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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 | Pei-Tzu Huang | en |
dc.contributor.author | 黃珮慈 | zh_TW |
dc.date.accessioned | 2021-06-08T01:27:04Z | - |
dc.date.copyright | 2014-08-01 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-31 | |
dc.identifier.citation | References
1 Shen, M., Schmitt, S., Buac, D. & Dou, Q. P. Targeting the ubiquitin-proteasome system for cancer therapy. Expert opinion on therapeutic targets 17, 1091-1108 (2013). 2 Oddo, S. The ubiquitin-proteasome system in Alzheimer's disease. Journal of cellular and molecular medicine 12, 363-373 (2008). 3 Dennissen, F. J., Kholod, N. & van Leeuwen, F. W. The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim? Progress in neurobiology 96, 190-207 (2012). 4 Huang, Q. & Figueiredo-Pereira, M. E. Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications. Apoptosis : an international journal on programmed cell death 15, 1292-1311 (2010). 5 Ciechanover, A. & Brundin, P. The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron 40 (2003). 6 Pickart, C. M. & Cohen, R. E. Proteasomes and their kin: proteases in the machine age. Nature reviews. Molecular cell biology 5, 177-187 (2004). 7 Sauer, R. T. & Baker, T. A. AAA+ proteases: ATP-fueled machines of protein destruction. Annual review of biochemistry 80, 587-612 (2011). 8 Dahlmann, B. et al. The multicatalytic proteinase (prosome) is ubiquitous from eukaryotes to archaebacteria. FEBS letters 251, 125-131 (1989). 9 Tamura, T. et al. The first characterization of a eubacterial proteasome: the 20S complex of Rhodococcus. Current biology : CB 5, 766-774 (1995). 10 Knipfer, N. & Shrader, T. E. Inactivation of the 20S proteasome in Mycobacterium smegmatis. Molecular microbiology 25, 375-383 (1997). 11 Nagy, I., Tamura, T., Vanderleyden, J., Baumeister, W. & De Mot, R. The 20S proteasome of Streptomyces coelicolor. Journal of bacteriology 180, 5448-5453 (1998). 12 Brooks, S. A. Functional interactions between mRNA turnover and surveillance and the ubiquitin proteasome system. Wiley interdisciplinary reviews. RNA 1, 240-252 (2010). 13 Wenzel, T. & Baumeister, W. Conformational constraints in protein degradation by the 20S proteasome. Nature structural biology 2, 199-204 (1995). 14 Groll, M. et al. A gated channel into the proteasome core particle. Nature structural biology 7, 1062-1067 (2000). 15 Yu, Y. et al. Interactions of PAN's C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions. The EMBO journal 29, 692-702 (2010). 16 Rabl, J. et al. Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases. Molecular cell 30, 360-368 (2008). 17 Heinemeyer, W., Fischer, M., Krimmer, T., Stachon, U. & Wolf, D. H. The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. The Journal of biological chemistry 272, 25200-25209 (1997). 18 Marques, A. J., Palanimurugan, R., Matias, A. C., Ramos, P. C. & Dohmen, R. J. Catalytic mechanism and assembly of the proteasome. Chemical reviews 109, 1509-1536 (2009). 19 Voges, D., Zwickl, P. & Baumeister, W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annual review of biochemistry 68, 1015-1068 (1999). 20 Arendt, C. S. & Hochstrasser, M. Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. Proceedings of the National Academy of Sciences of the United States of America 94, 7156-7161 (1997). 21 Kloetzel, P. M. Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nature immunology 5, 661-669 (2004). 22 Murata, S. et al. Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 316, 1349-1353 (2007). 23 Gaczynska, M., Rock, K. L. & Goldberg, A. L. Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature 365, 264-267 (1993). 24 He, J. et al. The structure of the 26S proteasome subunit Rpn2 reveals its PC repeat domain as a closed toroid of two concentric alpha-helical rings. Structure 20, 513-521 (2012). 25 Tomko, R. J., Jr. & Hochstrasser, M. Molecular architecture and assembly of the eukaryotic proteasome. Annual review of biochemistry 82, 415-445 (2013). 26 Verma, R. et al. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 298, 611-615 (2002). 