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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 張世宗(Shih-Chung Chang) | |
dc.contributor.author | Siao-Jing Tang | en |
dc.contributor.author | 唐曉菁 | zh_TW |
dc.date.accessioned | 2021-06-15T05:44:13Z | - |
dc.date.available | 2012-08-20 | |
dc.date.copyright | 2010-08-20 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-19 | |
dc.identifier.citation | Baker, R. T., J. W. Tobias, et al. (1992). 'Ubiquitin-specific proteases of Saccharomyces cerevisiae. Cloning of UBP2 and UBP3, and functional analysis of the UBP gene family.' J Biol Chem 267(32): 23364-23375.
Bohren, K. M., V. Nadkarni, et al. (2004). 'A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.' J Biol Chem 279(26): 27233-27238. Bylebyl, G. R., I. Belichenko, et al. (2003). 'The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast.' J Biol Chem 278(45): 44113-44120. Chan, Y., J. Yoon, et al. (2008). 'DEN1 deneddylates non-cullin proteins in vivo.' J Cell Sci 121(Pt 19): 3218-3223. Chiba, T. and K. Tanaka (2004). 'Cullin-based ubiquitin ligase and its control by NEDD8-conjugating system.' Curr Protein Pept Sci 5(3): 177-184. Ciechanover, A. (2005). 'Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture).' Angew Chem Int Ed Engl 44(37): 5944-5967. Ciechanover, A. (2005). 'Proteolysis: from the lysosome to ubiquitin and the proteasome.' Nat Rev Mol Cell Biol 6(1): 79-87. Ciechanover, A. and R. Ben-Saadon (2004). 'N-terminal ubiquitination: more protein substrates join in.' Trends Cell Biol 14(3): 103-106. Colby, T., A. Matthai, et al. (2006). 'SUMO-conjugating and SUMO-deconjugating enzymes from Arabidopsis.' Plant Physiol 142(1): 318-332. Cope, G. A., G. S. Suh, et al. (2002). 'Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1.' Science 298(5593): 608-611. Desterro, J. M., M. S. Rodriguez, et al. (1998). 'SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.' Mol Cell 2(2): 233-239. Desterro, J. M., J. Thomson, et al. (1997). 'Ubch9 conjugates SUMO but not ubiquitin.' FEBS Lett 417(3): 297-300. Dye, B. T. and B. A. Schulman (2007). 'Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins.' Annu Rev Biophys Biomol Struct 36: 131-150. Falquet, L., N. Paquet, et al. (1995). 'A human de-ubiquitinating enzyme with both isopeptidase and peptidase activities in vitro.' FEBS Lett 359(1): 73-77. Gan-Erdene, T., K. Nagamalleswari, et al. (2003). 'Identification and characterization of DEN1, a deneddylase of the ULP family.' J Biol Chem 278(31): 28892-28900. Goldenberg, S. J., T. C. Cascio, et al. (2004). 'Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases.' Cell 119(4): 517-528. Gong, L. and E. T. Yeh (2006). 'Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3.' J Biol Chem 281(23): 15869-15877. Goodson, M. L., Y. Hong, et al. (2001). 'Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor.' J Biol Chem 276(21): 18513-18518. Haas, A. L. and I. A. Rose (1982). 'The mechanism of ubiquitin activating enzyme. A kinetic and equilibrium analysis.' J Biol Chem 257(17): 10329-10337. Hasselgren, P. O. and J. E. Fischer (1997). 'The ubiquitin-proteasome pathway: review of a novel intracellular mechanism of muscle protein breakdown during sepsis and other catabolic conditions.' Ann Surg 225(3): 307-316. Hershko, A. and A. Ciechanover (1998). 