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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳宏文 | |
dc.contributor.author | Fang-Yu Lin | en |
dc.contributor.author | 林芳宇 | zh_TW |
dc.date.accessioned | 2021-06-15T01:15:43Z | - |
dc.date.available | 2019-07-27 | |
dc.date.copyright | 2009-07-31 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-28 | |
dc.identifier.citation | Baczyk, D., Drewlo, S., Proctor, L., Dunk, C., Lye, S., and Kingdom, J. (2009). Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast. Cell Death Differ 16, 719-727.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42536 | - |
dc.description.abstract | GCM1為於胎盤內特殊表現的轉錄因子,其可調控syncytin膜蛋白的表現,而促進融合滋養層細胞的形成與分化,以維持胎盤構造進行物質交換的重要功能。於細胞內,GCM1活性的調控,可藉由不同層面轉譯後的修飾作用,影響其磷酸化、汎素化及乙烯化的作用程度,而維持GCM1的穩定性和轉錄活性。新近研究已知,當細胞受特定環境刺激,例如:處於缺氧情況下,而活化GSK-3β時,將促進GSK-3β對GCM1上Ser322位置的胺基酸進行磷酸化,促使GCM1與F-box protein FBW2結合,提高被汎素化的程度,而經由26S proteasome進行降解。
於此篇研究中進一步發現,除了對GCM1進行磷酸化作用,細胞中亦存在一特殊的dual-specificity protein phosphatases磷酸水解酶—GIP1,可藉由與GCM1的交互作用,對GCM1進行去磷酸化反應,以逆向調控Ser322位置的磷酸化程度,藉此而降低GCM1被汎素標定的現象,延緩於細胞中被降解的速率,而相對提高其穩定性和轉錄活性。因此,於胎盤發育的過程中,藉由GSK-3β與GIP1對GCM1磷酸化程度的交互調控,將可維持細胞中GCM1一定的穩定度和表現量,以適時促進融合滋養層的分化與發育,維持胎盤功能及構造上的完整。 | zh_TW |
dc.description.abstract | Human GCM1 (Glial cell missing homolog 1) is a placenta-specific transcription factor, which regulates expression of syncytin, a fusogenic membrane protein, and controls the formation of syncytiotrophoblast layer essential for nutrient and gas exchange. In previous studies, we have demonstrated that GCM1 activity can be regulated by different post-translational modifications, including phosphoryaltion, ubiquitination, sumoylation and acetylation. Very recently, it has further been demonstrated that activation of GSK-3β by hypoxia leads to GCM1 phosphorylation on Ser322, which in turn recruits the F-box protein FBW2 to trigger GCM1 ubiquitination and degradation.
In this report, we further identify a dual-specificity protein phosphatase termed GIP1 (GCM1-interacting protein 1), which regulates GCM1 dephosphorylation on Ser322 leading to reduction in GCM1 ubiquitination, and therefore increase in GCM1 stability and transcriptional activity. Together with our previous findings, GCM1 protein stability is reciprocally regulated by GSK-3β and GIP1, which may be critical for regulation of trophoblastic fusion and differentiation of syncytiotrophoblast layer. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T01:15:43Z (GMT). No. of bitstreams: 1 ntu-98-R96b46003-1.pdf: 1114928 bytes, checksum: ad71474a9d1248630b449c214c6c8480 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 目 錄 ……………………………………………………………………I
中文摘要………………………………………………………………III 英文摘要 ………………………………………………………………IV 第一章 緒論 1.1 胎盤…………………………………………………………………1 1.2 人類內生性反轉錄病毒……………………………………………2 1.3 gcm 轉錄因子………………………………………………………4 1.4 磷酸水解酶…………………………………………………………6 1.5 研究動機……………………………………………………………9 第二章 材料及方法 2.1 重組質體的構築……………………………………………………10 2.2 重組蛋白在人類細胞的表現………………………………………14 2.3 共同免疫沉澱法……………………………………………………18 2.4 Luciferase螢光報告基因活性檢測………………………………18 2.5 活體內汎素化作用分析……………………………………………19 2.6 Cycloheximide-chase assay ……………………………………19 2.7 活體外交互作用分析………………………………………………19 2.8 活體外磷酸化及去磷酸化分析……………………………………21 第三章 實驗結果 3.1 GIP1和GCM1轉錄因子的交互作用…………………………………23 3.2 GIP1對GCM1蛋白穩定度的影響……………………………………24 3.3 GIP1對細胞內GCM1汎素化的影響…………………………………25 3.4 GIP1對細胞內GCM1降解速率的影響………………………………26 3.5 GCM1和GIP1進行交互作用的片段…………………………………26 3.6 活體外GIP1對GCM1的去磷酸化作用………………………………27 3.7 GIP1對細胞內GCM1的去磷酸化作用………………………………28 3.8 GIP1對GCM1生理作用的分析………………………………………29 第四章 討論與總結 ……………………………………………………30 第五章 圖表 ……………………………………………………………33 第六章 參考文獻……………………………………………………… 42 | |
dc.language.iso | zh-TW | |
dc.title | 探討蛋白質去磷酸化作用對GCM1蛋白穩定性的調控 | zh_TW |
dc.title | Regulation of GCM1 Stability by Protein Dephosphorylation | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳瑞華,張震東,李明亭,張功耀 | |
dc.subject.keyword | GCM1,DUSP,蛋白質去磷酸化作用,穩定度, | zh_TW |
dc.subject.keyword | GCM1,DUSP,Protein dephosphorylation,stability, | en |
dc.relation.page | 46 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-07-28 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科學研究所 | zh_TW |
顯示於系所單位: | 生化科學研究所 |
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