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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77307完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孔繁璐(Fan-Lu Kung) | |
| dc.contributor.author | Chien-Ming Chen | en |
| dc.contributor.author | 陳建銘 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:55:10Z | - |
| dc.date.available | 2021-07-10T21:55:10Z | - |
| dc.date.copyright | 2021-02-25 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-02-01 | |
| dc.identifier.citation | Harding, M. W., Galat, A., Uehling, D. E., and Schreiber, S. L. (1989) A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature 341, 758-760. Galat, A. (2004) A note on clustering the functionally-related paralogues and orthologues of proteins: a case of the FK506-binding proteins (FKBPs). Comput Biol Chem 28, 129-140. Somarelli, J. A., Lee, S. Y., Skolnick, J., and Herrera, R. J. (2008) Structure-based classification of 45 FK506-binding proteins. Proteins 72, 197-208. Tong, M., and Jiang, Y. (2015) FK506-Binding Proteins and Their Diverse Functions. Curr Mol Pharmacol 9, 48-65. Kino, T., Hatanaka, H., Hashimoto, M., Nishiyama, M., Goto, T., Okuhara, M., Kohsaka, M., Aoki, H., and Imanaka, H. (1987) FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo) 40, 1249-1255. Ochiai, T., Nakajima, K., Nagata, M., Suzuki, T., Asano, T., Uematsu, T., Goto, T., Hori, S., Kenmochi, T., Nakagoori, T., and et al. (1987) Effect of a new immunosuppressive agent, FK 506, on heterotopic cardiac allotransplantation in the rat. Transplant Proc 19, 1284-1286. Siekierka, J. J., Hung, S. H., Poe, M., Lin, C. S., and Sigal, N. H. (1989) A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature 341, 755-757. Siekierka, J. J., Wiederrecht, G., Greulich, H., Boulton, D., Hung, S. H., Cryan, J., Hodges, P. J., and Sigal, N. H. (1990) The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. J Biol Chem 265, 21011-21015. Markus, P. M., Cai, X., Ming, W., Demetris, A. J., Fung, J. J., and Starzl, T. E. (1991) Prevention of graft-versus-host disease following allogeneic bone marrow transplantation in rats using FK506. Transplantation 52, 590-594. Fruman, D. A., Wood, M. A., Gjertson, C. K., Katz, H. R., Burakoff, S. J., and Bierer, B. E. (1995) FK506 binding protein 12 mediates sensitivity to both FK506 and rapamycin in murine mast cells. Eur J Immunol 25, 563-571. Griffith, J. P., Kim, J. L., Kim, E. E., Sintchak, M. D., Thomson, J. A., Fitzgibbon, M. J., Fleming, M. A., Caron, P. R., Hsiao, K., and Navia, M. A. (1995) X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell 82, 507-522. Kissinger, C. R., Parge, H. E., Knighton, D. R., Lewis, C. T., Pelletier, L. A., Tempczyk, A., Kalish, V. J., Tucker, K. D., Showalter, R. E., Moomaw, E. W., and et al. (1995) Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature 378, 641-644. Aldape, R. A., Futer, O., DeCenzo, M. T., Jarrett, B. P., Murcko, M. A., and Livingston, D. J. (1992) Charged surface residues of FKBP12 participate in formation of the FKBP12-FK506-calcineurin complex. J Biol Chem 267, 16029-16032. Van Duyne, G. D., Standaert, R. F., Karplus, P. A., Schreiber, S. L., and Clardy, J. (1993) Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin. J Mol Biol 229, 105-124. Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., and Abraham, R. T. (1995) Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem 270, 815-822. Choi, J., Chen, J., Schreiber, S. L., and Clardy, J. (1996) Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 273, 239-242. Hausch, F., Kozany, C., Theodoropoulou, M., and Fabian, A. K. (2013) FKBPs and the Akt/mTOR pathway. Cell Cycle 12, 2366-2370. Vilella-Bach, M., Nuzzi, P., Fang, Y., and Chen, J. (1999) The FKBP12-rapamycin-binding domain is required for FKBP12-rapamycin-associated protein kinase activity and G1 progression. J Biol Chem 274, 4266-4272. Chen, Y. G., Liu, F., and Massague, J. (1997) Mechanism of TGFbeta receptor inhibition by FKBP12. EMBO J 16, 3866-3876. Wang, T., Donahoe, P. K., and Zervos, A. S. (1994) Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science 265, 674-676. Huse, M., Chen, Y. G., Massague, J., and Kuriyan, J. (1999) Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12. Cell 96, 425-436. Jayaraman, T., Brillantes, A. M., Timerman, A. P., Fleischer, S., Erdjument-Bromage, H., Tempst, P., and Marks, A. R. (1992) FK506 binding protein associated with the calcium release channel (ryanodine receptor). J Biol Chem 267, 9474-9477. Brillantes, A. B., Ondrias, K., Scott, A., Kobrinsky, E., Ondriasova, E., Moschella, M. C., Jayaraman, T., Landers, M., Ehrlich, B. E., and Marks, A. R. (1994) Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell 77, 513-523. Samso, M., Shen, X., and Allen, P. D. (2006) Structural characterization of the RyR1-FKBP12 interaction. J Mol Biol 356, 917-927. Timerman, A. P., Ogunbumni, E., Freund, E., Wiederrecht, G., Marks, A. R., and Fleischer, S. (1993) The calcium release channel of sarcoplasmic reticulum is modulated by FK-506-binding protein. Dissociation and reconstitution of FKBP-12 to the calcium release channel of skeletal muscle sarcoplasmic reticulum. J Biol Chem 268, 22992-22999. Lyons, W. E., Steiner, J. P., Snyder, S. H., and Dawson, T. M. (1995) Neuronal regeneration enhances the expression of the immunophilin FKBP-12. J Neurosci 15, 2985-2994. Hoeffer, C. A., Tang, W., Wong, H., Santillan, A., Patterson, R. J., Martinez, L. A., Tejada-Simon, M. V., Paylor, R., Hamilton, S. L., and Klann, E. (2008) Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron 60, 832-845. Sugata, H., Matsuo, K., Nakagawa, T., Takahashi, M., Mukai, H., Ono, Y., Maeda, K., Akiyama, H., and Kawamata, T. (2009) A peptidyl-prolyl isomerase, FKBP12, accumulates in Alzheimer neurofibrillary tangles. Neurosci Lett 459, 96-99. Aghdasi, B., Ye, K., Resnick, A., Huang, A., Ha, H. C., Guo, X., Dawson, T. M., Dawson, V. L., and Snyder, S. H. (2001) FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle. Proc Natl Acad Sci U S A 98, 2425-2430. Kang, C. B., Hong, Y., Dhe-Paganon, S., and Yoon, H. S. (2008) FKBP family proteins: immunophilins with versatile biological functions. Neurosignals 16, 318-325. Futer, O., DeCenzo, M. T., Aldape, R. A., and Livingston, D. J. (1995) FK506 binding protein mutational analysis. Defining the surface residue contributions to stability of the calcineurin co-complex. J Biol Chem 270, 18935-18940. DeCenzo, M. T., Park, S. T., Jarrett, B. P., Aldape, R. A., Futer, O., Murcko, M. A., and Livingston, D. J. (1996) FK506-binding protein mutational analysis: defining the active-site residue contributions to catalysis and the stability of ligand