27 Tomko, R. J., Jr., Funakoshi, M., Schneider, K., Wang, J. & Hochstrasser, M. Heterohexameric ring arrangement of the eukaryotic proteasomal ATPases: implications for proteasome structure and assembly. Molecular cell 38, 393-403 (2010). 28 Lander, G. C. et al. Complete subunit architecture of the proteasome regulatory particle. Nature 482, 186-191 (2012). 29 Matyskiela, M. E., Lander, G. C. & Martin, A. Conformational switching of the 26S proteasome enables substrate degradation. Nature structural & molecular biology 20, 781-788 (2013). 30 Tian, G. et al. An asymmetric interface between the regulatory and core particles of the proteasome. Nature structural & molecular biology 18, 1259-1267 (2011). 31 Gillette, T. G., Kumar, B., Thompson, D., Slaughter, C. A. & DeMartino, G. N. Differential roles of the COOH termini of AAA subunits of PA700 (19 S regulator) in asymmetric assembly and activation of the 26 S proteasome. The Journal of biological chemistry 283, 31813-31822 (2008). 32 Sledz, P. et al. Structure of the 26S proteasome with ATP-gammaS bound provides insights into the mechanism of nucleotide-dependent substrate translocation. Proceedings of the National Academy of Sciences of the United States of America 110, 7264-7269 (2013). 33 Lee, S. Y., De la Mota-Peynado, A. & Roelofs, J. Loss of Rpt5 protein interactions with the core particle and Nas2 protein causes the formation of faulty proteasomes that are inhibited by Ecm29 protein. The Journal of biological chemistry 286, 36641-36651 (2011). 34 Pollice, A. et al. TBP-1 protects the human oncosuppressor p14ARF from proteasomal degradation. Oncogene 26, 5154-5162 (2007). 35 Lassot, I. et al. The proteasome regulates HIV-1 transcription by both proteolytic and nonproteolytic mechanisms. Molecular cell 25, 369-383 (2007). 36 Corn, P. G., McDonald, E. R., 3rd, Herman, J. G. & El-Deiry, W. S. Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein. Nature genetics 35, 229-237 (2003). 37 Truax, A. D., Koues, O. I., Mentel, M. K. & Greer, S. F. The 19S ATPase S6a (S6'/TBP1) regulates the transcription initiation of class II transactivator. Journal of molecular biology 395, 254-269 (2010). 38 Satoh, T. et al. Roles of proteasomal 19S regulatory particles in promoter loading of thyroid hormone receptor. Biochemical and biophysical research communications 386, 697-702 (2009). 39 Satoh, T. et al. Tat-binding protein-1 (TBP-1), an ATPase of 19S regulatory particles of the 26S proteasome, enhances androgen receptor function in cooperation with TBP-1-interacting protein/Hop2. Endocrinology 150, 3283-3290 (2009). 40 Jakobs, A. et al. Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation. Nucleic acids research 35, e109 (2007). 41 Freemont, P. S., Hanson, I. M. & Trowsdale, J. A novel cysteine-rich sequence motif. Cell 64, 483-484 (1991). 42 Chau, V. et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 1576-1583 (1989). 43 Jin, L., Williamson, A., Banerjee, S., Philipp, I. & Rape, M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133, 653-665 (2008). 44 Matsumoto, M. L. et al. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Molecular cell 39, 477-484 (2010). 45 Williamson, A. et al. Identification of a physiological E2 module for the human anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 106, 18213-18218 (2009). 46 Kim, H. T. et al. Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages. The Journal of biological chemistry 282, 17375-17386 (2007). 47 Mukhopadhyay, D. & Riezman, H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 315, 201-205 (2007). 48 Terrell, J., Shih, S., Dunn, R. & Hicke, L. A function for monoubiquitination in the internalization of a G protein-coupled receptor. Molecular cell 1, 193-202 (1998). 49 Huang, F., Kirkpatrick, D., Jiang, X., Gygi, S. & Sorkin, A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Molecular cell 21, 737-748 (2006). 50 Huang, F., Goh, L. K. & Sorkin, A. EGF receptor ubiquitination is not necessary for its internalization. Proceedings of the National Academy of Sciences of the United States of America 104, 16904-16909 (2007). 