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Title: | 針對二候選肝癌基因之功能性研究 Studies on The Function of Two Hepatocellular Carcinoma Candidate Genes--Cyclase-associated Protein 1 and Cofilin |
Authors: | Fa-Han Lee 李法漢 |
Advisor: | 林榮耀 |
Keyword: | 腺核苷,環化脢結合蛋白,肝癌, cofilin,CAP1,cyclase-associated protein 1,HCC, |
Publication Year : | 2005 |
Degree: | 碩士 |
Abstract: | 腺核苷環化酶結合蛋白(cyclase-associated protein)最早是在酵母菌中被發現的一個具有雙重功能的特殊蛋白,其胺基端功能區被發現和腺核苷環化酶/環腺單核苷之訊息傳遞有關,羧基端則具有一肌動球蛋白結合功能區。然而隨著演化的進行,胺基端功能區逐漸失去原有的特性,相對的羧基端功能區則具有高度的保留性。在豬和黏菌的研究則發現CAP能隔絕肌動球蛋白而造成細胞內微絲的瓦解。除了胺基端和羧基端之外,CAP的中間區段則含有兩個多重脯胺酸片段,分別為P1及P2。已知P2片段具有SH3結合能力,而P1片段的功能則屬未知。如此,CAP在高等真核細胞中應和調控微絲的形成有關,但其在細胞生理上的定位,尚不明朗。
本實驗室近年來致力於肝癌相關基因的研究。藉著高速大量的核酸定序分析,我們在一個C型肝炎肝細胞癌(HCV-infected hepatocellular carcinoma)全長cDNA基因庫中發現數個具有缺陷的cDNA,其中包含人類第一型腺核苷環化酶結合蛋白(CAP1)的缺陷突變株。序列比對分析的結果顯示,此一缺陷將造成CAP1第97個甲胺酸到第319個脯胺酸被刪除( Cyclase-associated protein (CAP) was first identified in yeast. Yeast CAP is a special bifunctional protein whose N-terminal domain interacts with the adenylyl cyclase, and C-terminal has a G-actin binding activity and an actin binding domain. In higher eukaryotes, CAP protein loses its ability to interact with adenylyl cyclase, while the actin binding ability is conserved during evolution. Studies in Dictyostelium discoideum and porcine CAP homologs suggested that CAP can act as an actin-squestering factor which causes F-actin depolymerization. Another important functional domain lies within the internal part of CAP, which contains two poly-proline motifs, P1 and P2. The less conserved P2 motif has been proved to be a SH3-binding domain, while the function of the highly conserved P1 motif is still not clear. Previous studies of yeast CAP have shown that the P2 motif is responsible for CAP’s cytoskeletal localization. In brief, CAP and its homologs are believed to regulate actin cytoskeleton, although the actual biological functions of CAP protein have not yet been determined. By high-throughput sequence analysis of a human hepatocellular carcinoma (HCC) full-length cDNA library (constructed from a human hepatitis C virus infected cancer patient’s tumor and normal tissue), a deletion mutant ( |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/39204 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 生物化學暨分子生物學科研究所 |
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