complexes. Protein Eng 9, 173-180. Ikura, T., and Ito, N. (2007) Requirements for peptidyl-prolyl isomerization activity: a comprehensive mutational analysis of the substrate-binding cavity of FK506-binding protein 12. Protein Sci 16, 2618-2625. Hopper, J. T., Rawlings, A., Afonso, J. P., Channing, D., Layfield, R., and Oldham, N. J. (2012) Evidence for the preservation of native inter- and intra-molecular hydrogen bonds in the desolvated FK-binding protein.FK506 complex produced by electrospray ionization. J Am Soc Mass Spectrom 23, 1757-1767. Alzheimer, A., Stelzmann, R. A., Schnitzlein, H. N., and Murtagh, F. R. (1995) An English translation of Alzheimer's 1907 paper, 'Uber eine eigenartige Erkankung der Hirnrinde'. Clin Anat 8, 429-431. Wenk, G. L. (2003) Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 64 Suppl 9, 7-10. Williamson, J., and LaRusse, S. (2004) Genetics and genetic counseling: recommendations for Alzheimer's disease, frontotemporal dementia, and Creutzfeldt-Jakob disease. Curr Neurol Neurosci Rep 4, 351-357. Storey, E., and Cappai, R. (1999) The amyloid precursor protein of Alzheimer's disease and the Abeta peptide. Neuropathol Appl Neurobiol 25, 81-97. Goedert, M. (2004) Tau protein and neurodegeneration. Semin Cell Dev Biol 15, 45-49. Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736. Weidemann, A., Konig, G., Bunke, D., Fischer, P., Salbaum, J. M., Masters, C. L., and Beyreuther, K. (1989) Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell 57, 115-126. Ponte, P., Gonzalez-DeWhitt, P., Schilling, J., Miller, J., Hsu, D., Greenberg, B., Davis, K., Wallace, W., Lieberburg, I., and Fuller, F. (1988) A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 331, 525-527. Tanzi, R. E., McClatchey, A. I., Lamperti, E. D., Villa-Komaroff, L., Gusella, J. F., and Neve, R. L. (1988) Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature 331, 528-530. Kitaguchi, N., Takahashi, Y., Tokushima, Y., Shiojiri, S., and Ito, H. (1988) Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331, 530-532. Belyaev, N. D., Kellett, K. A., Beckett, C., Makova, N. Z., Revett, T. J., Nalivaeva, N. N., Hooper, N. M., and Turner, A. J. (2010) The transcriptionally active amyloid precursor protein (APP) intracellular domain is preferentially produced from the 695 isoform of APP in a {beta}-secretase-dependent pathway. J Biol Chem 285, 41443-41454. Haass, C., and Selkoe, D. J. (1993) Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell 75, 1039-1042. Oltersdorf, T., Ward, P. J., Henriksson, T., Beattie, E. C., Neve, R., Lieberburg, I., and Fritz, L. C. (1990) The Alzheimer amyloid precursor protein. Identification of a stable intermediate in the biosynthetic/degradative pathway. J Biol Chem 265, 4492-4497. Georgopoulou, N., McLaughlin, M., McFarlane, I., and Breen, K. C. (2001) The role of post-translational modification in beta-amyloid precursor protein processing. Biochem Soc Symp, 23-36. Lee, M. S., Kao, S. C., Lemere, C. A., Xia, W., Tseng, H. C., Zhou, Y., Neve, R., Ahlijanian, M. K., and Tsai, L. H. (2003) APP processing is regulated by cytoplasmic phosphorylation. J Cell Biol 163, 83-95. Oishi, M., Nairn, A. C., Czernik, A. J., Lim, G. S., Isohara, T., Gandy, S. E., Greengard, P., and Suzuki, T. (1997) The cytoplasmic domain of Alzheimer's amyloid precursor protein is