'The ubiquitin system.' Annu Rev Biochem 67: 425-479. Hay, R. T. (2005). 'SUMO: a history of modification.' Mol Cell 18(1): 1-12. Hu, M., P. Li, et al. (2002). 'Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde.' Cell 111(7): 1041-1054. Huang, D. T., D. W. Miller, et al. (2004). 'A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.' Nat Struct Mol Biol 11(10): 927-935. Huang, D. T., H. Walden, et al. (2004). 'Ubiquitin-like protein activation.' Oncogene 23(11): 1958-1971. Johnson, E. S. (2004). 'Protein modification by SUMO.' Annu Rev Biochem 73: 355-382. Johnson, E. S. and G. Blobel (1997). 'Ubc9p is the conjugating enzyme for the ubiquitin-like protein Smt3p.' J Biol Chem 272(43): 26799-26802. Johnson, E. S., I. Schwienhorst, et al. (1997). 'The ubiquitin-like protein Smt3p is activated for conjugation to other proteins by an Aos1p/Uba2p heterodimer.' EMBO J 16(18): 5509-19 Kagey, M. H., T. A. Melhuish, et al. (2005). 'Multiple activities contribute to Pc2 E3 function.' EMBO J 24(1): 108-19. Kerscher, O. (2007). 'SUMO junction-what's your function? New insights through SUMO-interacting motifs.' EMBO Rep 8(6): 550-555. Kerscher, O., R. Felberbaum, et al. (2006). 'Modification of proteins by ubiquitin and ubiquitin-like proteins.' Annu Rev Cell Dev Biol 22: 159-180. Knipscheer, P., W. J. van Dijk, et al. (2007). 'Noncovalent interaction between Ubc9 and SUMO promotes SUMO chain formation.' EMBO J 26(11): 2797-807. Kirsh, O., J. S. Seeler, et al. (2002). 'The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase.' EMBO J 21(11): 2682-91. Koegl, M., T. Hoppe, et al. (1999). 'A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly.' Cell 96(5): 635-644. Kurepa, J., J. M. Walker, et al. (2003). 'The small ubiquitin-like modifier (SUMO) protein modification system in Arabidopsis. Accumulation of SUMO1 and -2 conjugates is increased by stress.' J Biol Chem 278(9): 6862-6872. Lake, M. W., M. M. Wuebbens, et al. (2001). 'Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex.' Nature 414(6861): 325-329. Li, S. J. and M. Hochstrasser (2003). 'The Ulp1 SUMO isopeptidase: distinct domains required for viability, nuclear envelope localization, and substrate specificity.' J Cell Biol 160(7): 1069-1081. Liakopoulos, D., G. Doenges, et al. (1998). 'A novel protein modification pathway related to the ubiquitin system.' EMBO J 17(8): 2208-2214. Long, J., D. Zuo, et al. (2005). 'Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin.' J Biol Chem 280(42): 35477-89. Matic, I., M. van Hagen, et al. (2008). 'In vivo identification of human small ubiquitin-like modifier polymerization sites by high accuracy mass spectrometry and an in vitro to in vivo strategy.' Mol Cell Proteomics 7(1): 132-144. Matunis, M. J., J. Wu, et al. (1998). 'SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex.' J Cell Biol 140(3): 499-509. McCusker, D., M. Wilson, et al. (1999). 'Organization of the genes encoding the human proteasome activators PA28alpha and beta.' Immunogenetics 49(5): 438-445. Merchant, S. S., S. E. Prochnik, et al. (2007). 