| 摘要: | 泛素為一常見於細胞中的小蛋白質，主要用以標記蛋白質受質，並進行後續如去氧
核醣核酸修復、蛋白質水解等路徑。標記泛素的過程稱謂泛素化，其透過泛素活化酶、 泛素結合酶與泛素連接酶將特定受質接上泛素。其中，泛素連接酶負責辨識特定的受質， 扮演泛素化中的關鍵角色。前信使核糖核酸加工因子 19 為其中一種泛素連接酶，與去 氧核醣核酸修復與信使核糖核酸剪接有所關聯，並被發現在肺癌中有過度表現的現象。 我對大於五千八百種蛋白質的酵母菌蛋白質體晶片進行前信使核糖核酸加工因子 19 的 胞外泛素化實驗，篩選出其對應的四十五個受質，並透過生物資訊的方式找到這四十五 個受質共有結合序列與前信使核糖核酸加工因子 19 透過泛素化受質而進一步產生關聯 的十類生物機制、七類細胞組件、六類分子功能與十二類路徑。另外，在四十五個受質 中，四十個牽涉到七類生物機制、四類細胞組件以及兩類路徑與前信使核糖核酸加工因 子 19 有關聯。此外，有三類生物機制、六類細胞組件和三類分子功能呈現顯著富集。 還有，我找出兩組受質分別有不同的序列模組，提供與前信使核糖核酸加工因子 19 可 能的結合點。根據結果，我找到這些基因本體論與路徑可能透過受質泛素化而被前信使 核糖核酸加工因子 19 所調控，對前信使核糖核酸加工因子 19 進一步的研究方向。;Ubiquitin is a common small protein in cells, it usually served as tag conjugated to the substrate, for DNA repair, proteolysis, and others. This process is called ubiquitination, which ubiquitinates specific substrates by ubiquitin activation enzyme, ubiquitin conjugating enzyme and ubiquitin ligase. Ubiquitin ligase serves as a critical point for substrates specificity. Pre- mRNA-processing factor 19 (PRP19) is one of the ubiquitin ligases, involves in DNA repair, mRNA splicing, and has been found overexpressed in lung cancer. I found forty-five substrates of PRP19 from in vitro ubiquitination assay on yeast proteome chip which contains more than 5800 kinds of the yeast protein. I used bioinformatics analysis to find PRP19 further involving ten classes of biological processes, seven classes of cellular components, six classes of molecule functions, and twelve classes of pathways by ubiquitinates its substrates. Forty of forty-five substrates involved in seven classes of biological processes, four classes of cellular components and two pathways which relate to PRP19.In addition, there were three classes of biological processes, six classes of cellular components, three classes of molecule functions were significantly enriched. Also, I found two groups of substrates had different consensus motifs as putative binding sites with PRP19. According to the result, I found those GO and pathways might be regulated by PRP19-substrates ubiquitination, it gave the direction for
further study on PRP19. |
