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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 嚴仲陽 | |
| dc.contributor.author | Han-Jou Chen | en |
| dc.contributor.author | 陳菡柔 | zh_TW |
| dc.date.accessioned | 2021-06-13T06:39:45Z | - |
| dc.date.available | 2005-08-18 | |
| dc.date.copyright | 2005-08-18 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2005-08-02 | |
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Cancer Res. 63, 705-712 (2003) Devireddy, L. R., Teodoro, J. G., Richard, F. A. and Green, M. R. Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science 293, 829-934 (2001) | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35053 | - |
| dc.description.abstract | 在哺乳動物，造血細胞（hematopoietic cell）的生長需要依靠特定的細胞素（cytokines），然而這些細胞素不僅讓細胞生長分化，它們亦會抑制細胞凋亡（apoptosis）以維持細胞的存活。當細胞素自培養液中移除，細胞會走向細胞凋亡，而這種死亡的路徑被證明需要新合成的RNA和蛋白質參與其中。我們的目標即在於研究參與在這條細胞凋亡路徑的分子。因此，本實驗室先前已利用DNA晶片分析比較依賴細胞素的TF-1細胞在給予及去除細胞素時的RNA表現差異，發現TRB2基因在細胞缺少細胞素時表現較正常培養時高出約兩倍。進一步的研究顯示，在小鼠和人類依靠細胞素的細胞中大量表現TRB2，或以RNAi的方式降低TRB2的量，都可證明TRB2確實參與在造血細胞的細胞凋亡途徑。
對於這些細胞素去除所誘導表現的基因，我們目前對其調控機制所知甚少，故此，本研究的主要目標即在於了解TRB2是如何被調控。首先，我們比較人類TRB2基因在各組織器官的表現情形，並以北方轉漬法，更確認TRB2 RNA在TF-1細胞缺乏細胞素（GM-CSF）二十四小時累積達到最大量。進一步，使用primer extension和5’ RACE，我們也找出TRB2 RNA可能的轉錄起始點。另外藉由篩選人類基因組，找出TRB2 5’端的DNA片段，並將其選殖進報導基因載體（reporter vector），初步鑑定出TRB2基因轉譯點上游2kb的區域可能具有基本的啟動子活性，同時也可能包含受細胞素調控的片段。最後，藉由篩選老鼠基因組，我們已將老鼠TRB2 第一個表現子附近的基因序列選殖出來，用以建構基因剔除載體，並已產生TRB2基因剔除的嵌合小鼠；未來將獲得的TRB2基因缺乏小鼠將幫助我們更進一步了解TRB2所扮演的生理功能。 | zh_TW |
| dc.description.abstract | In mammals, the development of hematopoietic system depends on cytokines. These cytokines not only mediate cell proliferation and differentiation, but also enhance the survival of these cells by the suppression of apoptotic pathways. Once the cytokines are deprived, cells undergo apoptosis which has been proved to require de novo RNA and protein synthesis, suggesting that new genes are required to proceed the apoptotic signaling pathway. Our goal is to identify the molecules participating in cytokine withdrawal-induced apoptosis of hematopoietic cells. To achieve this goal, our laboratory used microarray to discover the Drosophila tribbles homolog 2 (TRB2) gene that is up-regulated during cytokine withdraw in the cytokine-dependent TF-1 cell line. Further studies using over-expression and RNA interferences technique strongly suggest that TRB2 indeed participating in cytokine withdrawal-induced apoptosis
Since it is little known about the regulation of cytokine withdrawal-induced genes, the aim of this study is to investigate the regulation of TRB2. In the beginning of this thesis, the human tissue distribution of TRB2 were determined. The accumulated TRB2 RNA level was found to achieve the highest level 24 h after cytokine withdraw. Primer extension and 5’ RACE (rapid amplification of cDNA ends) were then performed to identify the transcription start site of human TRB2. We also performed reporter assay to find that the 2-kb fragment upstream of the translation start site may contain the basal promoter activity and cytokine withdrawal-responsive element. Finally, the mouse genomic library was screened for targeting vector construction. The TRB2 knockout mice are intended to be generated for understanding the physiological functions of TRB2. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T06:39:45Z (GMT). No. of bitstreams: 1 ntu-94-R92448003-1.pdf: 1081200 bytes, checksum: 59ba849ce28b7490085d1c61c9590191 (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | Abbreviation table....................................................1
Abstract.....................................................................2 Introduction...............................................................4 1. Programmed Cell Death..................6 2. Cytokine withdrawal-induced apoptosis....8 3. Tribbles.................................9 4. Specific aims............................11 Materials and Methods............................................11 1. Materials................................13 2. Methods..................................16 Results......................................................................20 1. Tissue distribution of TRB2 gene.............................................22 2. Transcriptional regulation of TRB2...........................................22 3. Cloning of the human TRB2 promoter region............................23 4. Identification the transcriptional start site(s) of human TRB2....24 5. Functional analysis of the human TRB2 promoter.....................25 6. Preparation of TRB2 knock out mice.........................................26 Discussion................................................................25 Acknowledgements.................................................31 References................................................................32 Figures......................................................................39 | |
| dc.language.iso | en | |
| dc.title | 分子選殖及鑑定人類TRB2基因啟動子區域 | zh_TW |
| dc.title | Molecular cloning and characterization of human TRB2 gene promoter region | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 93-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李方仁,阮麗蓉 | |
| dc.subject.keyword | 啟動子, | zh_TW |
| dc.subject.keyword | cytokine withdraw,TRB2,tribbles,apoptosis,hemopoietic cells, | en |
| dc.relation.page | 55 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-08-02 | |
| 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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