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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 繆希椿教授 | |
| dc.contributor.author | Yi-Li Cho | en |
| dc.contributor.author | 卓益立 | zh_TW |
| dc.date.accessioned | 2021-06-15T06:19:51Z | - |
| dc.date.available | 2020-12-31 | |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-10 | |
| dc.identifier.citation | 1. Billiau A, Matthys P. Interferon-γ : A historical perspective. Cytokine & Growth Factor Reviews. 2009;20:97-113.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47809 | - |
| dc.description.abstract | Runx 家族蛋白皆含有一段與異二聚體Cbfβ鍵結的保守區塊，Runt 區域。Runx家族蛋白並有三個成員Runx1，Runx2 和Runx3。Runx3 是家族中分子量最小的蛋白質，主要表現於第一型輔助細胞及細胞毒殺細胞中，更與轉錄因子T-bet 共同參與活化第一型干擾素的表現。然而，Runx3 蛋白中與T-bet 相互作用的區域及其參與調控第一型干擾素表現的機制尚待進一步探討。
中研院基因突變鼠核心實驗室所建立的P054 突變鼠含有C 端105 個胺基酸缺失的Runx3 蛋白，初步研究發現P054 小鼠的週邊淋巴器官有異常的CD4/CD8 細胞族群表現。進一步研究顯示P054 突變鼠的第一型輔助細胞及細胞毒殺細胞的第一型干擾素表現皆有減少的趨勢。由此可知 C 端胺基酸缺失的Runx3 蛋白是調控淋巴細胞發育及功能的重要元素。然而，突變的Runx3 蛋白並未造成細胞分布及蛋白質穩定性的異常。此外，深入探討得知 NMTS 區域是與T-bet 作用共同驅動第一型干擾素活化的主要區塊。總結以上結果推論 Runx3 蛋白中的NMTS 區域可能是參與淋巴細胞發育及第一干擾素表現的重要元素。 | zh_TW |
| dc.description.abstract | Runx proteins, which contain a conserved Runt domain, are a heterodimer bound with cofactor, Cbfβ. Runx family contains three members, Runx1, Runx2, and Runx3. Runx3, the smallest protein of the family, mainly expressed in effector CD4+ Th1 cells and CD8+ T cells and cooperates with T-bet to activate IFN-γ gene expression. However, which domain(s) of Runx3 interacts/interact with T-bet to drive IFN-γ expression remains unknown. P054 mice, generated from ENU core in Academia Sinica, have a truncated Runx3 protein with 105 amino acid deletion in C-terminal. We observed abnormal profile of CD4/CD8 expression in P054 mice. Furthermore, decreased IFN-γ productions were identified in Th1 and CD8 of P054 mice. It indicates that the deleted C-terminal domain of Runx3 is important in T cell development and their effecor functions. However, loss of Runx3 C-terminal still maintains its cellular localization and protein stability. In addition, we observed that the NMTS domain of Runx3 is an important domain to cooperate with T-bet for the activation of IFN-γ. Take together, The NMTS domain of Runx3 might play a important role in lymphoid cell development and IFN-γ production. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T06:19:51Z (GMT). No. of bitstreams: 1 ntu-99-R97449006-1.pdf: 1527941 bytes, checksum: 294a8342f87a4b50d85e8aa1665b6e47 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | Abstract ii
摘要 iii Table of Contents iv List of Figures vi Chapter I Introduction 1 I. Overview of Interferon-γ 1 II. Development and Differentiation of Lymphoid Lineage Cell Populations 3 III. Runx Family 6 IV. The Regulations of Runx Protein in T Cell Lineage 7 V. Runx proteins nd Diseases 9 VI. Rationales 10 Chapter II Materials and Methods 12 I. Experimental Marials 12 1.1 Mice 12 1.2 Promoter and Expression Constructs 12 1.3 Chemicals and Reagents 14 1.4 Enzymes, Cytokines and Antibodies 17 1.5 Media, Solutions and Buffers 20 1.6 Commercial Kits 28 1.7 Instruments and Softwares 29 II. Experimental Methods 31 1.1 In vitro T cell differentiation and stimulation 31 1.2 IFN-γ induction of NK and NKT cells 31 1.3 Intracellular Cytokine Staining (ICS) 32 1.4 Enzyme-Linked Immunosorbent Assay (ELISA) 32 1.5 Luciferase assay 33 1.6 Protein stability analysis 33 1.7 Confocal microscopy 34 1.8 Nuclear Matrix-Intermediate Filament Extraction 34 1.9 Statistical Analysis 35 Chapter III Results 36 I. Truncated Runx3 Leads to Abnormal expression of Lymphoid cell population 36 II. Lower IFN-γ Expression in Lymphoid Cells of Runx3-Truncated Mice 38 III. Comparable Protein Stability and Cellular Distribution of Runx3 in P054 Mice 39 IV. NMTS Domain of Runx3 Is The Major Binding Site of T-bet to Cooperatively Regulate IFN-γ 40 Chapter IV Disscussions 43 Chapter V Figures 50 Chapter VI References 63 Appendix 68 | |
| dc.language.iso | en | |
| dc.title | Runx3調控丙型干擾素的探討 | zh_TW |
| dc.title | Characterization of Runx3-modulated IFN-γ expression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 伍安怡教授,孔祥智教授 | |
| dc.subject.keyword | 丙型干擾素, | zh_TW |
| dc.subject.keyword | Runx3,IFN-γ, | en |
| dc.relation.page | 69 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-08-10 | |
| 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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