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標題: | BCAS2在果蠅翅膀發育的功能 BCAS2 Role in Drosophila Wing Development |
作者: | Chia-I Lee 李佳怡 |
指導教授: | 陳小梨(Show-Li Chen) |
關鍵字: | BCAS2,果蠅,發育, BCAS2,Drosophila,development, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | BCAS2 (Breast cancer amplified sequence 2) 為一核蛋白質,在先前研究指出BCAS2可做為雌激素受體在調控基因表現時的輔助因子。本實驗室發現BCAS2可以直接與抑癌蛋白質p53結合,調控p53的基因轉錄活性與p53蛋白質的穩定性。在p53表現正常的細胞株中默化BCAS2會造成細胞凋亡,而在p53表現異常的細胞株中默化BCAS2則會造成細胞生長遲緩,顯示BCAS2可能是細胞正常生長必須的蛋白質。我們實驗室的研究亦指出BCAS2是參與核醣核酸剪切次體Prp19p/CDC5L splicing complex的核心成員之一。且增加BCAS2蛋白質的表現可以增加核醣核酸剪輯的效率。此外,我們也發現BCAS2的C端具有兩個coiled-coil domain是核醣核酸剪輯的功能性區段,而相反的,BCAS2的N端則無法有助於核醣核酸剪輯的進行。因此我的研究是利用果蠅系統發現BCAS2的發育功能。
我們發現降低果蠅體內BCAS2相似蛋白質CG4980的表現會造成果蠅無法發育為成蟲,顯示CG4980為果蠅發育的必須蛋白質。此外,雖然BCAS2與CG4980只有約59%的胺基酸序列相似度,但是BCAS2的表現可以回復默化CG4980所造成的損傷,顯示BCAS2可能在果蠅體內執行與CG4980相似的功能。然而無論是表現BCAS2 N端或是BCAS2 C端的蛋白質區段都無法完全回復默化CG4980所造成的損害,顯示在生物體中,BCAS2的N端及C端都具有重要性,必須同時存在才能執行完整功能。 Breast Cancer Amplified Sequence 2(BCAS2) is a 26 kDa nuclear protein, which was recently reported as a transcriptional cofactor that enhances estrogen receptor–mediated gene expression. Our lab data shows that BCAS2 can stabilize AR and enhance AR transcriptional activity. We also found that depletion of BCAS2 cause apoptosis in p53 wild-type cell lines and cause growth arrest in p53-null cell lines. It has been reported that BCAS2 is one of the Prp19p/CDC5L splicing complex member. We have provide evidence that BCAS2 can regulate constitutive splicing and alternative splicing. Previous study in our lab investigated that BCAS2 C-terminal domain was a functional domain in pre-mRNA splicing, on the other hand, BCAS2 N-terminal domain acted as a dominant negative domain refers to pre-mRNA splicing. In Drosophila, BCAS2 is an essential gene since we knockdown dBCAS2 ubiquitously cause lethality. Moreover, human BCAS2 (hBCAS2) can rescue the damage phenotype caused by knockdown of Drosophila BCAS2 (dBCAS2) on wings. However, neither hBCAS2 C-terminal domain nor hBCAS2 N-terminal domain can compensate for the damage phenotype caused by knockdown of Drosophila BCAS2 (dBCAS2) on wings. These results indicate that in Drosophila, both two domains of BCAS2 are important for Drosophila development. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31907 |
全文授權: | 有償授權 |
顯示於系所單位: | 微生物學科所 |
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