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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳光超 | |
| dc.contributor.author | Yi-Ting Wang | en |
| dc.contributor.author | 王怡婷 | zh_TW |
| dc.date.accessioned | 2021-06-16T02:28:07Z | - |
| dc.date.available | 2020-08-31 | |
| dc.date.copyright | 2015-08-31 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-03 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53712 | - |
| dc.description.abstract | 細胞自噬(Autophagy)作用是真核生物演化上高度保留的代謝途徑。當細胞面對飢餓、缺氧與氧化等壓力時，細胞自噬反應透過溶酶體(lysosome)降解細胞內不需要、堆疊之蛋白質與老化、損壞的胞器等以維持細胞內之平衡。Atg9是目前所有細胞自噬相關蛋白中唯一的穿膜蛋白，其在細胞自噬反應中扮演攜帶、提供磷脂雙層膜的角色。在實驗室先前研究中，發現Atg9和TRAF6的交互作用可活化氧化物壓力所引誘之JNK活性及細胞自噬。TRAF6也可透過調節Beclin 1 泛素化(ubiquitination)引起細胞自噬反應。然而Atg9、TRAF6和Beclin 1之間的關係到目前仍然不清楚。在本研究中，我們發現Atg9和Beclin 1有交互作用，且此交互作用在有TRAF6存在的情況下會變得更強烈。Beclin 1會和PI3K/Vps34結合並調控細胞自噬與胞吞作用(endcytosis)。在本研究中，我們發現細胞在沒有Atg9或TRAF6的情況下，和細胞沒有Beclin 1 的情況相同都會使EGFR的降解作用會降低。因此我們認為Atg9和TRAF6和 Beclin 1一樣都可參與胞吞作用的調節。我們將再進一步探討 TRAF6-mAtg9-Beclin 1在細胞自噬與胞吞作用中的分子機制。 | zh_TW |
| dc.description.abstract | Autophagy is a highly conserved and tightly regulated catabolic process that digests and recycles cellular components such as aggregated proteins or damaged organells through lysosomes in response to environmental stresses. Atg9 is the only known transmembrane protein among autophagy-related proteins and thought to act as a lipid carrier during autophagosome formation. Our recent work showed that Atg9 interacts with TRAF6 to regulate oxidative stress-induced JNK signaling and autophagy induction. TRAF6 has been shown to regulate lysine 63-linked ubiquitination of Beclin1 to induce autophagy. However, the relationship between Atg9, and the interaction is enhanced when TRAF6 is overexpressed. However, TRAF6-mediated Beclin 1 ubiquitination is not responsible of the enhanced interaction between Atg9 and Beclin 1. It has been shown that Beclin1- PI3K/Vps34 complex regulates autophagy as well as endocytosis. We found that depletion of Atg9 or TRAF6 attenuates EGFR degradation, suggesting that like Beclin 1, Atg9 and TRAF6 also plays a role in endocytic trafficking. We will further investigate the molecular mechanisms underlie TRAF6-Atg9-Beclin 1-mediated autophagy and endocytosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T02:28:07Z (GMT). No. of bitstreams: 1 ntu-104-R02b46011-1.pdf: 5682139 bytes, checksum: 2c40daf650ec823d053423c9ec70c83f (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 中文摘要 1 ABSTRAT 2 INTRUDUCTION 3 1. Overview of Autophagy 3 2. The machinery of Autophagy 4 (1) The Atg1/ULK1 protein kinase complex 5 (2) Becln1-class III PI3K complex 5 (3) Two ubiquitin-like conjugation systems 7 (4) Atg9 and other autophagy related proteins 8 3. TNF receptor-associated factor 6 (TRAF6) 11 4. Endocytosis and autophagy 14 MATERIALS AND METHODS 17 RESULT 23 1. Atg9 interacts with Beclin1 through Beclin 1 23 2. The interaction of Atg9 and Beclin 1 is enhanced in the early stage of autophagy 24 3. TRAF6 regulates Atg9-Beclin 1 interaction 25 4. The catalytic activity of TRAF6 is required for the interaction between Ag9 and Beclin 1 26 5. Beclin 1 KR mutant interacts with Atg9 27 6. TRAF6 regulates Atg9 ubiquitination 28 7. Beclin1, Atg9 or TRAF6 regulate endocytic trafficking 29 DISCUSSION 32 REFERENCES 35 FIGURES 40 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討Atg9蛋白在細胞自噬及胞吞作用之分子機轉與功能 | zh_TW |
| dc.title | Molecular characterization and functional analysis of Atg9 in autophagy and endocytosis. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳瑞華,楊維元 | |
| dc.subject.keyword | 細胞自噬,胞吞作用,Atg9,Beclin 1,TRAF6, | zh_TW |
| dc.subject.keyword | Autophagy,Endocytosis,Atg9,Beclin 1,TRAF6, | en |
| dc.relation.page | 54 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-03 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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