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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10396完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃偉邦(Wei-Pang Huang) | |
| dc.contributor.author | Ang-Yu Liu | en |
| dc.contributor.author | 劉昂宇 | zh_TW |
| dc.date.accessioned | 2021-05-20T21:26:14Z | - |
| dc.date.available | 2011-08-20 | |
| dc.date.available | 2021-05-20T21:26:14Z | - |
| dc.date.copyright | 2010-08-20 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-19 | |
| dc.identifier.citation | Baumeister, W., Walz, J., Zuhl, F., and Seemuller, E. (1998). The proteasome: paradigm of a self-compartmentalizing protease. Cell 92, 367-380.
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The conserved oligomeric Golgi complex is involved in double-membrane vesicle formation during autophagy. Journal of Cell Biology 188, 101-114. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10396 | - |
| dc.description.abstract | 泛素是種小而保守的蛋白質，普遍的被用來標定在真核生物中將要被蛋白脢體分解的異常構型蛋白質。細胞自噬則是真核生物中另一條降解蛋白質的路徑；透過由雙層膜包裹的細胞質所形成的自噬小體與細胞中的液胞或溶小體進行融合，細胞能有效的分解胞器以及蛋白質，以獲得養分應付充滿壓力的環境。已知在哺乳動物細胞中，被泛素所標定的蛋白質除了透過蛋白脢體分解外，也會形成蛋白質聚集體，堆積在細胞質當中，而這些蛋白質聚集體，已被證實能選擇性的透過細胞自噬所清除。這次研究，我們發現在酵母菌中泛素修飾並不會促進蛋白質形成聚集體，且泛素化的修飾不但不會促進蛋白質透過細胞自噬分解，反而扮演著抑制性的角色。我們同時發現，泛素的一個已知的突變能破壞泛素與大部分泛素結合區的交互作用，而這種泛素突變也喪失抑制細胞自噬分解蛋白質的作用。我們認為，透過泛素與某種未知蛋白質的交互作用，阻礙了泛素化蛋白質被自噬小體包裹的過程。這個發現，是泛素抑制細胞自噬分解作用的首件案例。 | zh_TW |
| dc.description.abstract | Ubiquitin is a small, conserved molecule among eukaryotes that serves as a tag for the breakdown of misfolded-proteins by the 26s proteasome in eukaryotes. Autophagy is another protein turnover process, which sequesters cytoplasm into double membrane vesicles, called autophagosomes. Subsequent fusion with the vacuole/lysosome mediates breakdown of proteins or organelles in eukaryotes facing stressful environments. In mammalian cells, ubiquitylated protein aggregates in cytosol associated with neural degeneration diseases were shown to be specific substrates for autophagic degradation. However, in this study, we showed that the ubiquitin modification does not trigger the formation of protein aggregates in saccharomyces cerevisiae. Moreover, we found that ubiquitylation impedes, instead promotes, the degradation of cytosolic proteins by starvation-induced autophagy in yeast. We also identified an ubiquitin mutant, which was previously shown defective in interacting with most known ubiquitin-binding domains (UBD), lost the delay on autophagic degradation of cytosolic proteins. We propose that the interaction of ubiquitin with an unknown factor prevents sequestration of ubiquitylated cytosolic soluble proteins into autophagosomes for degradation. This is the first report indicating that ubiquitylation of cargo proteins hinder their autophagic degradation. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T21:26:14Z (GMT). No. of bitstreams: 1 ntu-99-R97b41027-1.pdf: 1319910 bytes, checksum: f3ed7a28aa21ef108a1deb6b7bf6155a (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | CONTENTS
摘要…………………………………………………………………………………..i ABSTRACT………………………………………………………………………ii INTRODUCTION Overview of the UPS pathway……………………………………………………1 Overview of autophagy…………………………….……………………………….5 The selectivity of autophagy………………………………………………………..9 MATERIALS AND METHODS Strains and Media………………………………………………………………….13 Plasmid construction………………………………………………………………13 Western blot analysis………………………………………………………………15 Fluorescent microscopy analysis…………………………………………………..16 Inhibition of proteasome activity with the treatment of MG132………………......16 RESULTS Ubiquitylation does not trigger protein aggregation in yeast………………….......17 Ubiquitylated EGFP is a substrate for autophagic degradation……………………20 Proteasomes, but not autophagy, degrade most ubiquitylated EGFP during starvation……………………………………………………………………………..21 Autophagic degradation of UbG76V-EGFP was slower than that of UbI44A,G76V-EGFP…………………………………………………………………….23 Low level of ubiquitylated EGFP is not a substrate for autophagic degradation….26 Delay of ubiquitylated EGFP in autophagic degradation is not unique to specific genetic background………………………………………………………….27 Autophagic degradation of ubiquitylated EGFP is slower than that of other cytosolic proteins…………………………………………………………………...28 DISCUSSION Ubiquitylation triggers no protein aggregation in yeast…………………………...32 Delay, rather than acceleration, of UbG76V-EGFP in autophagic degradation……..32 Low level of ubiquitylated EGFP is not a substrate for autophagy………………..34 I44A mutation destroys the delay of ubiquitylation in autophagic degradation of cytosolic protein……………………………………………………………………...34 The competition between proteasome and autophagy for UbG76V-EGFP as a substrate………………………………………………………………………………35 The first report that ubiquitylation hinders autophagic degradation of cytosolic soluble proteins………………………………………………………………………38 REFERENCES…………………………………………………………………41 TABLES…………………………………………………………………………..52 FIGURES…………………………………………………………………………53 | |
| dc.language.iso | en | |
| dc.title | 泛素化在細胞自噬分解酵母菌胞內蛋白質中
所扮演的角色 | zh_TW |
| dc.title | Role of ubiquitylation in autophagic degradation of cytosolic soluble protein in Saccharomyces cerevisiae | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳俊宏(Jiun-Hong Chen),李心予(Hsin-yu Lee),朱家瑩(Chia-Ying Chu) | |
| dc.subject.keyword | 泛素, | zh_TW |
| dc.subject.keyword | Ubiquitin,Ubiquitylation,Autophagy, | en |
| dc.relation.page | 65 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2010-08-19 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究所 | zh_TW |
| 顯示於系所單位： | 動物學研究所 | |
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