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研究生(外文):Hsin-Yin Chang
論文名稱:探討果蠅基因female sterile (l) homeotic轉譯之蛋白質FSH-S
論文名稱(外文):The study of FSH-S, a protein encoded by Drosophila female sterile (l) homeotic
指導教授(外文):Der-Hwa Huang
外文關鍵詞:Drosophila female sterile (1) homeoticfs(1)h
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果蠅中的基因 female sterile (1) homeotic (fs(1)h) 可產生兩個蛋白質產物,FSH-S 及 FSH-L。由於它們帶有兩個 Bromodoamin (BDI and BDII) 和一個 extra terminal (ET) domain, 屬於 BET 蛋白質家族。 雖然 FSH-S 的序列和 FSH-L N-terminal 端上的序列完全相同,根據實驗室先前的研究發現,這兩個蛋白質的功能並不相同。大量表現 FSH-S 或是 FSH-L ,僅有 FSH-S 會造成果蠅同源基因 (HOX gene) 的異位表現並產生同源異性轉變 (homeotic transformation),使果蠅的觸角芒轉化成果蠅的腳。由此可知此蛋白質FSH-S參與在果蠅同源基因的活化。此外,果蠅體外研究 (In vitro) 發現 FSH-S 帶有如同磷酸激酶 (kinase) 的能力。到目前為止,並無任何針對FSH-S 上不同 domain 帶有何種功能的研究。為了瞭解這些domain和磷酸激酶能力對於 FSH-S 參與在活化果蠅同源基因的的功能上是否重要,因此研究了帶有不同 domain 缺失,預測的ATP-binding motif 缺失及蛋白質磷酸化位置 (phosphorylation site) 缺失的基因轉殖果蠅。本篇研究中發現 FSH-S 的兩個 BD 對於FSH-S 參與在活化果蠅同源基因的功能影響很大,特別是 BDI 。此外 BD 的存在與否並不影響 FSH-S 結合在染色體上能力。另一方面,大量表現的 FSH-S 除了會造成果蠅體節的異常之外,也會影響果蠅腳的形態。更進一步的研究發現,大量表現的 FSH-S會對與腳及觸角芒發育有關的基因 Distal-less (Dll) 表現產生負面的影響。這樣的影響也有可能是大量表現的 FSH-S 造成同源異性轉變及腳缺陷的原因之一。
The Drosophila female sterile (1) homeotic (fs(1)h) gene encodes two isoforms, FSH-S and FSH-L, that constitute the Drosophila members of the BET protein family. They contain two bromodomains (BD) and an extra terminal (ET) domain. Based on previous studies, although the sequence of FSH-S is identical to the half of FSH-L, they act differently. Overexpression of FSH-S, but not FSH-L, can induce ectopic HOX gene expression and shows homeotic transformation of arista converts into leg, indicating that FSH-S is involved in HOX gene activation. Furthermore, In vitro study indicated that FSH-S act as a kinase. However, there is no functional study of the BET domains in FSH-S so far. To determine the importance of these domains and the putative kinase activity, phenotypes of a series of transgenic fly containing different domain, putative ATP-binding motif and phosphorylation site deletions were investigated. Here we show that BDs are critical for the FSH-S, especially BDI. However, BDs are not crucial for the chromosome binding ability of FSH-S. In addition to homeotic transformation, FSH-S overexpression can induce leg defect. Further investigation had found that FSH-S overexpression had a negative impact on the expression of Distal-less (Dll), which is required for the development of leg and antenna. This is probably one of the reasons that lead to homeotic transformation and leg defect.
Chinese Abstract.....2
English Abstract.....3
Material and Method..22
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