分析TCTP在T細胞中之功能

Functional analysis of TCTP in T cells

林冠宏(Kuang-Hung Lin)

指導教授 ： 楊性芳

國立臺灣大學/醫學院/分子醫學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.10412

摘要

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。

關鍵字

TCTP ； T細胞

並列摘要

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.

並列關鍵字

TCTP ； T cell

參考文獻

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