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Blockade of neddylation facilitates cancer cell migration by stabilizing c-Src : NEDD8 결합 억제에 의한 c-Src 안정화와 암세포 이동의 증가
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 전양숙 | - |
dc.contributor.author | 이건우 | - |
dc.date.accessioned | 2017-07-19T10:41:49Z | - |
dc.date.available | 2020-02-03T23:55:29Z | - |
dc.date.issued | 2017-02 | - |
dc.identifier.other | 000000140792 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133019 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 의과학과 의과학전공, 2017. 2. 전양숙. | - |
dc.description.abstract | c-Src, a well-known proto-oncogene, mediates tumor progression properties including proliferation, angiogenesis, adhesion, and migration. It is well-characterized that the stability of active c-Src is regulated by ubiquitination while other post-translational modifications of c-Src have been unknown. Here, I found that the stability of c-Src is regulated by neddylation. Furthermore, c-Cbl turned out as an E3 ligase for conjugation of NEDD8 to c-Src. Moreover, the inhibition of c-Src neddylation markedly blocked its ubiquitination. To my surprise, the blockade of neddylation by NAE inhibitor MLN4924 or si-NEDD8 promoted cancer cell migration through the elevated stability of c-Src. Such consequences by inhibition of neddylation were abolished either by the treatment of Src-family kinase inhibitor PP2 or c-Src-targeting siRNA. Also the blockade of neddylation activated PI3K/Akt/mTOR pathway in a c-Src-dependent manner. Inhibitors of PI3K/Akt/mTOR pathway also could abolish cancer cell migration induced by MLN4924. Taken together, c-Src was identified as a novel substrate for neddylation that facilitates ubiquitination-dependent degradation, which blocks the migration of cancer cells via PI3K/Akt/mTOR pathway. My study provided a new insight about the effect of c-Src modification in tumor progression. | - |
dc.description.tableofcontents | Introduction 1
Material and Methods 7 Results 13 Discussion 40 References 44 Abstract in Korean 55 | - |
dc.format | application/pdf | - |
dc.format.extent | 2853850 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | c-Src | - |
dc.subject | c-Cbl | - |
dc.subject | neddylation | - |
dc.subject | ubiquitination | - |
dc.subject | PI3K/Akt/mTOR | - |
dc.subject | cell migration | - |
dc.subject.ddc | 610 | - |
dc.title | Blockade of neddylation facilitates cancer cell migration by stabilizing c-Src | - |
dc.title.alternative | NEDD8 결합 억제에 의한 c-Src 안정화와 암세포 이동의 증가 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Gunwoo Lee | - |
dc.description.degree | Master | - |
dc.citation.pages | 56 | - |
dc.contributor.affiliation | 의과대학 의과학과 | - |
dc.date.awarded | 2017-02 | - |
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