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標題: 肝癌與蛋白質磷酸化關聯性資料庫
DPPHCC: A Database of Protein Phosphorylation in Hepatocellular Carcinoma
作者: 宋美儀
Sung, Mei-I
Contributors: 陳玉婷
基因體暨生物資訊學研究所
關鍵字: 蛋白質磷酸化;基序;蛋白激酶
hepatocellular carcinoma;protein phosphorylation;motif;protein kinase
日期: 2013
Issue Date: 2013-11-19 12:02:48 (UTC+8)
Publisher: 基因體暨生物資訊學研究所
摘要: 肝癌是台灣最常見也是死亡率最高的癌症之一,其生成與發展是由多種代謝與訊息傳遞途徑所共同參與,而蛋白質磷酸化是調控訊息傳遞最主要的一種方式。蛋白質的磷酸化是一種可逆反應,可以利用調控蛋白激酶和蛋白磷酸酶的活性來改變受質蛋白質的磷酸化與生化特性,進而調控生理反應;若能發現特定蛋白質的磷酸化與肝癌發展的關係,將有助於了解肝癌發展的分子機制、肝癌治療的藥物開發並提升肝癌診斷的準確度。為此,本研究整合了肝癌相關基因、磷酸化相關基序與其對應蛋白激酶,以及蛋白質表達等相關資料,分別建構HCC-611資料庫、MKA資料庫以及GOCU資料集,並利用基序 (motif) 的特性將肝癌的特定蛋白質與蛋白激酶進行配對,找出可能對肝癌特定蛋白質進行蛋白質磷酸化作用相對應蛋白激酶的資訊,評估肝癌特定蛋白質與蛋白激酶之間交互作用的可能性,結合蛋白質表達的組織、亞細胞位置和時期等資料,提供肝癌特定蛋白質與磷酸化的關聯性預測資訊,以及利用基因所參與的途徑與肝癌的驗證資訊評估基因作為肝癌標記的可能性分析,並建構DPPHCC網頁平台提供上述的資料給使用者參考。最後,本研究所使用的方法亦可應用於其他疾病或其他的蛋白質後轉譯修飾,有助於進一步探討疾病與蛋白質後轉譯修飾之間的關聯性。
Hepatocellular carcinoma (HCC) is one of the most common cancers with highest mortality in Taiwan. Its development is a complex process combined with various metabolic and signaling pathways and post-translational modification. Protein phosphorylation, a reversible reaction, is one of the major regulations of signal transduction. It can regulate the activity of protein kinases and protein phosphatases to alter the phosphorylation and characteristics of their substrate protein. To find the correlation between phosphorylation of specific protein and the development of HCC will achieve on understanding of the molecular mechanism of HCC development, drug design of HCC treatment and improvement the diagnosis accuracy of HCC. Therefore, this study integrated HCC related genes, phosphorylation related motifs with its corresponding protein kinases, and the protein expression related information to construct HCC-611 database, MKA database and GOCU dataset, respectively. The characteristic of motifs were used for pairing of the HCC-specific protein and protein kinase that can provide the candidates of HCC-specific protein kinases. Considering the possibility of interactions between HCC-specific proteins and protein kinases, we combined the protein expression information of tissues, subcellular localization and expression pattern the cell cycle for further analysis, and evaluated the possibility of HCC maker by using the HCC evidence type analysis of the target gene involved in HCC related pathways. DPPHCC website, available at http://predictor.nchu.edu.tw/DPPHCC, provided all the above information for users. We predicted the method used in this study can be applied to other diseases or other post-translational modifications of proteins, that could be helpful for investigating and discussing on the correlation between diseases and post-translational modifications of mark proteins.
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