黃立民2006-07-262018-07-112006-07-262018-07-112003http://ntur.lib.ntu.edu.tw//handle/246246/22881Vpr 為愛滋病毒附屬基因產物，由96 個氨基酸組成14kDa 蛋白。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。先前的研究中本實驗室利用酵母菌雙混交系統從「骨髓基 因庫」找到一些與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)。SMN 蛋白廣泛存在各種組織、細胞中，此蛋白突變 時會導致「神經細胞凋亡」。HeLa 細胞表現SMN 蛋白會造成Vpr 分佈位置 變化，令我們推測SMN 會影響Vpr 的生物功能。由細胞週期實驗顯示SMN 似乎會影響Vpr 導致的細胞凋亡作用。關於這兩個蛋白生物功能相關性需更進 一步實驗系統來釐清，未來研究重點將放在這兩個蛋白參與在「細胞凋亡」的 訊息傳遞路徑上。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. With the aid of a panel of Vpr deletion and point 5 mutants, we have determined the domains of Vpr involved in the interaction with HAX-1 or SMN1. Over expressed SMN alter the localization of GFP-Vpr fusion protein within HeLa cells, indicating SMN play unknown role in Vpr biological function. Previously studies show that SMN modulate neuron cell apoptosis, but little is known about SMN1 how to cause the degeneration of motor neuron the developing to spinal muscular atrophy disease (SMA). Other 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 correlation between Vpr and SMN that involved in apoptosis pathway. This article provides guidance for report writing under the Grant of National Science Council beginning from fiscal year 1998.application/pdf233955 bytesapplication/pdfzh-TW國立臺灣大學醫學院小兒科愛滋病毒酵母菌雙混種系統VprHAX-1HIV-1yeast two-hybrid systemSMNreporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/22881/1/912314B002153.pdf