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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 繆希椿 | |
| dc.contributor.author | Wan-Chen Cheng | en |
| dc.contributor.author | 程婉珍 | zh_TW |
| dc.date.accessioned | 2021-06-16T22:59:08Z | - |
| dc.date.available | 2017-09-18 | |
| dc.date.copyright | 2012-09-18 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-08 | |
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Id entification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. Proceedings of the National Academy of Sciences of the United States of America 94, 6746-6751 (1997). 52. Javed, A. et al. Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription. Journal of cell science 113 ( Pt 12), 2221-2231 (2000). 53. Cruz-Guilloty, F. et al. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. The Journal of experimental medicine 206, 51-59 (2009). 54. Djuretic, I.M. et al. Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nature immunology 8, 145-153 (2007). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64780 | - |
| dc.description.abstract | 研究指出轉錄因子c-Maf在第二型輔助T細胞(Th2)當中能夠調控介白素四(IL-4)的基因表現，在我們實驗室之前的研究發現酪胺酸磷酸化與SUMO化的轉譯後修飾，都是調控轉錄因子c-Maf功能重要的一環，經由SUMO化修飾會減弱c-Maf所調控的介白素四 (IL-4)的表現，以及經由酪胺酸磷酸化修飾的c-Maf則會增強介白素四的表現，在其他的研究指出c-Maf 在輔助型T淋巴球當中能夠調控介白素十 (IL-10)、介白素二十一 (IL-21)與介白素二十二 (IL-22)的表現。在我的實驗當中發現在小鼠T淋巴瘤细胞 (EL4 cells)當中，經由酪胺酸磷酸化修飾的c-Maf會增強介白素十的表現，並且利用染色質沉澱技術 (chromatin immunoprecipitation analysis)發現c-Maf的酪胺酸磷酸化對介白素十的啟動子有較強的DNA結合能力，而在第十七型輔助T細胞 (Th17)也發現c-Maf的酪胺酸磷酸化會增強介白素十與介白素二十一的表現。 | zh_TW |
| dc.description.abstract | c-Maf was discovered as a transcription factor of IL-4 to regulate Th2-specific Il4 gene expression. Previous studies in our lab has shown that post-transcriptional modifications, such as tyrosine-phosphorylation and SUMOylation, are important to regulate c-Maf function. Furthermore, SUMOylation attenuates c-Maf-dependent IL-4 expression. Whereas, the tyrosine-phospholated c-Maf enhances the IL-4 production. c-Maf mediates IL-21, IL-10 and IL-22 expression in Th cells. In this study, we domostrate that the phosphorylation of c-Maf enhances the IL-10 production in EL4 cells through increases the c-Maf DNA binding ability. In taddition, the IL-10 and IL-21 production are enhanced by phosphorylated c-Maf in Th17 cells.
| en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T22:59:08Z (GMT). No. of bitstreams: 1 ntu-101-R99449010-1.pdf: 1353461 bytes, checksum: e03fbece91a425370d86603960a2fca9 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 中文摘要 i
Abstract ii Chapter 1. Introduction 1 1.1 SUMO-a reversible post-translational protein modifier 1 1.2 Tyrosine phosphorylation 2 1.3 The differentiation of Th17 cells 3 1.4 An overview of c-Maf 4 1.5 Rationale and approaches 6 Chapter 2. Experimental Materials 7 2.1 Mice 7 2.2 Chemicals and Reagents 7 2.3 Enzymes and Cytokines 10 2.4 Antibodies 11 2.5 Kits 11 2.6 Medium, solutions and buffers 12 2.7 Vectors 16 Chapter 3. Experimental Methods 17 3.1 Cell culture, transfection and electroporation 17 3.2 In vitro Th17 cells differentiation and stimulation 17 3.3 Intracellular cytokine staining 18 3.4 Preparation of retroviruses 18 3.5 Retrovious transduction 19 3.6 Chromatin immunoprecipitation assay 19 3.7 Quantitative PCR analysis 21 3.8 Statistical analysis 21 Chapter 4. Results 22 4.1 The phosphorylation of c-Maf enhances the IL-10 and IL-21 production in Th17 cells. 22 4.2 The phosphorylation of c-Maf influence the IL-10 and IL-21 production probably through DNA binding ability in Th17 cells. 24 Chapter 5. Discussion 26 5.1 The SUMOylation of c-Maf attenuates the IL-4 production and the phosphorylation of c-Maf enhances the IL-4 production throuth DNA binding. 26 5.2 K33R c-Maf did not influence IL-10 and IL-21 mRNA expression level in Th17 cells. 27 5.3 IL-22 mRNA could not be detected in Th17 cells. 27 5.4 The tyrosine-phosphorylation and SUMOylation of c-Maf may influence the IL-10 and IL-21 mRNA expression in Tr1 cells. 29 Figures 30 Figure 1. IL-17, IFN-γ and IL-4 were analyzed by flow cytometry for Th17 skewing cells. 30 Figure 2. Construction of pMIGRI-HA-c-Maf-flag series. 31 Figure 3. Expression of pMIGRI-HA-flag, pMIGRI-HA-c-Maf-flag and pMIGRI-HA-Y3F c-Maf-flag in EL4 cells. 33 Figure 4. The Il4 and Il10 genes expression after WT c-Maf, Y3F c-Maf electroporation in EL4 cells. 35 Figure 5. The Il10 and Il21 genes expression in WT c-Maf, Y3F c-Maf or K33R c-Maf retroviral transducted in Th17 cells. 37 Figure 6. The diagram of experimental design. 38 Figure 7. DNA fragments product by sonication. 39 Figure 8. The primer design of Il10, Il21 and Il22 promoter to perform the ChIP assay. 40 Figure 9. The phosphorylation of c-Maf affect IL-4 and IL-10 production through DNA binding ability in EL4 cells. 42 Figure 10. Construction of GFP-RV-c-Maf-flag series. 43 References 44 Part 2 52 Characterization of Runx3-modulated IFN-γ expression 52 Chapter 1. Introduction 52 1.1 Runx family 52 1.2 Rationale 53 Chapter 2. Experimental Materials 55 2.1 Mice 55 2.2 Vectors 55 Chapter 3. Experimental Methods 56 3.1 Western blotting 56 3.2 Luciferase assay 56 Chapter 4. Results 57 NMTS Domain of Runx3 is the T-bet interacting site to regulate IFN-γcooperatively. 57 Chapter 5. Discussion 59 Figure 60 Figure 11. The Full length NMTS domain of Runx3 control the synergistic effect of T-bet-induced IFN-γ production. 62 References 63 | |
| dc.language.iso | en | |
| dc.subject | 細胞激素 | zh_TW |
| dc.subject | c-Maf | en |
| dc.title | 探討在第十七型輔助性T細胞中SUMO化與酪胺酸磷酸化之c-Maf對於細胞激素基因的結合機轉 | zh_TW |
| dc.title | Recruitment of SUMOylated and tyrosine-phospholated c-Maf to c-Maf mediated cytokine genes in Th17 cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 司徒惠康,伍安怡 | |
| dc.subject.keyword | 細胞激素, | zh_TW |
| dc.subject.keyword | c-Maf, | en |
| dc.relation.page | 68 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-08 | |
| 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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