51 Hoege, C., Pfander, B., Moldovan, G. L., Pyrowolakis, G. & Jentsch, S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419, 135-141 (2002). 52 Freudenthal, B. D., Gakhar, L., Ramaswamy, S. & Washington, M. T. Structure of monoubiquitinated PCNA and implications for translesion synthesis and DNA polymerase exchange. Nature structural & molecular biology 17, 479-484 (2010). 53 Bienko, M. et al. Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science 310, 1821-1824 (2005). 54 Bienko, M. et al. Regulation of translesion synthesis DNA polymerase eta by monoubiquitination. Molecular cell 37, 396-407 (2010). 55 Huang, T. T. et al. Regulation of monoubiquitinated PCNA by DUB autocleavage. Nature cell biology 8, 339-347 (2006). 56 Huang, M. & D'Andrea, A. D. A new nuclease member of the FAN club. Nature structural & molecular biology 17, 926-928 (2010). 57 Joo, W. et al. Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway. Science 333, 312-316 (2011). 58 Moldovan, G. L. & D'Andrea, A. D. How the fanconi anemia pathway guards the genome. Annual review of genetics 43, 223-249 (2009). 59 Nijman, S. M. et al. The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Molecular cell 17, 331-339 (2005). 60 Dupont, S. et al. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell 136, 123-135 (2009). 61 Winston, J. T. et al. The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes & development 13, 270-283 (1999). 62 Margottin-Goguet, F. et al. Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Developmental cell 4, 813-826 (2003). 63 Li, M. et al. Mono- versus polyubiquitination: differential control of p53 fate by Mdm2. Science 302, 1972-1975 (2003). 64 Plafker, S. M., Plafker, K. S., Weissman, A. M. & Macara, I. G. Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import. The Journal of cell biology 167, 649-659 (2004). 65 Johnson, E. S. Protein modification by SUMO. Annual review of biochemistry 73, 355-382 (2004). 66 Geiss-Friedlander, R. & Melchior, F. Concepts in sumoylation: a decade on. Nature reviews. Molecular cell biology 8, 947-956 (2007). 67 Mahajan, R., Delphin, C., Guan, T., Gerace, L. & Melchior, F. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88, 97-107 (1997). 68 Saitoh, H. et al. Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2. Current biology : CB 8, 121-124 (1998). 69 Hardeland, U., Steinacher, R., Jiricny, J. & Schar, P. Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. The EMBO journal 21, 1456-1464 (2002). 70 Baba, D. et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 435, 979-982 (2005). 71 Steinacher, R. & Schar, P. Functionality of human thymine DNA glycosylase requires SUMO-regulated changes in protein conformation. Current biology : CB 15, 616-623 (2005). 72 Goodson, M. L. et al. Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor. The Journal of biological chemistry 276, 18513-18518 (2001) 73 David, G., Neptune, M. A. & DePinho, R. A. SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological activities. The Journal of biological chemistry 277, 23658-23663 (2002). 74 Ling, Y. et al. Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic acids research 32, 598-610 (2004). 75 Desterro, J. M., Rodriguez, M. S. & Hay, R. T. SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. Mol Cell 2, 233-239 (1998). 76 Wilson, V. G. & Heaton, P. R. Ubiquitin proteolytic system: focus on SUMO. Expert Rev Proteomics 5, 121-135 (2008). 77 Bylebyl, G. R., Belichenko, I. & Johnson, E. S. The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. The Journal of biological chemistry 278, 44113-44120 (2003). 78 Kerscher, O., Felberbaum, R. & Hochstrasser, M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annual review of cell and developmental biology 22, 159-180 (2006). 79 Meluh, P. B. & Koshland, D. Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Molecular biology of the cell 6, 793-807 (1995). 80 Kurepa, J. et al. The small ubiquitin-like modifier (SUMO) protein modification system in Arabidopsis. Accumulation of SUMO1 and -2 conjugates is increased by stress. The Journal of biological chemistry 278, 6862-6872 (2003). 