'The Chlamydomonas genome reveals the evolution of key animal and plant functions.' Science 318(5848): 245-250. Mossessova, E. and C. D. Lima (2000). 'Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast.' Mol Cell 5(5): 865-876. Mukhopadhyay, D., F. Ayaydin, et al. (2006). 'SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.' J Cell Biol 174(7): 939-949. Navarro, M. S. and J. Bachant (2008). 'RanBP2: a tumor suppressor with a new twist on TopoII, SUMO, and centromeres.' Cancer Cell 13(4): 293-295. Ogunjimi, A. A., D. J. Briant, et al. (2005). 'Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.' Mol Cell 19(3): 297-308. Owerbach, D., E. M. McKay, et al. (2005). 'A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation.' Biochem Biophys Res Commun 337(2): 517-520. Pichler, A., A. Gast, et al. (2002). 'The nucleoporin RanBP2 has SUMO1 E3 ligase activity.' Cell 108(1): 109-20. Rabut, G. and M. Peter (2008). 'Function and regulation of protein neddylation. 'Protein modifications: beyond the usual suspects' review series.' EMBO Rep 9(10): 969-976. Reverter, D. and C. D. Lima (2004). 'A basis for SUMO protease specificity provided by analysis of human Senp2 and a Senp2-SUMO complex.' Structure 12(8): 1519-1531. Reverter, D. and C. D. Lima (2005). 'Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex.' Nature 435(7042): 687-692. Reverter, D. and C. D. Lima (2006). 'Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.' Nat Struct Mol Biol 13(12): 1060-1068. Reverter, D., K. Wu, et al. (2005). 'Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1.' J Mol Biol 345(1): 141-151. Reyes-Turcu, F. E., K. H. Ventii, et al. (2009). 'Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.' Annu Rev Biochem 78: 363-397. Saitoh, H., D. B. Sparrow, et al. (1998). 'Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2.' Curr Biol 8(2): 121-4. Sampson, D. A., M. Wang, et al. (2001). 'The small ubiquitin-like modifier-1 (SUMO-1) consensus sequence mediates Ubc9 binding and is essential for SUMO-1 modification.' J Biol Chem 276(24): 21664-9. Schwartz, D. C., R. Felberbaum, et al. (2007). 'The Ulp2 SUMO protease is required for cell division following termination of the DNA damage checkpoint.' Mol Cell Biol 27(19): 6948-6961. Schwienhorst, I., E. S. Johnson, et al. (2000). 'SUMO conjugation and deconjugation.' Mol Gen Genet 263(5): 771-786. Seeler, J. S., O. Bischof, et al. (2007). 'SUMO, the three Rs and cancer.' Curr Top Microbiol Immunol 313: 49-71. Semple, C. A. (2003). 'The comparative proteomics of ubiquitination in mouse.' Genome Res 13(6B): 1389-1394. Shen, L. N., H. Liu, et al. (2005). 'Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1.' EMBO J 24(7): 1341-1351. Spence, J., S. Sadis, et al. (1995). 'A ubiquitin mutant with specific defects in DNA repair and multiubiquitination.' Mol Cell Biol 15(3): 1265-1273. Sun, L. and Z. J. Chen (2004). 'The novel functions of ubiquitination in signaling.' Curr Opin Cell Biol 16(2): 119-126. Tang, Z., C. M. Hecker, et al. (2008). 'Protein interactions in the sumoylation cascade: lessons from X-ray structures.' FEBS J 275(12): 3003-15. Tatham, M. H., E. Jaffray, et al. (2001). 'Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9.' J Biol Chem 276(38): 35368-35374. Thrower, J. S., L. Hoffman, et al. (2000). 