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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁博煌(Po-Huang Liang) | |
| dc.contributor.author | Wan-Yu Huang | en |
| dc.contributor.author | 黃婉瑜 | zh_TW |
| dc.date.accessioned | 2022-11-23T09:28:41Z | - |
| dc.date.available | 2021-09-11 | |
| dc.date.available | 2022-11-23T09:28:41Z | - |
| dc.date.copyright | 2021-09-11 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-30 | |
| dc.identifier.citation | 1. Altaf, Reem, et al. 'Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development.' Journal of Biological Research-Thessaloniki 28.1 (2021): 1-15. 2. Salvesen, Guy S., and Vishva M. Dixit. 'Caspases: intracellular signaling by proteolysis.' Cell 91.4 (1997): 443-446. 3. Devarajan, Eswaran, et al. 'Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance.' Oncogene 21.57 (2002): 8843-8851. 4. Lin, Yuan-Feng, et al. 'Targeting the XIAP/caspase-7 complex selectively kills caspase-3–deficient malignancies.' The Journal of clinical investigation 123.9 (2013): 3861-3875. 5. Fulda, Simone, and Domagoj Vucic. 'Targeting IAP proteins for therapeutic intervention in cancer.' Nature reviews Drug discovery 11.2 (2012): 109-124. 6. Schimmer, A. D., et al. 'Targeting XIAP for the treatment of malignancy.' Cell Death Differentiation 13.2 (2006): 179-188. 7. Holcik, Martin, Hilary Gibson, and Robert G. Korneluk. 'XIAP: apoptotic brake and promising therapeutic target.' Apoptosis 6.4 (2001): 253-261. 8. Shiozaki, Eric N., et al. 'Mechanism of XIAP-mediated inhibition of caspase-9.' Molecular cell 11.2 (2003): 519-527. 9. Chai, Jijie, et al. 'Structural basis of caspase-7 inhibition by XIAP.' Cell 104.5 (2001): 769-780. 10. Lu, Miao, et al. 'XIAP induces NF-κB activation via the BIR1/TAB1 interaction and BIR1 dimerization.' Molecular cell 26.5 (2007): 689-702. 11. Vaux, David L., and John Silke. 'IAPs, RINGs and ubiquitylation.' Nature reviews Molecular cell biology 6.4 (2005): 287-297. 12. Huang, Yihua, et al. 'Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain.' Cell 104.5 (2001): 781-790. 13. Stennicke, Henning R., Ciara A. Ryan, and Guy S. Salvesen. 'Reprieval from execution: the molecular basis of caspase inhibition.' Trends in biochemical sciences 27.2 (2002): 94-101. 14. Lamkanfi, Mohamed, and Thirumala-Devi Kanneganti. 'Caspase-7: a protease involved in apoptosis and inflammation.' The international journal of biochemistry cell biology 42.1 (2010): 21-24. 15. Reed, John C. 'Mechanisms of apoptosis.' The American journal of pathology 157.5 (2000): 1415-1430. 16. Srinivasula, Srinivasa M., et al. 'Autoactivation of procaspase-9 by Apaf-1- mediated oligomerization.' Molecular cell 1.7 (1998): 949-957. 17. Reed, John C. 'Mechanisms of apoptosis.' The American journal of pathology 157.5 (2000): 1415-1430. 18. Reed, John C. 'Mechanisms of apoptosis.' The American journal of pathology 157.5 (2000): 1415-1430. 19. Denault, Jean-Bernard, and Guy S. Salvesen. 'Human caspase-7 activity and regulation by its N-terminal peptide.' Journal of Biological Chemistry 278.36 (2003): 34042-34050. 20. Lamkanfi, Mohamed, and Thirumala-Devi Kanneganti. 'Caspase-7: a protease involved in apoptosis and inflammation.' The international journal of biochemistry cell biology 42.1 (2010): 21-24. 21. Inoue, S., et al. 'Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway.' Cell Death Differentiation 16.7 (2009): 1053-1061. 22. Fulda, Simone, and Klaus-Michael Debatin. 'Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy.' Oncogene 25.34 (2006): 4798-4811. 23. Raja Singh, Paulraj, et al. 'Anti‐proliferative and apoptosis inducing effect of nimbolide by altering molecules involved in apoptosis and IGF signalling via PI3K/Akt in prostate cancer (PC‐3) cell line.' Cell biochemistry and function 32.3 (2014): 217-228. 