Ras Stability via Heat Shock Protein Complex : 발암성 변이체 AIMP2가 Heat Shock Protein Complex을 매개체로 하여 K-Ras를 안정화시켜 대장암을 유발시키는 과정에 대한 규명
DC Field | Value | Language |
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dc.contributor.advisor | 김성훈 | - |
dc.contributor.author | 노윤아 | - |
dc.date.accessioned | 2018-05-29T04:45:11Z | - |
dc.date.available | 2021-04-13T02:09:57Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.other | 000000151091 | - |
dc.identifier.uri | https://hdl.handle.net/10371/142248 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과, 2018. 2. 김성훈. | - |
dc.description.abstract | K-Ras is one of Ras small GTPase family and it facilitates diverse cell signaling. Many researches have shown that mutated K-Ras induces colorectal cancer. For last few decades, there have been intensive efforts to understand oncological implications of mutated K-Ras and to control its stability. However, these efforts fail to provide the amplification mechanisms of pathological level of K-Ras and also they could not provide clinically useful outcome to control the activity or expression level of K-Ras.
Here, I report the veiled mechanism of the pathological implication and stabilization of K-Ras. I propose AIMP2-DX2, as known as an exon2-deleted splicing variant of AIMP2 (aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2), is the key factor regulating K-Ras. The GST domain of AIMP2-DX2 binds to the hypervariable region of K-Ras specifically. After AIMP2-DX2 and K-Ras interact each other, AIMP2-DX2 recruits the heat shock proteins, HSP70 and HSP90, to facilitated proper folding of K-Ras. This process enhances the stability and oncogenicity of K-Ras, which results the aggressive tumor progression. In the presence of both proteins, AIMP2-DX2 and K-Ras, the tumor progression is much more noticeable in vitro, in vivo conditions and tissue samples of colorectal cancer patients. Therefore, I suggest that regulating the level of AIMP2-DX2 could be the one of the key factors to control the stability and oncogenicity of K-Ras. Through this study, I believe that AIMP2-DX2-mediated novel mechanism of K-Ras is a strong therapeutic implication of colorectal cancer. | - |
dc.description.tableofcontents | I. INTRODUCTION 1
II. MATERIALS AND METHODS 4 2.1 Anchorage-independent colony formation assay 4 2.2 Cell Culture and Materials 4 2.3 Generation of inducible AIMP2-DX2 knock-in mouse and embryonic fibroblast cells 5 2.4 Immunohistochemistry 6 2.5 Interactive Analysis 7 2.6 In vivo analysis 9 2.7 MTT 10 2.8 NMR Analysis 10 2.9 Patient analysis 11 2.10 Quantitative co-immunoprecipitation 11 2.11 Quantitative in vitro pull down assay 12 III. RESULTS 13 3.1 AIMP2-DX2 specifically stabilizes K-Ras via binding 13 3.2 Threonine 85 and Lysine 90 of AIMP2-DX2 are critical for binding with K-Ras 14 3.3 Interactome analysis of K-Ras 15 3.4 AIMP2-DX2 recruits the chaperone complex, HSP70 and HSP90, to K-Ras for further folding 16 3.5 Determination of the domains of K-Ras, HSP70 and HSP90 that involved in the binding interaction 16 3.6 AIMP2-DX2 enhances the oncogenicity of K-Ras 17 3.7 Positive correlation of AIMP2-DX2 and K-Ras in colon cancer 18 IV. DISCUSSION 35 V. REFERENCES 38 VI. 국문초록 42 | - |
dc.format | application/pdf | - |
dc.format.extent | 1528558 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | AIMP2-DX2 | - |
dc.subject | Colorectal Cancer | - |
dc.subject | Hsp70 | - |
dc.subject | Hsp90 | - |
dc.subject | Heat Shock Protein Complex | - |
dc.subject | K-Ras | - |
dc.subject | Oncogenicity | - |
dc.subject | Pathological implication | - |
dc.subject | Therapeutic implication | - |
dc.subject.ddc | 610.28 | - |
dc.title | An Oncogenic Variant of AIMP2 Enhances K-Ras Stability via Heat Shock Protein Complex | - |
dc.title.alternative | 발암성 변이체 AIMP2가 Heat Shock Protein Complex을 매개체로 하여 K-Ras를 안정화시켜 대장암을 유발시키는 과정에 대한 규명 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Youn-Ah Roh | - |
dc.description.degree | Master | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2018-02 | - |
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