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研究生:陳宇凡
研究生(外文):Yu-Van Chen
論文名稱:人類淋巴增強因子之結合蛋白Kiaa0941之研究
論文名稱(外文):Isolation and characterization of a Lef-1-interacting protein Kiaa0941
指導教授:林陽生林棋財
指導教授(外文):Young-Sun Lin
學位類別:碩士
校院名稱:國立臺灣海洋大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:37
中文關鍵詞:人類淋巴增強因子結合蛋白
外文關鍵詞:Lef-1Kiaa0941Rab11-FIP2RBDrepression
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Wnt訊息傳遞在發育過程中扮演重要的調控角色,這條調控路徑若不正常的被啟動,則可能會導致癌症。在Wnt的活化下,細胞內的β-catenin會累積並進入核內與LEF-1/Tcfs形成複合體,其中LEF-1/Tcfs扮演辨識Wnt目標基因的角色,而β-catenin則負責基因的活化;在沒有Wnt的活化下,β-catenin 會經由GSK-3磷酸化後被分解而無法累積,此時LEF-1/Tcfs仍可辨識Wnt目標基因,但會帶來一些轉錄抑制因子以抑制Wnt目標基因。目前的研究已經找到許多轉錄的共同調控因子,可與β-catenin及Tcfs共同調控轉錄現象。早先,在本實驗室中發現一個Lef-1的共同調控因子Kiaa0941。在本篇報告中我們發現Kiaa0941與LEF-1在細胞中作用並有專一性的抑制LEF-1引發的轉譯活性。除此之外,在免疫螢光的實驗中,Kiaa0941與LEF-1皆在細胞核中表現。在GST拉下法中,Kiaa0941 的C端可與LEF-1作用;而當C端被去掉時,所剩下的N端區域就無法抑制LEF-1引發的轉譯活性。我們推測Kiaa0941的C端區域在與LEF-1的交互作用中扮演重要的角色。
Wnt signal play an important role to control numerous developmental process by altering specific gene expression pattern , and defects in the β-catenin-Lef/Tcf pathway are involved in the development of several type of cancer. LEF-1/Tcfs transcription factor mediate a nuclear response to Wnt signals by interacting with β-catenin . Upon Wnt stimulated , β-catenin accumulates and interacts with T cell factor/Lymphocyte enhancer binding factor (Tcfs/Lef-1) to activate target genes .In contraries, Wnt signal inactivation would occurβ-catenin degradation by APC and GSK-3 via phosphorylation , but LEF-1/Tcfs could repress the same target genes with other cofactor . Kiaa0941, a cofactor of Lef-1, was identified previously in our lab .In this report, we found that Kiaa0941 interacts with Lef-1 in vivo and repress specifically Lef-1-driven transcriptional activity . Otherwise ,we observed that Kiaa0941 co-localized with Lef-1 in nucleus . C-terminal of Kiaa0941 interacts with Lef-1 in GST pull-down assay, and N-terminal of Kiaa0941 could not repress Lef-1-driven transcriptional activity . It may suggest that C-terminal region of Kiaa0941 may play an important role to interact with Lef-1 .
Cover……………………………………………………..1.

Abstract…………………………………………………...2

Introduction……………………………………………….3

Material and Method…………………………………….11.

Result…………………………………………………….19.

Discussion………………………………………………..23

Figure…………………………………………………….26

Reference………………………………………………....31
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