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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/17644

Title: YY1及DJ-1過量表現之基因轉殖斑馬魚在肝臟發育之研究
Transgenic study of zebrafish liver development by overexpressing YY1 and DJ-1
Authors: Lun-Kuan Chou
周倫寬
Contributors: NTOU:Institute of Bioscience and Biotechnology
國立臺灣海洋大學:生物科技研究所
Keywords: 斑馬魚;肝臟
YY1;DJ-1;p53
Date: 2006
Issue Date: 2011-07-04
Abstract: YY1及MDM2同為p53的負調控因子,能促進細胞週期穩定運作且使細胞持續生長。YY1主要是會與MDM2-p53形成複合體,藉由中斷p300對p53進行乙醯化作用的功能,抑制p53轉錄活性,同時藉此提升MDM2對p53進行泛素化作用的效率,加速造成p53降解。DJ-1在先前研究中發現其扮演調控有關於神經細胞進行細胞凋亡的各種不同機制角色。DJ-1則是須經由PI3K-PTEN 訊息傳遞途徑,促使PKB磷酸化作用,誘導MDM2被磷酸化作用,並且直接造成p53表現量下降。YY1與DJ-1對p53進行負調控皆須透過MDM2的參與。YY1必須透過 MDM2才能與p53直接作用。 本實驗室已經建立出能專一表現肝臟中的YY1 及DJ-1綠色螢光蛋白之基因轉殖魚系統;目前我們已經利用西方墨點法偵測出GFP-YY1 及GFP-DJ-1融合蛋白,因此證明YY1和DJ-1基因轉殖魚已轉殖成功;之後將偵測在受到YY1或DJ-1調控下影響p53降解程度以及p53對下游基因的轉錄活性。未來期望與其他含有p53的負調控因子之基因轉殖魚做雜交,造成p53的表現量降低,導致抵抗力降低,加上透過化學藥物處理後,造成細胞壓力增加,創造出早期腫瘤容易生成的基因轉殖魚系統,有助於未來醫界研究癌症的動物模式。
YY1 and MDM2 are both negative regulators of p53, they keep cell cycle progression and cell proliferation. YY1 blocks p300-dependent acetylation and stabilization of p53, and it also interacts with MDM2 and promotes the formation of a p53-MDM2 complex, thereby enhancing MDM2-mediated ubiquitination of p53. DJ-1, originally identified as an oncogene . Beside, DJ-1 leads to hyperphosphorylation of PKB and results in phosphrylation of MDM2. Then, phosphorylated MDM2 negatively regulates p53. Both YY1 and DJ-1 negatively regulate p53 expression through MDM2. YY1 must combined with MDM2 and interact with p53 directly. Our laboratory had created the constructs, LF2.8-GFP-YY1-V5 and LF2.8-GFP-DJ-1-V5, that can specific express in the liver of zebrafish, and we detected expression of GFP-YY1 and GFP-DJ-1 fusion proteins by Western Blotting. In hence, successfully building transgenic fish lines. Then, we will demonstrate YY1 and DJ-1 negative regulate p53 exprssion by detecting the level of p53 degradation and expression of p53 downstream target gene. In the future, we will cross these two transgenic fishes with transgenic fishes containing other negative regulatory genes. We hope to generate a new transgenic fish model that can occur tumorgenesis easily by chemicals induction ( 4-NQO, TCHQ ). This experiment will provide an opportunity for therapeutic intervention by revealing novel targets for drug design.
URI: http://ethesys.lib.ntou.edu.tw/cdrfb3/record/#G0M94360050
http://ntour.ntou.edu.tw/ir/handle/987654321/17644
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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