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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40308完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 繆希椿 | |
| dc.contributor.author | Meng-Wei Liu | en |
| dc.contributor.author | 劉夢薇 | zh_TW |
| dc.date.accessioned | 2021-06-14T16:44:30Z | - |
| dc.date.available | 2013-09-11 | |
| dc.date.copyright | 2008-09-11 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-31 | |
| dc.identifier.citation | Reference
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40308 | - |
| dc.description.abstract | 轉錄因子c-Maf是調控IL-4基因之特異性轉錄因子，並且在第二型輔助型T細胞(T helper 2 cells)的分化中扮演一個極為重要的角色。在被刺激之後，c-Maf的表現量會在Th2細胞以及巨噬細胞中大大提升，並引發大量的IL-4以及IL-10之表現，抑制IL-12的表達。因此，我們假設c-Maf之所以在不同的細胞中會有不同功能，可能是透過和不同的蛋白質有交互作用所致。
利用酵母菌雙雜交系統，我們實驗室已經篩選出SUMOylation的E2 conjugating enzyme Ubc9，E3 ligase PIAS1，以及蛋白酪氨酸磷酸脢PTPN22可能和c-Maf有交互作用。於是藉由螢光共振能量轉移的方法，再次確認了c-Maf的確跟這三個蛋白質有交互作用。另外一項假設是既然c-Maf可以和SUMOylation以及去磷酸脢等酵素有交互作用，暗示了c-Maf可以被SUMOylation以及磷酸化，而這些轉錄後修飾也許會對於c-Maf的轉譯能力造成影響。因此，藉由螢光酵素實驗，發現c-Maf的SUMOylation以及磷酸化突變種對於IL-10基因啟動子有較差的轉錄能力。 | zh_TW |
| dc.description.abstract | C-Maf is an IL-4-specific transcription factor that plays a vital role in Th2 cells differentiation. Upon stimulation, c-Maf is highly upregulated in Th2 cells as well as macrophages, and induces significant IL-4 and IL-10 expression but downregulates IL-12 expression. Thus, we hypothesized that c-Maf may have different functions through interacting with cell-specific proteins in different types of cells. Using yeast two-hybrid system, our group demonstrated that c-Maf can interact with Ubc9, the SUMOylation-specific E2 conjugating enzyme, PIAS1, the SUMOylation E3 ligase, and protein tyrosine phosphatase non-receptor type22 (PTPN22). Therefore, by Fluorescence Resonance Energy Transfer (FRET) assay, the interaction between c-Maf, Ubc9, c-Maf, PIAS1, and c-Maf, PTPN22 are confirmed. Since c-Maf can interact with SUMOylation enzymes and de-phosphorylation enzyme, which suggests that c-Maf undergoes SUMOylation and phosphorylation, these post-translational modification may affect the transactivity of c-Maf. Thereafter, we found that both c-Maf SUMOylation and phosphorylation mutants have poorer transactivity on IL-10 promoter by luciferase assay. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-14T16:44:30Z (GMT). No. of bitstreams: 1 ntu-97-R95449005-1.pdf: 3083580 bytes, checksum: db5f69c6a6484f332c5787b2c5f1d4db (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 封面 i
論文口試委員審定書 ii Acknowledgement iii 中文摘要 iv Abstract v Table of Contents vi Chapter I Introduction ….…………………………………… 1 I. An overview of T helper cells ...…………………………… 1 1.1 The role of T helper cells in immune system …………… 1 1.2 Th1 cell differentiation …………..……………………… 2 1.3 Th2 cell differentiation …………………………………… 2 II. c-Maf and its function……………………………………… 3 2.1 c-Maf ...…...…...…………………………………………… 3 2.2 The role of c-Maf in Th2 cell differentiation ……...……… 5 2.3 Regulation of c-Maf ……………………………………… 5 III. SUMOylation and its function …………………………… 6 3.1 SUMOylation……………………………………………… 6 3.2 Ubc9 ...…...…...……………………………………………… 8 3.3 PIAS1 ...…...…...…………………………………………… 9 IV. PTPN22 and its function…………………………………… 10 4.1 PTPN22 ...…...…...………………………………………… 10 4.2 Biological functions of PTPN22 …...……………………… 10 V. Rationale & objects ………………………………………… 11 Chapter II Materials & Methods ………………………… 12 Part I. Experiment procedures ……………………………… 12 1.1 Constructions …………………………………………… 12 1.2 Cell culture and transfection ……………………………… 14 1.3 SDS-PAGE and Western Blot …………………………… 14 1.4 Confocal microscopy………………………………………... 14 1.5. Fluorescence Resonance Energy Transfer...……………… 15 1.6. Luciferase assay ...…………………………...…………… 17 Part II. Experimental Materials ……………………………… 18 2.1 Enzymes ……………………………….…………………… 18 2.2 Kits …………….…………………………………………… 18 2.3 Chemicals & Reagents ………….………………………… 18 2.4 Instruments & Software …….…………………………… 21 2.5 Media, Solutions & Buffers …………………….………… 22 Chapter III Results ……………………………….…………… 24 I. Confirmation of protein-protein interaction between c-Maf, Ubc9, PIAS1, and PTPN22 by confocal microscopy………………………….……….……….……….… 24 II. Confirm protein-protein interaction between c-Maf, Ubc9, PIAS1, and PTPN22 by Fluorescence Resonance Energy Transfer (FRET) ……………………………….……………… 24 III. Examination of whether c-Maf can undergo SUMOylation by FRET………….…………………….………. 26 IV. Investigate IL-10 expression regulated by phosphorylated and SUMOylated c-Maf in macrophage by Luciferase Reporter Assay …….…….…………….…………….……… 28 Chapter IV Discussion …………………………………….… 29 I. c-Maf interacts with Ubc9 and PIAS1, which might retain it at the nuclear periphery. …….…….…….…….……….… 29 II. c-Maf can undergo SUMO-1 SUMOylation, and SUMO-modified c-Maf may be located in PML bodies, which can thus preclude its access to active chromatin domains. …….…….…….…….…….…….…….…….….….… 30 III. c-Maf interacts with SUMO4 at nuclear periphery. ………….…….….….…….….…….….…….….… 32 IV. c-Maf interacts with PTPN22 in the nucleus. …….…….…….….…….….…….….…….….…….…. 33 V. SUMOylation and phosphorylation mutants of c-Maf have different transactivity on human IL-10 promoter. …….…….…….….…….…….….….…….….……. 34 Tables ………………………………………………….…………… 36 Figures ………………………………………………….………… 40 Reference …………………………………………………………. 59 Appendix …………………………………………………………. 63 | |
| dc.language.iso | en | |
| dc.subject | c-Maf轉錄因子 | zh_TW |
| dc.subject | c-Maf | en |
| dc.title | 分析和c-Maf有交互作用之蛋白質研究以及c-Maf對IL-10之調控 | zh_TW |
| dc.title | Dissect c-Maf-interacting proteins and regulation of IL-10 by c-Maf | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 賴明宗,李建國 | |
| dc.subject.keyword | c-Maf轉錄因子, | zh_TW |
| dc.subject.keyword | c-Maf, | en |
| dc.relation.page | 97 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-08-01 | |
| 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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