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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賴明宗(Ming-Zong Lai) | |
| dc.contributor.author | Yu-Hsuan Yang | en |
| dc.contributor.author | 楊鈺璇 | zh_TW |
| dc.date.accessioned | 2021-06-14T16:51:52Z | - |
| dc.date.available | 2011-09-11 | |
| dc.date.copyright | 2008-09-11 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-30 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40574 | - |
| dc.description.abstract | Notch 訊息的傳遞可以調控多項生物性功能，而已知Notch可藉由活化PI3K-Akt的訊息傳遞調控細胞凋亡。但目前對於Notch如何活化PI3K-Akt訊息並不清楚。在本研究中，我們探討Notch 活化 Akt 的幾個可能途徑: ㄧ個是透過Notch本身的轉錄能力，另ㄧ個藉由先活化Lck ，第三個則經由XIAP的訊息，而造成Akt 之活化。我們先在利用Notch配體Jagged 1與DLL1 刺激DO11.10 與NIH3T3 細胞皆可造成 Akt 的活化。證實Notch 的活化確實能誘導 Akt 的活化。在Notch 活化 Akt 是否透過轉錄活性方面，我們使用不同NICD的突變型。在探討Lck的參與方面，我們利用Lck抑制劑阻斷Lck的活化，觀察Akt活化是否受影響。在分析XIAP角色的方面，我們大量表現XIAP或下調細胞內的XIAP，研究其對Akt活化的影響。我們發現Notch 活化 Akt於DO11.10和NIH3T3細胞有些不同。Notch在DO11.10細胞活化Akt涉及Notch的轉錄活性，也需要Lck的參與，而XIAP的存在也是需要的。Notch在NIH3T3細胞則除利用其轉錄活性參與之外，不具轉錄活性的TAD也可以尚未清楚的機制活化Akt，但XIAP則未參與Notch活化Akt。我們的結果顯示了多種訊息分子參與了Notch引發Akt的活化，而詳細的活化機制需要更近一步的探討。 | zh_TW |
| dc.description.abstract | Notch signaling regulate several key biological functions, Notch inhibits apoptosis through activation of PI3K-Akt signaling. The mechanism how Notch activates PI3K-Akt remains unclear. In this study, we examined three possible mechanisms involved in the activation of Akt by Notch. First, Notch may activate Akt through transcription activation of target genes. Second, Notch may activate Lck for subsequent activation of Akt. Third, Notch may stimulate Akt through enhanced XIAP signaling. We first used Notch ligands Jagged1 and Delta-like ligand1(DLL1) to stimulate DO11.10 T cell hybridoma and NIH3T3 fibroblast, and detected Akt phosphorylation, confirming the capacity of Notch to activate Akt.
To determine the requirement of Notch transcription activity, we used different mutants carrying truncated forms of Notch intracellular domain (NICD). To study the potential involvement of Lck, Notch induced Akt activation was evaluated by using Lck inhibitor to block Lck activation. To investigate the possible involvement of XIAP, effect on Akt activation was determined when XIAP was either overexpressed or downregulated. We found similarity and difference between DO11.10 and NIH3T3 cells on the activation of Akt by Notch. In DO11.10 cells, the activation of Akt by Notch requires the transcription activity of Notch, Lck activation, and presence of XIAP. In NIH3T3 cells, the activation of Akt by Notch is involved the transcription activity of Notch and its transcription-inactive TAD domain, acting in unknown mechanism, but not XIAP. Our results illustrate the involvement of multiple signaling molecules in Notch-stimulated Akt activation, and point to the necessity for further investigation the detailed activation mechanisms. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-14T16:51:52Z (GMT). No. of bitstreams: 1 ntu-97-R95449011-1.pdf: 2297447 bytes, checksum: b7a09e2b7aa05d971431763fa14f5d4b (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 中文摘要..................................................i
英文摘要.................................................ii 目錄.....................................................iv 第一章 序論.............................................1 1.1.1 Notch 簡介......................................1 1.1.2 Notch調節細胞育 (development)及分化 (differentiation)...............................3 1.1.3 Notch 與致癌基因 (oncogene).....................4 1.2.1 Akt 簡介........................................6 1.2.2 PKB/Akt 活化的調節..............................7 1.2.3 Akt 調節細胞死亡 (cell death)...................7 1.3 研究目的與研究方向..............................8 第二章 實驗材料與方法..................................11 2.1 細胞株及其培養...................................11 2.2 藥品與試劑.......................................11 2.3 抗體.............................................12 2.4 小分子干擾核醣核酸下調 (siRNA knockdown).........12 2.4.1小分子干擾核醣核酸設計與質體構築................13 2.4.2 Lentivirus 反轉錄病毒製備......................14 2.4.3 Lentivirus 反轉錄病毒效價測定..................16 2.4.4 Lentivirus 反轉錄病毒感染......................17 2.5 固著式Notch 配體活化Notch 受體...................17 2.6 質體 DNA的轉染 (transfection)....................18 2.6.1 Calcium phosphate..............................18 2.6.2 電穿孔法(electroporation)......................18 2.6.3 反轉錄病毒感染法 (retroviral infection)........19 2.7 細胞萃取液的製備.................................20 2.8 西方墨點法 (Western blot)........................20 2.9 重組蛋白質純化 (purification of recombinant proteins)........................................21 第三章 結果............................................22 3.1 固著式 Notch 配體在 DO11.10 中可活化 Notch 訊息..22 3.2 Notch配體的刺激於 DO11.10 細胞與 NIH3T3 細胞中皆可 誘導Akt活化.......................................22 3.3 TAD domain 的轉錄能力是Notch在 DO11.10 細胞活化 Akt所需要.........................................24 3.4 Notch在 NIH3T3 細胞可藉由轉錄能力或TAD本身活化Akt25 3.5 大量表現NICD於 DO11.10 細胞中可誘導 Lck 活化.....25 3.6 抑制 Lck 的訊息傳遞同時阻斷Notch 活化 Akt 的訊息傳 遞...............................................25 3.7 於DO11.10 細胞與 NIH3T3細胞中大量表現野生型 (WT) 與突變型 XIAP不會誘導 Akt 活化...................26 3.8 XIAP siRNA 成功下調 NIH3T3 細胞內生性 XIAP.......27 3.9 下調XIAP 延遲 Notch在NIH3T3 細胞中誘導的Akt活化..28 3.10下調 XIAP抑制Notch在DO11.10 細胞中誘導的Akt活化..29 第四章 討論............................................30 圖表.....................................................35 參考資料.................................................53 附錄.....................................................64 | |
| dc.language.iso | zh-TW | |
| dc.subject | Akt 活化 | zh_TW |
| dc.subject | Notch 訊息傳遞 | zh_TW |
| dc.subject | Notch | en |
| dc.subject | Akt activation | en |
| dc.title | 探討Notch訊息活化Akt之機制 | zh_TW |
| dc.title | Study on the mechanism of the Notch-mediated Akt activation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許秉寧,繆希椿 | |
| dc.subject.keyword | Notch 訊息傳遞,Akt 活化, | zh_TW |
| dc.subject.keyword | Notch,Akt activation, | en |
| dc.relation.page | 66 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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