碩士 / 國立臺灣海洋大學 / 生物科技研究所 / 95 / 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.
| Identifer | oai:union.ndltd.org:TW/095NTOU5111034 |
| Date | January 2007 |
| Creators | Lun-Kuan Chou, 周倫寬 |
| Contributors | Gour-Mour Her, 何國牟 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 68 |
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