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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

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dc.contributor.advisor전양숙-
dc.contributor.author이건우-
dc.date.accessioned2017-07-19T10:41:49Z-
dc.date.available2020-02-03T23:55:29Z-
dc.date.issued2017-02-
dc.identifier.other000000140792-
dc.identifier.urihttps://hdl.handle.net/10371/133019-
dc.description학위논문 (석사)-- 서울대학교 대학원 : 의과학과 의과학전공, 2017. 2. 전양숙.-
dc.description.abstractc-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.tableofcontentsIntroduction 1
Material and Methods 7
Results 13
Discussion 40
References 44
Abstract in Korean 55
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dc.formatapplication/pdf-
dc.format.extent2853850 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectc-Src-
dc.subjectc-Cbl-
dc.subjectneddylation-
dc.subjectubiquitination-
dc.subjectPI3K/Akt/mTOR-
dc.subjectcell migration-
dc.subject.ddc610-
dc.titleBlockade of neddylation facilitates cancer cell migration by stabilizing c-Src-
dc.title.alternativeNEDD8 결합 억제에 의한 c-Src 안정화와 암세포 이동의 증가-
dc.typeThesis-
dc.contributor.AlternativeAuthorGunwoo Lee-
dc.description.degreeMaster-
dc.citation.pages56-
dc.contributor.affiliation의과대학 의과학과-
dc.date.awarded2017-02-
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