'Recognition of the polyubiquitin proteolytic signal.' EMBO J 19(1): 94-102. Tolkatchev, D., S. Malik, et al. (2008). 'Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities.' Protein Sci 17(4): 711-724. Vertegaal, A. C., S. C. Ogg, et al. (2004). 'A proteomic study of SUMO-2 target proteins.' J Biol Chem 279(32): 33791-33798. Vertegaal, A. C. (2007). 'Small ubiquitin-related modifiers in chains.' Biochem Soc Trans 35(Pt 6): 1422-3. Wang, Y., I. Ladunga, et al. (2008). 'The small ubiquitin-like modifier (SUMO) and SUMO-conjugating system of Chlamydomonas reinhardtii.' Genetics 179(1): 177-192. Wotton, D. and J. C. Merrill (2007). 'Pc2 and SUMOylation.' Biochem Soc Trans 35(Pt 6): 1401-4. Wu, K., K. Yamoah, et al. (2003). 'DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1.' J Biol Chem 278(31): 28882-28891. Xirodimas, D. P., M. K. Saville, et al. (2004). 'Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity.' Cell 118(1): 83-97. Xu, Z. and S. W. Au (2005). 'Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1.' Biochem J 386(Pt 2): 325-330. Shine, Y. C., et al. (2010). '.Biochemical characterization of the small ubiquitin-like modifiers of Chlamydomonas reinhardtii ' Planta 232(3):649-62. Zheng, N., B. A. Schulman, et al. (2002). 'Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.' Nature 416(6882): 703-709. Zheng, N., P. Wang, et al. (2000). 'Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases.' Cell 102(4): 533-539. 蔡佳芸 (2009) 胞外SUMO 化系統之建立與多SUMO化機制之探討,碩士論文,國立台灣大學微生物與生化學系 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46965 | - |
dc.description.abstract | 泛素與類泛素蛋白質修飾系統是利用類泛素胜肽酶、E1活化酶、E2銜接酶、甚至是E3黏合酶的作用,才能將這些小分子量的蛋白質修飾分子接至目標蛋白質的Lysine上。對人類、阿拉伯芥及酵母菌之類泛素蛋白質胜肽酶的相關研究,已經有相當多的文獻發表;相較之下,單胞綠藻在此方面的研究則仍未見。
因此,本研究致力於單胞綠藻 (Chlamydomonas reinhardtii) 中類泛素蛋白質胜肽酶的身分鑑定與生化性質分析。利用人類及阿拉伯芥類泛素蛋白質胜肽酶之序列對單胞綠藻資料庫進行搜尋與比對後,以專一性引子成功選殖出具有NEDD8 (neural precursor cell-expressed developmentally down-regulated 8) 專一性蛋白酶活性之蛋白質,並將其命名為C. reinhardtii deneddylase-1 (CrDEN1)。另外,本研究成功從單胞綠藻中選殖出N端為泛素與C端為NEDD8的特殊融合蛋白質C. reinhardtii Bi-ubiquitin (CrBi-Ub)。其能作為去泛素化酵素與NEDD8蛋白酶的受質。進一步利用CrBi-Ub之定位點突變及人類的USP2-core (ubiquitin-specific protease 2 catalytic core)與SENP8 (SUMO-specific protease 8) 來進行泛素與NEDD8蛋白酶酵素專一性的研究,發現第51號與72號之胺基酸對CrDEN1在專一性分辨泛素與NEDD8上扮演重要的角色。除此之外,本實驗所選殖到的Ubl-specific peptidase-279 (CrULP-279) 可能是一種SUMO蛋白酶,而未知其基質專一性的Ubl-specific peptidase-160 (CrULP-160) 則有待進一步的研究。 關鍵字:泛素、SUMO、NEDD8、類泛素蛋白質胜肽酶、SENP、CrBi-Ub | zh_TW |
dc.description.abstract | Ubiquitin and ubiquitin-like protein (Ubl) modification systems, composed of specific peptidases, E1 activating enzymes, E2 conjugating enzymes and E3 ligases, can specifically conjugate ubiquitin and Ubl to the lysine residues of target proteins. Studies of ubiquitin and Ubl-specific peptidases (USPs) in human, Arabidopsis and yeast have been reported in the literatures. However, the ubiquitin and USPs in Chlamydomonas reinhardtii have not been revealed.
