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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊性芳(Hsin-Fang Yang-Yen) | |
| dc.contributor.author | Kuang-Hung Lin | en |
| dc.contributor.author | 林冠宏 | zh_TW |
| dc.date.accessioned | 2021-06-16T08:13:10Z | - |
| dc.date.available | 2019-02-25 | |
| dc.date.copyright | 2014-02-25 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-02-14 | |
| dc.identifier.citation | References
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58380 | - |
| dc.description.abstract | 中文摘要
TCTP在許多真核生物中具有高度保守性，生化研究顯示TCTP是一個鈣結合蛋白且會和很多調控細胞生長或死亡的蛋白交互作用。因為TCTP在T細胞活化會大量表現，所以我們在此篇論文中探討TCTP在T細胞活化時扮演的功能。我們證實了缺乏TCTP時，T細胞活化造成的細胞分裂會嚴重的延遲。更深入的研究發現至少在T細胞裡面，老鼠的TCTP不像果蠅的TCTP一樣是Rheb的GTP交換因子。除此之外，我們發現TCTP和一些轉譯起始複合體內的組成物有物理上的結合，而且在T細胞活化過程中調控很多蛋白的轉譯。有趣的是，缺少TCTP降低了Th1和Th2細胞的分化卻不影響Th17的分化，且反而增加Treg的分化。跟在體外的結果一致， T細胞剔除掉TCTP的老鼠其體內的T細胞反應明顯減弱。綜上所述，我們的研究顯示TCTP調控T細胞的活化很可能是調控了一部分T細胞活化時所需的蛋白的轉譯。 | zh_TW |
| dc.description.abstract | Abstract
Translationally controlled tumour protein (TCTP) is highly conserved among many eukaryotic organisms. Biochemical studies indicate that TCTP is a calcium binding protein that can interact with many proteins implicated in cell growth and death controls. In this study, we investigated the functions of TCTP during T cell activation, since TCTP is markedly up-regulated upon TCR stimulation. We demonstrated that TCTP deficiency significantly delayed the proliferation of T cells following TCR stimulation. Further analysis indicated that, unlike fly TCTP, mouse TCTP did not appear to function as a guanine nucleotide exchange factor (GEF) for Rheb, at least not in T cells. Furthermore, we found that TCTP interacted with some components of the translation initiation complex and regulated translation of a large subset of proteins during T cell activation. Interestingly, deletion of TCTP selectively impaired T cell differentiation into Th1 and Th2 subsets, while exerting no or better effects on Th17 and Treg differentiation, respectively. Consistent with the in vitro differentiation results, mutant mice with specific deletion of TCTP in T cells manifested attenuated immune responses in vivo. All together, our results suggest that TCTP regulates T cell activation and functions likely via modulating protein translation of a subset of proteins required for this process. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T08:13:10Z (GMT). No. of bitstreams: 1 ntu-103-R00448002-1.pdf: 7814362 bytes, checksum: 5ed308623885a97fb7c29b1454aedf81 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | Table of content
List of Figures……………………………………………………………………….ii List of Tables……………………………………………………………………..…iii 中文摘要……..………………………………………………………………………iv Abstract………………………………………………………………………………v 1. Introduction……………………………………………………………………...1 1-1 Translationally controlled tumor protein……………………………………...1 1-2 Roles of mammalian target of rapamycin complex (mTORC) in T cells……..2 1-3 Translation initiation…………………………………………………………..6 2. Materials and Methods…………………………………………………………..9 2-1 Mice………………………………………………………………………...…9 2-2 Flow cytometry analysis……………………………………………………....9 2-3 Immunoblotting………………….……..…………………………………….10 2-4 Real-Time quantitative PCR…………………………………………………11 2-5 Glycolytic flux……………………………………………………………….12 2-6 Immunoprecipitation…………………………………………………………12 2-7 S35-Methionine pulse-labeling assay……………….………………………...13 2-8 Retroviral transduction……………………………………………………….14 2-9 In vitro T cell differentiation………………………………………………....14 2-10 Intracellular staining……………………………………………………...15 2-11 Contact hypersensitive assay…………………………………………..…15 2-12 Immunization and ELISA……………………………………………...…16 2-13 Statistical analysis………………………………………………………...17 3. Results…………………………………………………………………………...18 3-1 TCTP-deficient T cells manifest delayed TCR-mediated proliferation……...18 3-2 TCTP does not regulate mTORC1 activity in activated T cells……………...18 3-3 TCTP is involved in the up-regulated expression of Akt and c-Myc in activated T cells…………………………………………………………………..19 3-4 Overexpression of c-Myc is not sufficient to rescue delayed proliferation of TCTP-KO cells following TCR activation……………………………………….21 3-5 TCTP interacts with some components of the translation machinery and regulates translation of a large subset of proteins during T cell activation………21 3-6 Deletion of TCTP selectively impaired T cell differentiation into the Th1 and Th2, but not the Th17 subsets of helper T cells………………………………….22 3-7 Deletion of TCTP enhanced T cell differentiation into the Foxp3+ regulatory T cells………………………………………………………………………………23 3-8 TCTP-T-KO mice manifested impaired Th1 and Th2 responses in vivo…….23 3-9 TCTP plays a role in T cell-dependent antibody production………………...24 4. Discussion…………………………………………………………..…………….26 5. Figures…………………………………………………………………………….29 6. Table.………………………………………………………………………………53 7. References…………...……………………………………………………………54 | |
| dc.language.iso | en | |
| dc.subject | TCTP | zh_TW |
| dc.subject | T細胞 | zh_TW |
| dc.subject | T cell | en |
| dc.subject | TCTP | en |
| dc.title | 分析TCTP在T細胞中之功能 | zh_TW |
| dc.title | Functional analysis of TCTP in T cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 徐立中(Li-Chung Hsu),黃慶裕(Ching-Yu Huang) | |
| dc.subject.keyword | TCTP,T細胞, | zh_TW |
| dc.subject.keyword | TCTP,T cell, | en |
| dc.relation.page | 58 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-02-14 | |
| 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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