phosphorylated at Thr654, Ser655, and Thr668 in adult rat brain and cultured cells. Mol Med 3, 111-123. Iijima, K., Ando, K., Takeda, S., Satoh, Y., Seki, T., Itohara, S., Greengard, P., Kirino, Y., Nairn, A. C., and Suzuki, T. (2000) Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5. J Neurochem 75, 1085-1091. Ando, K., Oishi, M., Takeda, S., Iijima, K., Isohara, T., Nairn, A. C., Kirino, Y., Greengard, P., and Suzuki, T. (1999) Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation. J Neurosci 19, 4421-4427. Chang, K. A., Kim, H. S., Ha, T. Y., Ha, J. W., Shin, K. Y., Jeong, Y. H., Lee, J. P., Park, C. H., Kim, S., Baik, T. K., and Suh, Y. H. (2006) Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration. Mol Cell Biol 26, 4327-4338. Ramelot, T. A., and Nicholson, L. K. (2001) Phosphorylation-induced structural changes in the amyloid precursor protein cytoplasmic tail detected by NMR. J Mol Biol 307, 871-884. Pastorino, L., Sun, A., Lu, P. J., Zhou, X. Z., Balastik, M., Finn, G., Wulf, G., Lim, J., Li, S. H., Li, X., Xia, W., Nicholson, L. K., and Lu, K. P. (2006) The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440, 528-534. Liu, F. L., Liu, P. H., Shao, H. W., and Kung, F. L. (2006) The intracellular domain of amyloid precursor protein interacts with FKBP12. Biochem Biophys Res Commun 350, 472-477. Liu, F. L., Liu, T. Y., and Kung, F. L. (2014) FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines. J Biosci 39, 85-95. Wu, Y., Li, Q., and Chen, X. Z. (2007) Detecting protein-protein interactions by Far western blotting. Nat Protoc 2, 3278-3284. Huang, T. H.-Y. (2017) Elucidationof the Effects of FKBP12 on APP Processing. Master Thesis, National Taiwan University. Wilson, K. P., Yamashita, M. M., Sintchak, M. D., Rotstein, S. H., Murcko, M. A., Boger, J., Thomson, J. A., Fitzgibbon, M. J., Black, J. R., and Navia, M. A. (1995) Comparative X-ray structures of the major binding protein for the immunosuppressant FK506 (tacrolimus) in unliganded form and in complex with FK506 and rapamycin. Acta Crystallogr D Biol Crystallogr 51, 511-521. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77307 | - |
| dc.description.abstract | FK506-binding protein 12 (FKBP12)為一個能各別與FK506及rapamycin鍵結並形成複合體，且抑制下游phosphatase活性，進而影響T細胞活化、細胞生長甚至蛋白質生合成的蛋白質。而FKBP12本身具有peptidyl-prolyl cis-trans isomerase (PPIase)的酵素活性，可以將蛋白質中位於特定胺基酸proline前的胜肽鍵進行cis/trans轉變，進而改變與其他蛋白質之間的交互作用，而影響此蛋白質走向不同的路徑。本實驗室曾利用酵母菌雙雜交法以及免疫共沉澱法確認FKBP12與APP intracellular domain (AICD)有一定程度的交互作用，且發現當在HEK293T細胞株過量表現FKBP12時，C99/C83比例有上升的趨勢，意即有較多APP以amyloidogenic pathway代謝，而此現象在加入FK506之後會被反轉回來。由先前的FKBP12結構研究中已知FKBP12的Asp37、Arg42、Phe46、Trp59、Tyr82等殘基位於FKBP12與FK506的結合位置，本研究企圖利用一系列在這些位置突變的FKBP12 (FKBP12D37V、FKBP12R42I、FKBP12F46L、FKBP12W59A、FKBP12W59L、FKBP12Y82F)來鑑別對APP-FKBP12交互作用重要的位點，計劃將不同的FKBP12各別與wile-type APP混合，利用免疫共沉澱法觀察其交互作用的差異。 已知免疫共沉澱實驗會受到許多因素影響，例如: detergent、還原劑的種類及濃度、以及溶液的pH值等等，又由於FKBP12與APP可能為酵素與受質之關係，兩者之間的交互作用可能極為短暫，因此在實驗進行過程中，將研究方向轉為克服前述困難之方法開發。此研究結果將可作為未來執行免疫共沉澱實驗鑑別對APP-FKBP12 interaction重要的位點時選擇條件之依據。另外，我們也初步嘗試使用遠西方墨點法，或可作為未來進行APP-FKBP12交互作用研究之輔助方法。 | zh_TW |
