DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Joon | - |
dc.contributor.advisor | 김준 | - |
dc.contributor.author | Seo, Ji Myung | - |
dc.date.accessioned | 2022-04-21T19:33:30Z | - |
dc.date.available | 2022-04-21T19:33:30Z | - |
dc.date.issued | 2021 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=956357&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/295578 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2021.2,[ⅵ, 66 p. :] | - |
dc.description.abstract | Recent evidence suggests that hyperactive YAP is a versatile mediator of malignant processes in human cancer. Here I investigate the activation of YAP by mechanical stress in acral melanoma models. Because therapeutic targeting of the Hippo-YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulatory mechanisms in cancer, I also present a systematic functional screening and validation to identify novel therapeutic targets for YAP-driven cancers. I conducted siRNA library screening using an oncogenic YAP activation model and identified MK5 as a positive regulator of YAP activity. Depletion of MK5 causes degradation and cytoplasmic retention of YAP. MK5 physically interacts with YAP and prevents its ubiquitination and proteasomal degradation. MK5-YAP interaction counteracts CK1δ/ε–mediated YAP degradation independent of LATS1/2, the core Hippo kinases. MK5 depletion suppresses the growth of xenografted LATS1/2-null tumors as well as uveal melanoma (UVM) and malignant mesothelioma (MM) cells. Moreover, MK5 expression is associated with higher levels of YAP expression in human UVM tissues, and a MK5-related gene signature correlates with poor prognosis of UVM and MM. These results discover MK5 as a novel component of YAP protein stability regulation counteracting CK1δ/ε function. Therefore, targeting the YAP degradation pathway controlled by MK5 is a potential strategy for inhibiting YAP activity in cancer. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Hippo-YAP pathway▼amelanoma▼aMK5▼asiRNA screening▼aYAP-driven cancer | - |
dc.subject | Hippo-YAP 경로▼a흑색종▼aMK5▼asiRNA 스크리닝▼aYAP-기반 암 | - |
dc.title | Function of YAP in cancer and identification of therapeutic targets for YAP-driven tumorigenesis | - |
dc.title.alternative | 암 발달에서 YAP의 작용과 새로운 YAP 조절단백질 발굴에 관한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
dc.contributor.alternativeauthor | 서지명 | - |
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