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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳瑞華 | |
| dc.contributor.author | Yi-Ru Chen | en |
| dc.contributor.author | 陳奕如 | zh_TW |
| dc.date.accessioned | 2021-06-13T06:38:58Z | - |
| dc.date.available | 2005-08-18 | |
| dc.date.copyright | 2005-08-18 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2005-08-09 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35020 | - |
| dc.description.abstract | 真核生物轉譯因子3k（eIF3k），分子量約28kDa，為真核生物之轉譯相關分子群中最小的亞分子。eIF3k在不同的物種間具有高度的演化保守性，在人類、小鼠、線蟲以及阿拉伯芥中均可找到同源相似物。在本篇論文中，我們並未觀察到eIF3k在一般轉譯過程中扮演著必要的角色，但卻發現了eIF3k具有另一特殊功能在細胞凋亡的調控上。首先，利用小片段干擾核甘酸 (siRNA) 抑制eIF3k的表現，發現可以降低細胞對死亡刺激的反應，這些刺激包括UV損傷以及STS (staurosporine)。更進一步，我們接櫫eIF3k影響細胞凋亡的分子機制。利用螢光蛋白標定及Trtiton 生化萃取分析，我們觀察到大部分的eIF3k會座落於角質蛋白8號 (K8) 和18號 (K18) 所共同組成的中間細絲網路 (intermediate filaments)。我們也證實這樣的現象是由於eIF3k和K8/K18會相互結合，不僅在利用免疫沉澱技術 (immunoprecipiation) 或酵母菌雙雜交系統 (yeast two hybrid) 的實驗上亦然。文獻指出，在細胞凋亡的過程中，K8/K18所形成的中間細絲網路會先崩塌形成包含體 (intracellular inclusion)，之後，在細胞凋亡晚期則存在於細胞的cytoplasmic blebs。並且K8/K18會藉由和一些引發細胞凋亡的前驅分子有交互作用，進而調控細胞的死亡，我們因而推測eIF3k是否也藉由K8/K18而影響了細胞的計劃性死亡。因此在機制的剖析中，我們證明了eIF3k的存在與否會影響活化caspases在細胞凋亡過程中在細胞內的分布情形。所以我們初步推論， eIF3k對細胞凋亡的影響，主要藉由和活化的caspases共同競爭與K8/K18間的結合，進而改變活化的caspases在細胞中的分佈，而影響了caspases 和受質間作用的機會。 | zh_TW |
| dc.description.abstract | eIF3k, a 28 kDa protein, is the smallest subunit of eukaryotic translation initiation factor 3 complex and is evolutionally conserved among higher eukaryotes, including mammals, insects, worms and plants. However, genetic and biochemical studies failed to demonstrate an essential role of eIF3k in general translation. Here, we identified a novel function of eIF3k in promoting apoptosis, as knockdown of endogenous eIF3k could de-sensitize cells to several apoptotic stimuli, such as UV irradiation | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T06:38:58Z (GMT). No. of bitstreams: 1 ntu-94-R92448001-1.pdf: 1856968 bytes, checksum: bd5e09fd86a34f628977c318f8638a28 (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | Table of content 1
Abstract 3 中文摘要 4 Introduction 5 Apoptosis 5 Keratin intermediate filaments 9 Keratin intermediate filaments and apoptosis 11 eIF3k 15 Material & Methods 19 Cell lines and reagents 19 Induction of apoptosis 19 Western blotting and Antibodies 20 Immunofluorescence microscopy 20 FACS analysis 21 Yeast two-hybrid assay 21 Immunoprecipitation 22 Metabolic labeling 22 BrdU ELISA assay 23 Detergent extraction assay 23 FRET (Fluorescence resonance energy transfer) 24 Results 25 siRNA generation to knockdown eIF3k expression. 25 The effect of eIF3k in protein synthesis 26 The effect of eIF3k in cell growth 26 eIF3k’s function in apoptosis regulation 27 eIF3k colocalizes with the cytokeratin 8/18 28 eIF3k directly interacts with K18 in yeast 28 eIF3k associates with K8/K18 in vivo 29 The association of eIF3k with cytokeratin 8/18 filament proved by FRET image analysis 29 Endogenous eIF3k and K8/18 interact with each other. 30 The formation of eIF3k granular structure during apoptosis is caspase 3-dependent 31 eIF3k affects caspase distribution in Triton-soluble cytosolic fraction and Triton-insoluble cytoskeleton fraction. 32 Discussion 34 Reference List 39 Figures 46 Figure 1. Sequence alignment of eIF3k 46 Figure 3. A proposed model for the function of Ced-X. 48 Figure 4. eIF3k siRNA knockdowns the endogenous level of eIF3k. 49 Figure 5. Knockdown of eIF3k would not affect global protein synthesis. 50 Figure 6. Over-expression of eIF3k would not affect global protein synthesis. 51 Figure 7. Knockdown of eIF3k would not affect cell growth. 52 Figure 8. eIF3k knockdown attenuates UV-induced apoptosis.. 53 Figure 9. eIF3k knockdown attenuates Staurosporine(STS)-induced apoptosis.. 54 Figure 10. eIF3k subcellular localization 55 Figure 11. Interaction of eIF3k and K18 in yeast two-hybrid system. 56 Figure 12. eIF3k interacts with K18 in vivo. 57 Figure 13. eIF3k forms a complex with K8 in vivo. 58 Figure 14. Use of FRET methodology to assess in vivo protein interaction 59 Figure 15. Interaction of endogenous eIF3k with endogenous K8/K18 60 Figure 16. The eIF3k granular structures are caspase 3 dependent. 61 Figure 17. eIF3k affects caspase distribution in Triton-soluble cytosolic fraction and Triton-insoluble cytoskeleton fraction. 62 Figure 18. A proposed model for the function of eIF3k. 63 Appendix 64 Appendix I. The effect of eIF3k SiRNA in apoptosis is not observed in cells without cytokeratin 64 | |
| dc.language.iso | en | |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 角質蛋白8號 (K8) 和18號 (K18) | zh_TW |
| dc.subject | 真核生物轉譯因子3k | zh_TW |
| dc.subject | Apoptosis | en |
| dc.subject | eIF3k | en |
| dc.subject | cytokeratin K8/K18 | en |
| dc.title | eIF3k 調控細胞凋亡之分子機制與功能探討 | zh_TW |
| dc.title | Study of The Function and Molecular Mechanism of eIF3k in Apoptosis Regulation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 93-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 呂勝春,許秉寧 | |
| dc.subject.keyword | 真核生物轉譯因子3k,細胞凋亡,角質蛋白8號 (K8) 和18號 (K18), | zh_TW |
| dc.subject.keyword | eIF3k,cytokeratin K8/K18,Apoptosis, | en |
| dc.relation.page | 64 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-08-10 | |
| 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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