【摘要】：[目的]生長抑制因子基因1(Inhibitor of growth gene 1,ING1)定位于人類染色體13q33-34,是1996年發(fā)現的一個生長抑制基因。其主要生理功能為調節(jié)細胞周期,抑制細胞增殖,參與細胞衰老和凋亡調控,并在維持基因組穩(wěn)定方面發(fā)揮重要作用。p33~(ING1b)是其最主要的編碼蛋白。以往的研究證實多數惡性腫瘤細胞中NG1基因突變率很低;其mRNA轉錄豐度及p33~(ING1b)蛋白表達水平目前各家研究結果不一,尚無定論,但較一致的發(fā)現是膠質瘤細胞中有p33~(ING1b)蛋白的亞細胞定位異常,即從正常情況下定位于胞核變?yōu)槎ㄎ挥诎麧{,這可能是導致膠質瘤發(fā)生、發(fā)展的重要因素。一般情況下細胞漿向細胞核內的蛋白轉運通過Importin α/β蛋白轉運系統實現,Importin α作為適配器既與被運載蛋白的核定位信號肽(Nuclear localization signal;NLS)結合,又與Importin β結合,形成三聯轉運復合物,并通過importin β與核孔復合體(Nuclear-pore complex;NPC)作用,啟動一系列入核轉運機制。然而,生理情況下p33~(ING1b蛋白的入核轉運機制怎樣?是什么原因導致了膠質瘤細胞中p33~(ING1b)蛋白的亞細胞定位異常?均尚不清楚,有必要作深入系統的探討。 為此,本研究以p33~(ING1b)蛋白核定位信號肽(p33~(ING1b)NLS)的功能研究入手,采用一系列分子生物學實驗方法,初步探討了生理情況下p33~(NG1b)NLS在p33~(ING1b)入核轉運過程中的作用。旨在為進一步深入探討p33~(ING1b)蛋白正常入核機制及其在膠質瘤細胞中入核失敗的原因提供重要的線索及有用的研究工具。 [方法]在本研究第一部分,我們首先應用逆轉錄PCR(Reverse transcript
[Abstract]:[objective] the growth suppressor gene 1 (Inhibitor of growth gene 1 (ING1) was located on human chromosome 13q33-34. It was identified as a growth suppressor gene in 1996. Its main physiological functions are to regulate cell cycle, inhibit cell proliferation, participate in the regulation of cell senescence and apoptosis, and play an important role in maintaining genomic stability. P33 ~ (ING1b) is the most important coding protein. Previous studies have confirmed that the mutation rate of NG1 gene is very low in most malignant tumor cells, and its mRNA transcription abundance and the expression level of p33 ~ (ING1b) protein are different. However, it was found that the subcellular localization of p33 ~ (ING1b) protein in glioma cells was abnormal, that is, the localization from nucleus to cytoplasm of glioma cells was normal, which may be an important factor leading to the occurrence and development of glioma. In general, the translocation of proteins from cytoplasm to nucleus is realized by Importin 偽 / 尾 protein transport system. Importin 偽, as an adapter, binds to the nuclear localization signal peptide (Nuclear localization signalling peptide (Nuclear localization signaln NLS) of the carrying protein and binds to Importin 尾 to form a triplex transport complex. A series of nuclear transport mechanisms were initiated by the interaction of importin 尾 with Nuclear-pore complex. However, what is the nuclear transport mechanism of p33 ~ (ING1b) protein under physiological conditions? What causes subcellular localization of p33 ~ (ING1b) protein in glioma cells? All are not clear, it is necessary to make a thorough and systematic discussion. Therefore, the function of p33 ~ (ING1b) nuclear localization signal peptide (p33 ~ (ING1b) NLS) was studied, and a series of molecular biological methods were used to explore the role of p33 ~ (NG1b) NLS in the nuclear transport of p33 ~ (ING1b) under physiological conditions. The aim of this study is to provide important clues and useful tools for further study on the mechanism of p33- (ING1b) normal nucleation and the failure of p33- (ING1b) protein entry in glioma cells. [methods] in the first part of this study, we first applied reverse transcription PCR (Reverse transcript
【學位授予單位】：天津醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R346

【參考文獻】

相關期刊論文 前2條

1 于士柱;李莉;管欣琴;安同嶺;;膠質瘤細胞端粒結合因子與ING1基因表達關系的研究[J];中國神經腫瘤雜志;2004年04期

2 ;Genetic alterations and expression of inhibitor of growth 1 in human sporadic colorectal cancer[J];World Journal of Gastroenterology;2005年39期

相關博士學位論文 前1條

1 馬越;膠質瘤ING1基因缺失突變及其表達影響因素的研究[D];天津醫(yī)科大學;2004年

，

本文編號：2197623