臺灣博碩士論文加值系統

異質核醣核酸蛋白K (Heterogeneous Nuclear Ribonucleoprotein K, hnRNP K)，異質核醣核酸蛋白粒（hnRNP particles）中的成員，是一個多功能性的蛋白質，已知其功能涉及了基因的轉錄、轉譯、運輸及在細胞內訊號傳遞等層面。在基因表現的層面，hnRNP K依基因表現系統的不同及細胞株的差異而扮演活化與抑制二種不同的角色。近來的研究中顯示，當細胞遭受到DNA損傷時，hnRNP K的蛋白質量會因此增加進而提升p53標的基因的表現量，其功能可視為p53的輔因子。然而hnRNP K在調節p53標的基因的作用機轉以及與p53蛋白間的蛋白質交互作用方面尚不明確。而最近的研究結果也顯示了，hnRNP K的精胺酸會受到PRMT 1（protein arginine methyltransferase 1）而非CARM1（Coactivator-associated arginine methyltransferase 1）的甲基化修飾，而影響hnRNP K與其他蛋白質之間的交互作用，進而改變hnRNP K在轉譯調節上的作用機轉。本論文將探討hnRNP K本身是否具有轉錄活化及其甲基化後是否會造成其作為p53輔因子角色的改變。由實驗結果發現hnRNP K作為一個轉錄活化因子，其胺基酸338-390區域為十分強力的轉錄活化區；而經由PRMT 1甲基化修飾的hnRNP K對其轉錄活性的調控則無顯著的影響。

Heterogeneous nuclear ribonucleoprotein (hnRNP) K, a component of the hnRNP particles, is a multifunctional protein known to be involved in several steps of regulation of transcription, translation, nuclear transport and signal transduction. Involvement of hnRNP K protein in gene expression has been demonstrated, hnRNP K protein can both activate and repress these processes, depending on different cell lines or gene expression system. The current study has showed that hnRNP K would be induced after DNA damage and be a transcription coactivator for regulating the expression of p53-target gene. However, the mechanism of hnRNP K for regulating the expression of p53-target gene remains unclear. Recent studies also show that arginine methylation of hnRNP K by PRMT 1,not CARM 1 would influence the protein-protein interaction and the ability of transcriptional regulation. In this study, we identified the transcriptional activation domain of hnRNP K and demonstrate that no effect of arginine methylation of hnRNP K on its induction of p53-target gene expression, suggesting that the arginine methylation of hnRNP K is not involved in regulating the p53 functions.

目錄………………………………………………………………… Ⅰ
縮寫表……………………………………………………………… Ⅱ
表目錄……………………………………………………………… Ⅲ
圖目錄……………………………………………………………… Ⅳ
中文摘要…………………………………………………………… Ⅴ
英文摘要…………………………………………………………… Ⅵ
第一章：緒論……………………………………………………… 1
第二章：材料與方法………………………………………………. 11
第三章：結果………………………………………………………. 30
第四章：討論………………………………………………………. 38
第五章：參考文獻…………………………………………………. 41
表…………………………………………………………………… 52
圖…………………………………………………………………… 53

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