24. Budihardjo, Imawati, et al. 'Biochemical pathways of caspase activation during apoptosis.' Annual review of cell and developmental biology 15.1 (1999): 269-290. 25. Putcha, Girish V., et al. 'Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice.' The Journal of cell biology 157.3 (2002): 441-453. 26. Salvesen, Guy S., and Colin S. Duckett. 'IAP proteins: blocking the road to death's door.' Nature reviews Molecular cell biology 3.6 (2002): 401-410. 27. Yammine, Anthony, Jinlong Gao, and Ann H. Kwan. 'Tryptophan fluorescence quenching assays for measuring protein-ligand binding affinities: principles and a practical guide.' Bio-protocol 9.11 (2019): e3253-e3253. 28. Deveraux, Quinn L., et al. 'Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases.' The EMBO journal 18.19 (1999): 5242-5251. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80147 | - |
| dc.description.abstract | X-linked inhibitor of apoptosis (XIAP) 抑制caspase-3 (CASP3)、7 (CASP7) 和 9，進而阻止細胞凋亡。已在化療抗性癌細胞中發現 XIAP 有過表達的現象。因此，已經開發了幾種小分子的 XIAP 拮抗劑和 SMAC 的模擬物來抑制 XIAP 與這些caspase之間的蛋白質相互作用以殺死腫瘤細胞。XIAP 利用第二個重複 (BIR2) 結構域和 BIR1 和 BIR2 之間的linker來結合並抑制內在凋亡途徑中的 CASP3/7。由這些化合物對缺乏 XIAP:CASP3 和XIAP:CASP7 之間的選擇性，其中一些化合物可能對細胞有毒性。我們之前報導了一種策略，通過選擇性結合CASP7 來破壞 XIAP:CASP7 複合物而不是 XIAP:CASP3，因此該化合物殺死了由化學療法引起的 CASP3 表現量低的 (CASP3/DR) 癌細胞，這些癌細胞中會累積很多 XIAP:CASP7。Shih-Hsun Chen 博士通過電腦模擬鑑定出可逆抑制劑與 CASP7 結合，釋放 XIAP 的linker-BIR2 結構域，並活化 CASP7 以殺死 CASP3/DR 癌細胞（Chen et al.，未發表）。因此，本篇論文旨在表達和純化全長 XIAP，以確認該化合物可以破壞全長 XIAP 和 CASP7 之間的相互作用。我通過使用 CASP7 活性測定、螢光猝滅試驗和 BIAcore 實驗證明了該化合物可以破壞全長 XIAP 與 CASP7 的相互作用。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T09:28:41Z (GMT). No. of bitstreams: 1 U0001-3006202115354900.pdf: 2460142 bytes, checksum: 76a4012522c2cfd3db87e08ce24bb514 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員會審定書 ..i 致謝 ..ii 中文摘要 ..v ABSTRACT ..vi ABBREVIATIONS ..viii (1) INTRODUCTION ..1 1.1 Breast cancer ..1 1.2 Chemoresistance in breast cancer ..1 1.3 XIAP ..2 1.4 Caspase-7 ..4 1.5 Apoptosis ..6 (2) MATERIALS AND METHODS ..9 2.1 Chemicals ..9 2.2 Protein constructs and purification ..9 2.3 Determination of caspase activities ..13 2.4 SEC-MALS (size exclusion chromatography-coupled multiangle light scattering) ..13 2.5 Fluorescence quenching assay ..14 2.6 Protein-protein and protein-compound interaction ..14 (3) RESULTS 3.1 Expression and purification of proteins in E.coli ..16 3.2 Protein-protein and protein-compound interaction ..18 3.3 The activity of caspases was not affected by the compound ..18 3.4 Caspase activity was inhibited by XIAP ..19 3.5 Caspase activity was rescued by the compound ..19 3.6 The interaction between XIAP:CASP7 with the compound was measured by BIAcore ..20 (4) DISCUSSIONS ..22 (5) REFERENCE ..27 (6) FIGURE ..31 | |
| dc.language.iso | en | |
| dc.subject | 癌細胞 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 抗藥性 | zh_TW |
| dc.subject | 小分子藥物 | zh_TW |
| dc.subject | apoptosis | en |
| dc.subject | cancer cell | en |
| dc.subject | Small molecule drugs | en |
| dc.subject | Drug resistance | en |
| dc.title | 表達純化全長 XIAP來檢測 XIAP:CASP7 的可逆抑制劑 | zh_TW |
| dc.title | Expression and purification of the full-length XIAP for confirming a reversible XIAP:CASP7 inhibitor | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 何孟樵(Hsin-Tsai Liu),林源峰(Chih-Yang Tseng) | |
| dc.subject.keyword | 細胞凋亡,抗藥性,小分子藥物,癌細胞, | zh_TW |
| dc.subject.keyword | apoptosis,Drug resistance,Small molecule drugs,cancer cell, | en |
| dc.relation.page | 46 | |
| dc.identifier.doi | 10.6342/NTU202101214 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-31 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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