This study focuses on the biochemical characterization of USPs of C. reinhardtii. By searching the C. reinhardtii gene bank with the amino acid sequences of human and Arabidopsis USPs, a gene encoding for the NEDD8 (neural precursor cell-expressed developmentally down-regulated 8)-specific peptidase has been identified and named C. reinhardtii deneddylase 1 (CrDEN1). Furthermore, a fusion protein consisting of an N-terminal ubiquitin and a C-terminal NEDD8 in a head-to-tail orientation has also been identified. Based on the sequence observation, this unique bi-ubiquitin protein was named CrBi-Ub, which can be considered as a substrate of deubiquitinating enzyme and NEDD8 protease. By using site-directed mutagenesis on CrBi-Ub and analysis of the proteolytic activities of USP2-core, SENP8 and CrDEN1, our data reveal that position 51 and 72 play crucial roles in molecular determinants of ubiquitin NEDD8 discrimination. Another USP named CrULP-279 in the study performed the activity of SUMO protease, but the CrULP-160 did not show any catalytic activity against the Ubl proteins analyzed in the experiments. The biochemical property of CrULP-160 remains unclear. Keyword:Ubiquitin, SUMO, NEDD8, Ubl-specific peptidase, SENP, CrBi-Ub | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:44:13Z (GMT). No. of bitstreams: 1 ntu-99-R97b47212-1.pdf: 3756239 bytes, checksum: 0ae164929de6013a9dc77b0781a6fbc1 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 中文摘要 i
Abstract ii 縮寫表 iii 第一章 緒論 1 1.1泛素與類泛素蛋白質 1 1.1.1 SUMO (small ubiquitin-like modifier) 2 1.1.2 NEDD8 (neural precursor cell-expressed developmentally down-regulated 8) 5 1.2類泛素蛋白質胜肽酶 (ubiquitin-like protein peptidase) 7 1.2.1去泛素化酵素 (Deubiquitinating enzymes) 7 1.2.2 SUMO蛋白酶 (SUMO protease) 8 1.2.3 NEDD8 protease 11 1.2.4 NEDD8與泛素之獨立酵素系統 12 1.3單胞綠藻 (Chlamydomonas reinhardtii) 13 1.4研究動機與方向 13 第二章 材料與方法 14 2.1 Chlamydomonas reinhardtii生長條件 14 2.2 Total RNA 分離及反轉錄聚合酶鏈鎖反應 (RT-PCR) 14 2.3引子設計、基因選殖與表現質體建構 15 2.3.1引子設計 15 2.3.2基因選殖 15 2.3.3表現質體建構 15 2.4重組蛋白質誘導表現 16 2.4.1 BL21 (DE3) 表現系統 16 2.4.2 ArcticExpressTM RP (DE3) 表現系統 17 2.5重組蛋白質之純化方法 17 2.5.1 His6-tag重組蛋白質親和性層析法 17 2.5.2 GST-tag 重組蛋白質親和性層析法 18 2.6蛋白質活性分析 19 2.6.1 SUMO蛋白酶水解活性測試 19 2.6.2大腸桿菌SUMO化系統及去共軛活性測試 19 2.6.3去泛素化酵素活性測試 20 2.6.4 NEDD8蛋白酶活性測試 21 2.7免疫染色 21 2.7.1免疫染色法 21 2.7.2免疫染色退染法 22 第三章 結果 23 3.1類泛素胜肽酶基因選殖與身分鑑定 23 3.1.1 CrULP-160及CrULP-279序列比對與表現質體建構 23 3.1.2 CrULP-160及CrULP-279重組蛋白質表現與純化 23 3.1.3 CrULP-160及CrULP-279不具SUMO蛋白酶之C端序列修飾活性 24 3.1.4 CrULP-279具有水解PolySUMO基質的能力 24 3.1.5 CrBi-Ub之基因選殖與蛋白質純化 25 3.1.6 CrBi-Ub可以被USP2-core及SENP8專一性水解 26 3.1.7 CrULP-160之C端序列修飾活性分析 26 3.1.8 CrDEN1序列比對與表現質體建構 27 3.1.9 CrDEN1之水解活性分析 27 3.2 CrDEN1之基質專一性作用機轉探討 28 3.2.1 CrBi-Ub之突變點質體表現載體建構與蛋白質純化 28 3.2.2類泛素胜肽酶針對His-CrBi-Ub-GST之水解活性比較 29 3.2.3 C端序列之雙甘胺酸在類泛素胜肽酶的辨識上扮演重要角色 30 3.2.4影響類泛素胜肽酶酵素專一性之關鍵胺基酸 31 第四章 討論 33 4.1 CrULP-160及CrULP-279表現與純化 33 4.2 SUMO蛋白酶活性分析 33 4.3 CrULP-160身分確認與活性探討 34 4.4 CrDEN1蛋白質表現與活性分析 35 4.5泛素與NEDD8之類泛素胜肽酶專一性探討 36 未來展望 38 參考文獻 39 圖與表 44 附錄 70 | |
dc.language.iso | zh-TW | |
dc.title | 單胞綠藻中類泛素蛋白質胜肽酶之身分辨認與生化特性分析 | zh_TW |
dc.title | Identification and biochemical characterization of ubiquitin-like protein peptidases in Chlamydomonas reinhardtii | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊榮輝(Rong-Huay Juang),張麗冠(Li-Kwan Chang),陳威戎(Wei-Jung Chen),吳俊宗(Jiunn-Tzong Wu) | |
dc.subject.keyword | 類泛素蛋白質胜肽,酶, | zh_TW |
dc.subject.keyword | ubiquitin-like protein peptidases, | en |
dc.relation.page | 81 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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