| dc.description.abstract | FK506-binding protein 12 (FKBP12) is a protein capable of forming complex with FK506 or rapamycin, leading to the inhibition of downstream phosphatase activity, thus affecting T cell activation, cell growth and protein biosynthesis. FKBP12 has peptidyl-prolyl cis-trans isomerase (PPIase) activity. PPIase can accelerate the cis and trans isomerization of the Xaa-Pro peptide bond, thus changing the interaction with other proteins and may lead these proteins toward different pathways. Our previous study indicated FKBP12 can interact with APP intracellular domain (AICD) by using yeast-two-hybrid and co-immunoprecipitation (co-IP) methods. The C99/C83 ratio has been found to be increased when overexpressing FKBP12 in HEK293T cell line, suggesting a shift in APP processing to the amyloidogenic pathway, but this phenomenon was reverted when adding FK506. It’s known that Asp37, Arg42, Phe46, Trp59 and Tyr82 are at the FK506 binding site of FKBP12 from previous FKBP12 structural study. In this study, we intend to use co-IP method to identify amino acid residues of FKBP12 critical for APP-FKBP12 interaction by using a series of FKBP12 mutants with missense mutations in these amino acid residues (FKBP12D37V, FKBP12R42I, FKBP12F46L, FKBP12W59A, FKBP12W59L and FKBP12Y82F). Co-IP experiment is known to be affected by many factors such as the type and concentrations of detergents and reducing agents present and the pH of the solution, etc. In addition, the interaction between APP and FKBP12 could be too transient to be detected by co-IP as APP may be a substrate of FKBP12 enzyme. The focus of this research, as a result, has shifted to method development during the course of study. Our results could serve to guide future co-IP assays to investigate the interaction between APP and FKBP12. We have also explored the possibilities of using far Western blotting method as a supportive approach for studying APP-FKBP12 interaction in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:55:10Z (GMT). No. of bitstreams: 1 U0001-2501202123410400.pdf: 2926570 bytes, checksum: c902663f69049e1b11f025eb84229510 (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 III 英文摘要 IV 英文縮寫表 VI 目錄 VIII 序論 1 實驗目的 6 實驗材料與方法 7 實驗結果與討論 13 圖表 19 參考文獻 37 附錄 43 | |
| dc.language.iso | zh-TW | |
| dc.subject | 遠西方墨點法 | zh_TW |
| dc.subject | 阿茲海默症 | zh_TW |
| dc.subject | 類澱粉前驅蛋白質 | zh_TW |
| dc.subject | FK506-binding protein 12 (FKBP12) | zh_TW |
| dc.subject | 免疫共沉澱法 | zh_TW |
| dc.subject | Alzheimer’s disease (AD) | en |
| dc.subject | amyloid precursor protein (APP) | en |
| dc.subject | FK506-binding protein 12 (FKBP12) | en |
| dc.subject | co-immunoprecipitation (Co-IP) | en |
| dc.subject | Far Western blot | en |
| dc.title | 鑑別FKBP12與APP交互作用的關鍵胺基酸位點之方法開發 | zh_TW |
| dc.title | Method Development for the Identification of the Amino Acid Residues of FKBP12 Critical for APP-FKBP12 Interaction | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 109-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許麗卿(Lih-Ching Hsu),忻凌偉(Ling -Wei Hsin) | |
| dc.subject.keyword | 阿茲海默症,類澱粉前驅蛋白質,FK506-binding protein 12 (FKBP12),免疫共沉澱法,遠西方墨點法, | zh_TW |
| dc.subject.keyword | Alzheimer’s disease (AD),amyloid precursor protein (APP),FK506-binding protein 12 (FKBP12),co-immunoprecipitation (Co-IP),Far Western blot, | en |
| dc.relation.page | 45 | |
| dc.identifier.doi | 10.6342/NTU202100167 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2021-02-02 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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