人類hPuf-A/KIAA0020蛋白在結構上具有6個類似Pumilio-RNA結合區域(PUF domain),推測可結合在特定基因的3’UTR位置,進而調控特定基因的轉譯。利用抗hPuf-A的單株抗體進行免疫螢光染色去偵測hPuf-A在細胞內的分佈位置,結果發現hPuf-A主要位於細胞核仁內,只有極少量存在細胞核質,利用Actinomycin D、DRB和camptothecin (分別是RNA聚合酶I、聚合酶II以及Topoisomerase I的抑制劑)處理人類癌細胞後,hPuf-A的分佈位置會從核仁轉移至細胞核質,顯示hPuf-A的位置當DNA損傷或RNA不穩定時會呈現動態的轉變;當我們利用siRNA降解hPuf-A蛋白的表現,缺少hPuf-A蛋白表現的細胞在處理基因毒性藥物camptothecin 和UV 後有明顯死亡,大量表現hPuf-A蛋白的細胞在處理camptothecin 和UV後卻能比對照組有明顯存活的情形,顯示hPuf-A的存在可能與基因毒性壓力的細胞反應有關;利用親和性層析與質譜分析以及免疫沉澱分析發現hPuf-A與PARP-1在同一個複合物中,PARP-1的主要功能是維繫DNA的完整性,當DNA受到損傷時PARP-1會對特定蛋白質進行poly(ADPribosyl)ation的轉譯後修飾,提高DNA修補能力,in vitro實驗發現hPuf-A會抑制PARP-1的poly(ADPribosyl)ation活性,進而影響PARP-1在細胞凋亡時被caspase切割的數量,這些結果顯示hPuf-A在RNA與DNA毒性藥物刺激的壓力反應下扮演了重要的角色。
人類hPuf-A/KIAA0020蛋白在結構上具有6個類似Pumilio-RNA結合區域(PUF domain),推測可結合在特定基因的3’UTR位置,進而調控特定基因的轉譯。利用抗hPuf-A的單株抗體進行免疫螢光染色去偵測hPuf-A在細胞內的分佈位置,結果發現hPuf-A主要位於細胞核仁內,只有極少量存在細胞核質,利用Actinomycin D、DRB和camptothecin (分別是RNA聚合酶I、聚合酶II以及Topoisomerase I的抑制劑)處理人類癌細胞後,hPuf-A的分佈位置會從核仁轉移至細胞核質,顯示hPuf-A的位置當DNA損傷或RNA不穩定時會呈現動態的轉變;當我們利用siRNA降解hPuf-A蛋白的表現,缺少hPuf-A蛋白表現的細胞在處理基因毒性藥物camptothecin 和UV 後有明顯死亡,大量表現hPuf-A蛋白的細胞在處理camptothecin 和UV後卻能比對照組有明顯存活的情形,顯示hPuf-A的存在可能與基因毒性壓力的細胞反應有關;利用親和性層析與質譜分析以及免疫沉澱分析發現hPuf-A與PARP-1在同一個複合物中,PARP-1的主要功能是維繫DNA的完整性,當DNA受到損傷時PARP-1會對特定蛋白質進行poly(ADPribosyl)ation的轉譯後修飾,提高DNA修補能力,in vitro實驗發現hPuf-A會抑制PARP-1的poly(ADPribosyl)ation活性,進而影響PARP-1在細胞凋亡時被caspase切割的數量,這些結果顯示hPuf-A在RNA與DNA毒性藥物刺激的壓力反應下扮演了重要的角色。
經歷
- 2012 – 迄今 副教授, 臺大生化科學所
- 2008 – 迄今 合聘助研究員, 中央研究院生物化學所
- 2008 – 2012 助理教授, 臺大生化科學所
- 2005 – 2008 研究員, 馬偕紀念醫院醫研部
- 1999 – 2004 副研究員, 馬偕紀念醫院醫研部
- 1997 – 1999 Postdoc fellow, Dana-Farber Cancer Institute, Harvard Medical School
學歷
- 1993 – 1997 博士, 動物學研究所, 臺灣大學
- 1992 – 1993 碩士, 動物學研究所, 臺灣大學
- 1985 – 1989 學士, 動物系, 臺灣大學
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- Chan WE, Chuang CK, Yeh SH, Chang MS, Chen SS (2006) Journal of virology 80(7), 3225-37 “Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus.”
- Yang YC, Hsu YT, Wu CC, Chen HT, Chang MS (2006) Biochemical and biophysical research communications 343(2), 428-34 “Silencing of astrin induces the p53-dependent apoptosis by suppression of HPV18 E6 expression and sensitizes cells to paclitaxel treatment in HeLa cells.”
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