Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/97808
標題: 利用生物資訊及資料庫預測GCIP之結構與功能
Bioinformatic prediction and experimental validation of GCIP protein structure and function
作者: 徐彬
Bin Hsu
關鍵字: GCIP;c-MYC;HLH;生物資訊;Discovery Studio;Schrodinger;GCIP;c-MYC;HLH;bioinformation;Discovery Studio;Schrodinger
引用: 1. Ishii, R., et al., Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition. EMBO J, 2012. 31(11): p. 2541-52. 2. Ma, W.B., et al., GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. Journal of Cellular Biochemistry, 2007. 100(6): p. 1376-1386. 3. Finver, S.N., et al., Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered. Proceedings of the National Academy of Sciences, 1988. 85(9): p. 3052. 4. Qu, J.J., X.Y. Qu, and D.Z. Zhou, miR4262 inhibits colon cancer cell proliferation via targeting of GALNT4. Mol Med Rep, 2017. 16(4): p. 3731-3736. 5. Wang, K., et al., miR-4262 Promotes Proliferation and Invasion of Human Breast Cancer Cells Through Directly Targeting KLF6 and KLF15. Oncol Res, 2017. 25(2): p. 277-283. 6. Lu, S., et al., MicroRNA-4262 activates the NF-kappaB and enhances the proliferation of hepatocellular carcinoma cells. Int J Biol Macromol, 2016. 86: p. 43-9. 7. Kumar, D., N. Sharma, and R. Giri, Therapeutic Interventions of Cancers Using Intrinsically Disordered Proteins as Drug Targets: c-Myc as Model System. Vol. 16. 2017.
摘要: 
在現今的癌症研究中,如何阻止細胞的加速生長(proliferation)、轉移(metastasis)的能力,可說是目前癌症療法研究的主流,其中最常使用的除了直接殺死癌細胞,還有利用抑制細胞的的細胞週期(Cell cycle)的進行,使得細胞走向死亡,而不會分裂增多。隨著近年來大數據的建立和電腦技術的進步,生物醫學界漸漸開始在實驗之前,先利用電腦軟體或網路資料庫做了各種分析後,再根據運算結果進行研究,如此不但事半功倍,更可以省下不少時間與金錢。本篇利用資料庫和軟體來分析我們實驗室中所研究的Cyclin-D and Grap2 interacting protein (GCIP)蛋白,GCIP蛋白是一個含有第五型Helix-loop-helix結構的抑癌蛋白,雖然先前已有文獻證實GCIP能夠抑制癌化細胞生長,並且其表現量在癌症細胞中顯著的減少,但至今原因為何卻還無人知曉。我們藉由資料庫的搜索找出GCIP的交互作用蛋白,並且其中GCIP與幾種ubiqutin相關的蛋白有交互作用,這些蛋白或許與GCIP的穩定度有關,值得做後續的研究去證明是否與GCIP的減少有顯著關係。另外我們實驗室之前的研究發現,c-MYC這個致癌蛋白與GCIP有交互作用,而c-MYC結構上與GCIP有其相似之處之外,GCIP的結構使其無法直接結合DNA,然而c-MYC只要有MAX形成二聚體就能夠直接與DNA結合。於是我們利用Discovery Studio和Schrodinger兩套軟體,模擬出GCIP與MYC可能的對接模型,相信這些數據在未來解開GCIP詳細機制上,能有一些貢獻。

In today's cancer research, prevent the ability of cell proliferation and metastasis is the mainstream of current cancer therapy research. Among them, the most commonly used ways are to kill cancer cells directly, and to inhibits cell cycle that make cells apoptosis or autophagy. With the establishment of big data and the advancement of computer technology in recent years, biomedical scientists are usually take various analysis using computer software or network databases in the beginning of their experiment start. This will not only save a lot of time, but also save so much money. In this article, we used databases and software to analysis a protein of our lab's research, Cyclin-D and Grap2 interacting protein (GCIP). The GCIP protein is a tumor suppressor protein containing the fifth type Helix-loop-helix structure, although it has been previously reported that GCIP can inhibit the growth of cancerous cells, and its expression is significantly reduced in cancer cells, but so far no one knows why. We searched for the interaction protein of GCIP by searching the database, and GCIP interacts with several ubiqutin-related proteins. These proteins may be related to the stability of GCIP and are worthy of follow-up studies to demonstrate whether there is a significant relationship with the reduction in GCIP. In addition, our previous laboratory research found that c-MYC, an oncogenic protein that interacts with GCIP. c-MYC is structurally similar to GCIP. However, the structure of GCIP makes it impossible to directly bind DNA, but c-MYC can directly bind to DNA as long as MAX forms a dimer. So we use the two software of Discovery Studio and Schrodinger to simulate the possible docking model of GCIP and MYC. We believe that these data will have some contributions in the future to unlock the detailed mechanism of GCIP.
URI: http://hdl.handle.net/11455/97808
Rights: 不同意授權瀏覽/列印電子全文服務
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