https://scholars.lib.ntu.edu.tw/handle/123456789/194432
標題: | 愛滋病毒Vpr 蛋白之功能研究及其與HAX-1 和脊椎肌肉萎縮基因之作用(1/3) | 作者: | 黃立民 | 關鍵字: | 愛滋病毒;酵母菌雙混種系統;Vpr;HAX-1;HIV-1;yeast two - hybrid system | 公開日期: | 2002 | 出版社: | 臺北市:國立臺灣大學醫學院小兒科 | 摘要: | Vpr 為愛滋病毒附屬基因蛋白由96 個 氨基酸所組成。病毒生殖週期中Vpr 執行 的多效性功能包括核換位,細胞週期阻 斷,異位活化,增進病毒複製,與細胞凋 亡。酵母菌雙混種系統是鑑定蛋白與蛋白 作用之利器,本實驗室已成功地利用此系 統尋找到一些會與Vpr 蛋白作用之細胞蛋 白,包括訊息傳遞蛋白HAX-1,脊椎肌肉 萎縮基因蛋白SMN1(survival of motor neuron 1, human spinal muscular atrophy disease gene)。進一步的研究發現在HeLa 細胞株同時表達HAX-1 與Vpr-GFP 螢光標 定蛋白時,N 端與全長的HAX-1 蛋白均有阻 斷Vpr 蛋白核換位(nuclear transport)的能 力;而C 端則不具此阻斷能力(blocking function)。我們假定HAX-1 停滯病毒蛋白於 細胞質之功能(cytoplasmic retention)必 定造成宿主細胞功能的改變繼而影響病毒 感染之致病機轉。關於Vpr 與SMN1 相互作 用的功能意義較難釐清是基於神經蛋白 SMN1 如何誘導運動神經失常 (degeneration of motor neuron)造成肌 肉萎縮(muscular atrophy)仍是待解的謎 題。相關研究指出Vpr 會造成神經細胞的 凋亡(apoptosis),部份研究亦證明SMN1 與抗細胞凋亡的蛋白NAIP(neuronal apoptosis inhibitory protein)及Bcl-2 都有關係,我們未來的研究將進一步探究 SMN1 與Vpr 之間功能聯結的關係。 HIV-1 Vpr, a 96-amino-acid 14-kDa protein, has several important and interesting functions, including nuclear translocation of the pre-integration complex, cell cycle arrest at the G2/M phase, transactivation, enhancement of virus replication, and apoptosis. To understand the role of Vpr in HIV-1 life cycle and pathogenesis, yeast two-hybrid system had been used and cDNA encoding HAX-1 or SMN1 protein was identified. Interaction between Vpr and HAX-1 (or SMN1) was characterized by in vitro protein-protein binding assay. Furthermore, over-expressed HAX-1 or N-terminal of HAX-1 in HeLa cells blocks the nuclear transport of a Vpr-GFP fusion protein while C-terminal of HAX-1 fail to block Vpr-GFP nuclear transport. We hypothesize that cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein interaction with human cytoplasmic protein HAX-1 may cause functional changes in the host cell that affect HIV-1 pathogenesis. It is difficult to evaluate the interaction of Vpr and SMN1 since little is known about SMN1 how to cause the degeneration of motor neuron the developing to spinal muscular atrophy disease. Newly studies find that Vpr induces apoptosis in neuronal cells, and the correlations between SMN1 and antiapoptosis protein, NAIP (neuronal apoptosis inhibitory protein) and Bcl-2, has been proved. In coming project we will try to verify the possible functional mechanism. This article provides guidance for report writing under the Grant of National Science Council beginning from fiscal year 1998. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22869 | 其他識別: | 902314B002160 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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902314B002160.pdf | 269.84 kB | Adobe PDF | 檢視/開啟 |
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