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Identification of SGK1 as a novel positive regulator of YAP and TAZ : SGK1에 의한 YAP과 TAZ의 활성조절 연구
DC Field | Value | Language |
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dc.contributor.advisor | 황덕수 | - |
dc.contributor.author | 유건 | - |
dc.date.accessioned | 2017-07-14T00:53:20Z | - |
dc.date.available | 2018-03-23 | - |
dc.date.issued | 2017-02 | - |
dc.identifier.other | 000000141325 | - |
dc.identifier.uri | https://hdl.handle.net/10371/121461 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2017. 2. 황덕수. | - |
dc.description.abstract | In recent years, an emerging role of YAP and TAZ in the increasingly sophisticated cancer biology field demands a more articulate understanding of protein networks surrounding YAP and TAZ. This also means elucidation of detailed regulatory mechanisms relevant to YAP/TAZ within the pre-established signaling pathway, is crucial to better understand the extent of YAP and TAZs activity during cancer development.
With this in mind, I worked on candidate regulatory partners of YAP and TAZ. SGK1 is an oncoprotein of the PI3-K signaling pathway with recent therapeutic implication in AKT inhibitor-resistant cancers. I confirmed that SGK1 is a downstream target of YAP with rapid responsiveness to YAP activation. Moreover, SGK1 transcription was controlled by a critical YAP-interacting transcription factor, TEAD. In addition, I found that YAP directly binds to the distal enhancer of SGK1 to promote transcription. On the other hand, I discovered that SGK1 controls canonical YAP/TAZ targets, CTGF and CYR61 via its kinase domain and PPxY motif. Furthermore, SGK1 regulates YAP and TAZ protein levels to promote CTGF and CYR61 expression. Lastly, I found that SGK1 stabilizes TAZ via GSK3β phosphorylation. Alternatively, I discovered that TAZ is regulated by its paralog, YAP, in a negative way. I found that this regulation is rather unidirectional and conserved among numerous cell lines. TAZ regulation by YAP was controlled at the translational level, but not at the transcriptional or post-translational level. Finally, I found this regulatory mechanism was independent of the Hippo signaling pathway. In conclusion, I discovered two regulatory mechanisms controlling TAZ in both positive and negative manners. | - |
dc.description.tableofcontents | CHAPTER I. Identification of SGK1 as a novel positive regulator of YAP/TAZ 1
I-1. Abstract 2 I-2. Introduction 3 I-3. Materials and Methods 7 I-4. Results 14 I-5. Discussion 53 CHAPTER II. A study on the negative regulation of TAZ by YAP 55 II-1. Abstract 56 II-2. Introduction 57 II-3. Materials and Methods 60 II-4. Results 64 II-5. Discussion 76 REFERENCES 78 ABSTRACT IN KOREAN/국문초록 89 | - |
dc.format | application/pdf | - |
dc.format.extent | 2249955 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | SGK1 | - |
dc.subject | YAP | - |
dc.subject | TAZ | - |
dc.subject | CTGF | - |
dc.subject | CYR61 | - |
dc.subject | Hippo pathway | - |
dc.subject.ddc | 570 | - |
dc.title | Identification of SGK1 as a novel positive regulator of YAP and TAZ | - |
dc.title.alternative | SGK1에 의한 YAP과 TAZ의 활성조절 연구 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Geon Yoo | - |
dc.description.degree | Doctor | - |
dc.citation.pages | xii, 90 | - |
dc.contributor.affiliation | 자연과학대학 생명과학부 | - |
dc.date.awarded | 2017-02 | - |
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