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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳瑞華(Ruey-Hwa Chen) | |
dc.contributor.author | Liang-Yu Pang | en |
dc.contributor.author | 龎亮瑜 | zh_TW |
dc.date.accessioned | 2021-06-16T08:19:34Z | - |
dc.date.available | 2019-02-25 | |
dc.date.copyright | 2014-02-25 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-02-07 | |
dc.identifier.citation | References
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58551 | - |
dc.description.abstract | 細胞透過細胞自噬維持細胞恆定,並藉由回收細胞質中物質幫助細胞度過逆境。ULK1蛋白作為細胞自噬過程中最重要的蛋白激酶調控了細胞自噬從早期到晚期的各個步驟,然而目前尚未完全清楚ULK1如何受到調控。在此篇研究中,我們發掘一個透過Cul3-KLHL20複合體E3泛素連接酶調控之ULK1蛋白酶體降解機制。Cul3-KLHL20複合體能夠促進ULK1泛素化及降解並於細胞養分充足狀態下調控細胞自噬的基礎活性。更重要的是我們發現細胞自噬的活化能夠促進KLHL20所調控之ULK1降解。在細胞養分不足時,KLHL20和ULK1的結合會逐漸增加而ULK1蛋白質則因降解而逐漸減少。此外,內質網壓力、粒腺體損壞等逆境所刺激之細胞自噬也會活化相同的調控機制。KLHL20所調控的ULK1降解控制了細胞自噬的活性以及活化時間進而避免細胞自噬活化過久及活性過強所造成的損害。在這篇研究中,我們發現了一個從未被報導過的ULK1的調控機轉,此一機轉可能對於維持細胞恆定相當重要。 | zh_TW |
dc.description.abstract | Autophagy, a cellular self-eating mechanism, is important for maintaining homeostasis and recycling cytosolic materials in response to various stresses such as starvation. ULK1 is the most critical protein kinase whose function in autophagy spans throughout early to late stage. However, the regulatory mechanism of ULK1 remains largely elusive. In this thesis, we discovered a novel ubiquitin-proteasomal regulation of ULK1 mediated by Cul3-KLHL20 complex, an E3 ubiquitin ligase. At nutrient rich conditions, we demonstrated that Cul3-KLHL20 promotes ULK1 ubiquitination and degradation, and thus controls the activity of basal autophagy. More importantly, we showed that KLHL20-mediated ULK1 degradation is stimulated by the activation of autophagy. During starvation, KLHL20 and ULK1 interaction is gradually increased while the amount of ULK1 is gradually decreased. The similar mode of ULK1 regulation occurs during autophagy induced by ER stress, mitochondria damage and other stress conditions. We further showed that this KLHL20-dependent ULK1 regulation controls the amplitude and duration of autophagy to prevent prolonged or overly activated autophagy. This study identifies a novel regulatory mechanism for ULK1 and suggests a key role of this regulation in maintaining cell homeostasis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T08:19:34Z (GMT). No. of bitstreams: 1 ntu-103-R00448016-1.pdf: 14424608 bytes, checksum: 4f980a8df9c4e28f13ed4e182b7639df (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員審定書
致謝 i 摘要 ii Abstract iii Introduction 1 1. Autophagy 1 1.1 ULK1 in the Regulation of Autophagy 2 1.2 Regulation of ULK1 4 2. Ubiquitin-Proteasome System 7 2.1 KLHL20 8 Material and Methods 10 Cell culture 10 Plasmids 10 Transient transfection and lentivirus infection 11 Antibodies and reagents 11 Immunoprecipitation 11 Western blot 12 Autophagy assay 12 Results 13 KLHL20 interacts with ULK1 13 Cul3-KLHL20 E3 ligase promotes ULK1 ubiquitination and degradation 14 KLHL20 is a general regulator of autophagy 15 KLHL20 mediates autophagy-induced ULK1 downregulation 16 KLHL20 regulates the duration of autophagy 18 Starvation promotes the interaction between KLHL20 and ULK1 19 Discussion 20 References 26 Figures 32 Appendixes 44 | |
dc.language.iso | en | |
dc.title | 探討細胞自噬所調控之ULK1蛋白泛素化修飾及降解 | zh_TW |
dc.title | Autophagy-reugulated ubiquitination and proteasomal degradation of ULK1 | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳光超(Guang-Chao Chen),吳君泰(June-Tai Wu) | |
dc.subject.keyword | 細胞自噬,泛素,蛋白?體,ULK1,cullin3,KLHL20, | zh_TW |
dc.subject.keyword | autophagy,ubiquitin,proteasome,ULK1,cullin3,KLHL20, | en |
dc.relation.page | 45 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-02-07 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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