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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35407完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林宜玲 | |
| dc.contributor.author | Ho-Chun Yang | en |
| dc.contributor.author | 楊賀鈞 | zh_TW |
| dc.date.accessioned | 2021-06-13T06:51:29Z | - |
| dc.date.available | 2013-12-31 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-07-23 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35407 | - |
| dc.description.abstract | 當細胞受到病毒入侵時大多會產生第一型干擾素 (type I interferons)，這一類細胞激素會透過JAK-STAT這條訊號傳遞路徑，來活化自身與周圍的細胞進入抗病毒狀態。泛素化 (ubiquitination) 與去泛素化 (deubiquitination) 是細胞內重要的蛋白質修飾作用，可透過改變訊號傳遞分子的穩定性或是其活化態，來影響許多細胞內訊息傳遞。本實驗室試圖尋找參與在第一型干擾素對抗登革病毒訊息傳遞途徑中的去泛素酶，我們透過帶有簪子干擾性核醣核酸 (shRNAs) 的慢病毒株 (lentiviruses) ，針對人類基因體內已知的84組去泛素酶進行核酸干擾作用 (RNA interference) ，來研究當缺失這些基因下，細胞的第一型干擾素對抗登革病毒訊號傳遞路徑會受到怎樣的影響。在本篇論文中，我們研究Usp30這個去泛素酶對於第一型干擾素抗登革病毒作用的影響，Usp30已知是嵌插在細胞內粒線體外膜上的去泛素酶，已被報導能夠調節粒線體的外觀。我們發現當Usp30表現量下降時，第一型干擾素抑制登革病毒的作用會受到抑制，作用機制可能是透過加速終止STAT3訊號傳遞路徑。我們也發現，STAT3的磷酸化可被細胞內酪氨酸去磷酸酶 (protein tyrosine phosphatases) 來移除，而不是透過蛋白酶體 (proteasome)。有趣的是，我們發現到Usp30能夠與STAT3在粒線體外膜上形成複合體，而且當STAT3在受到干擾素活化下會受到單一泛素化 (mono-ubiquitination) 的修飾，並且此修飾作用能夠被Usp30移除。在本篇論文中，我們找到了一個正向調控STAT3訊號傳遞路徑的分子：Usp30透過與STAT3在粒線體外膜上形成複合體，來調控STAT3的酪氨酸磷酸化與單一泛素化修飾作用，因而影響了干擾素抑制登革病毒複製的能力。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-13T06:51:29Z (GMT). No. of bitstreams: 1 ntu-100-R98445119-1.pdf: 9198100 bytes, checksum: 464411229069196474fcf0e4fbe6ef26 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Title-------------------------Page number
口試委員審定書---------------- i 誌謝-------------------------- ii 中文摘要---------------------- iii Abstract---------------------- iv Introduction------------------ 1 Specific aims----------------- 9 Materials and methods--------- 10 Results----------------------- 19 Conclusion-------------------- 28 Discussion-------------------- 29 References-------------------- 34 Tables and Figures------------ 39 Appendix---------------------- 57 Title------------------------------------------------------Page number Table 1 Primers used in this study------------------------- 39 Table 2 Candidate genes identified from DUB screening------ 40 Title---------------------------------------------------------------Page number Fig. 1 Usp30 knockdown affects anti-DEN effects of IFN-------------- 41 Fig. 2 Usp30 is involved in IFNs signaling-------------------------- 42 Fig. 3 The cellular localization and deubiquitinating activity of constructed Usp30------------------------------------------- 43 Fig. 4 STAT3 phosphorylation is affected by Usp30 knockdown--------- 44 Fig. 5 The turnover of tyrosine phosphorylated STAT3 was accelerated in cells with reduced Usp30 expression---------- 45 Fig. 6 Usp30 regulates STAT3 tyrosine phosphorylation through a mechanism dependent on tyrosine phosphatases-------------- 46 Fig. 7 Usp30 interacts with STAT3 and mitochondrial localization of Usp30 is required for this interaction------------------- 47 Fig. 8 IFN-α triggers the mono-ubiquitination of STAT3, but not STAT1------------------------------------------------------------------------- 48 Fig. 9 Tyrosine phosphorylation of STAT3 is required for mono-ubiquitination--------------------------------------------------------- 50 Title----------------------------------------------------------------------------------Page number Fig. 10 Mono-ubiquitinated STAT3 could be detected in both of the cytoplasmic and nuclear fractions with IFN stimulation---------- 51 Fig. 11 Usp30 might remove mono-ubiquitin from STAT3------------------- 52 Fig. 12 Our current model about how Usp30 regulates STAT3--------------- 53 Fig. 13 Usp30 knockdown results in higher DEN replication----------------- 55 Fig. 14 STAT1 protein level was reduced in cells over-expressed Usp30------------------------------------------------------ 56 | |
| dc.language.iso | en | |
| dc.subject | 去泛素化酵素 | zh_TW |
| dc.subject | 登革病毒 | zh_TW |
| dc.subject | 第一型干擾素 | zh_TW |
| dc.subject | Dengue virus | en |
| dc.subject | type I interferon | en |
| dc.subject | Usp30 | en |
| dc.subject | Deubiquitinating enzyme | en |
| dc.title | 探討Usp30對於第一型干擾素對抗登革病毒能力的影響 | zh_TW |
| dc.title | To study the role of Usp30 in the anti-dengue activity of type I interferon | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳美如,黃麗華,廖經倫,蘇旨茂 | |
| dc.subject.keyword | 登革病毒,去泛素化酵素,第一型干擾素, | zh_TW |
| dc.subject.keyword | Dengue virus,Deubiquitinating enzyme,Usp30,type I interferon, | en |
| dc.relation.page | 70 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-07-25 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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