請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42536
標題: | 探討蛋白質去磷酸化作用對GCM1蛋白穩定性的調控 Regulation of GCM1 Stability by Protein Dephosphorylation |
作者: | Fang-Yu Lin 林芳宇 |
指導教授: | 陳宏文 |
關鍵字: | GCM1,DUSP,蛋白質去磷酸化作用,穩定度, GCM1,DUSP,Protein dephosphorylation,stability, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42536 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-98-1.pdf 目前未授權公開取用 | 1.09 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。