Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20265
標題: 探討人類第四型胜肽精胺酸去亞胺酶之結合蛋白及受質
Identification of the binding proteins and protein substrates for peptidylarginine deiminase 4
作者: 林宥任
Lin, You-Ren
關鍵字: 人類第四型胜肽精胺酸去亞胺酶受質;peptidylarginine deiminase 4;結合蛋白;substrate;binding protein
出版社: 生命科學系所
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摘要: 
人類胜肽精胺酸去亞胺酶 (peptidylarginine deiminase ,PAD) 為鈣離子依賴型蛋白,在轉譯後修飾中將目標蛋白上的arginine轉變為citrulline。而PAD4是PAD家族中唯一具有nuclear localization signal (NLS) 的異構酶,並可入核進行調控。近年來許多研究指出PAD4與許多疾病有關,例如: 類風溼性關節炎 (Rheumatoid arthritis) 和惡性腫瘤。前人文獻指出PAD4與腫瘤抑制因子p53、inhibitor of growth 4 (ING4) 、histone deacetylase 2 (HDAC2) 結合,已知PAD4可將histone、ING4…當作受質 (substrate) 並進行後修飾,但PAD4分別在”結合蛋白”與”受質蛋白”的選擇上並不太清楚,所以我們想要找出在細胞內可能與PAD4結合蛋白或受質蛋白。我們利用大腸桿菌表現純化人類PAD4與PAD4過度表現之細胞HL 60 cell的 lysate進行結合後,經過沖洗與超音波震盪去除雜蛋白後,將樣本進行LC/Q-TOF tandem mass分析,並利用生物資訊的方法進行預測結合蛋白或受質蛋白citrullination的胺基酸 (citrullination site) 。並由MS分析的結果中選擇了C-1-tetrahydrofolate synthase, cytoplasmic、Fatty acid synthase、Catalase、DNA replication licensing factor MCM2、Heat shock protein 75 kDa、Transketolase、Tubulin alpha-1B chain、Tubulin beta chain、Tyrosine-protein phosphatase non-receptor type 6進行基因構築、蛋白純化表現。在我們選用的九個蛋白中的七個已利用RF-cloning的方式將基因構築到表現載體與蛋白表現,並進行PAD4受質測試實驗,其中transketolase、tubulin alpha-1B chain及DNA replication licensing factor MCM2可以當作PAD4的受質可被催化,而在PAD4結合蛋白則是有C-1-tetrahydrofolate synthase與Tubulin alpha-1B chain。
URI: http://hdl.handle.net/11455/20265
其他識別: U0005-2901201315433100
Appears in Collections:生命科學系所

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