81 Bohren, K. M., Nadkarni, V., Song, J. H., Gabbay, K. H. & Owerbach, D. 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. The Journal of biological chemistry 279, 27233-27238 (2004). 82 Guo, D. et al. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nature genetics 36, 837-841 (2004). 83 Vertegaal, A. C. et al. Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics. Molecular & cellular proteomics : MCP 5, 2298-2310 (2006). 84 Saitoh, H. & Hinchey, J. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. The Journal of biological chemistry 275, 6252-6258 (2000). 85 Sternsdorf, T. et al. PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia. Molecular and cellular biology 19, 5170-5178 (1999). 86 Kamitani, T., Nguyen, H. P., Kito, K., Fukuda-Kamitani, T. & Yeh, E. T. Covalent modification of PML by the sentrin family of ubiquitin-like proteins. The Journal of biological chemistry 273, 3117-3120 (1998). 87 Ayaydin, F. & Dasso, M. Distinct in vivo dynamics of vertebrate SUMO paralogues. Molecular biology of the cell 15, 5208-5218 (2004). 88 Kretz-Remy, C. & Tanguay, R. M. SUMO/sentrin: protein modifiers regulating important cellular functions. Biochemistry and cell biology = Biochimie et biologie cellulaire 77, 299-309 (1999). 89 Sramko, M., Markus, J., Kabat, J., Wolff, L. & Bies, J. Stress-induced inactivation of the c-Myb transcription factor through conjugation of SUMO-2/3 proteins. The Journal of biological chemistry 281, 40065-40075 (2006). 90 Hochstrasser, M. Origin and function of ubiquitin-like proteins. Nature 458, 422-429 (2009). 91 Mukhopadhyay, D. & Dasso, M. Modification in reverse: the SUMO proteases. Trends in biochemical sciences 32, 286-295 (2007). 92 Desterro, J. M., Thomson, J. & Hay, R. T. Ubch9 conjugates SUMO but not ubiquitin. FEBS letters 417, 297-300 (1997). 93 Johnson, E. S. & Blobel, G. Ubc9p is the conjugating enzyme for the ubiquitin-like protein Smt3p. The Journal of biological chemistry 272, 26799-26802 (1997). 94 Gareau, J. R. & Lima, C. D. The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Nature reviews. Molecular cell biology 11, 861-871 (2010). 95 Zhu, J. et al. Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification. The Journal of biological chemistry 283, 29405-29415 (2008). 96 Meulmeester, E., Kunze, M., Hsiao, H. H., Urlaub, H. & Melchior, F. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Molecular cell 30, 610-619 (2008). 97 Hochstrasser, M. SP-RING for SUMO: new functions bloom for a ubiquitin-like protein. Cell 107, 5-8 (2001). 98 Pichler, A., Gast, A., Seeler, J. S., Dejean, A. & Melchior, F. The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell 108, 109-120 (2002). 99 Takahashi, Y., Kahyo, T., Toh, E. A., Yasuda, H. & Kikuchi, Y. Yeast Ull1/Siz1 is a novel SUMO1/Smt3 ligase for septin components and functions as an adaptor between conjugating enzyme and substrates. The Journal of biological chemistry 276, 48973-48977 (2001). 100 Johnson, E. S. & Gupta, A. A. An E3-like factor that promotes SUMO conjugation to the yeast septins. Cell 106, 735-744 (2001). 101 Cheng, C. H. et al. SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes & development 20, 2067-2081 (2006). 102 Potts, P. R. The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination. DNA repair 8, 499-506 (2009). 103 Palvimo, J. J. PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription. Biochemical Society transactions 35, 1405-1408 (2007). 104 Wang, Y. & Dasso, M. SUMOylation and deSUMOylation at a glance. Journal of cell science 122, 4249-4252 (2009). 105 Rodriguez, M. S., Dargemont, C. & Hay, R. T. SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. The Journal of biological chemistry 276, 12654-12659 (2001). 106 Hay, R. T. SUMO: a history of modification. Molecular cell 18, 1-12 (2005). 107 Yang, X. J. & Gregoire, S. A recurrent phospho-sumoyl switch in transcriptional repression and beyond. Molecular cell 23, 779-786 (2006). 108 Hietakangas, V. et al. Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1. Molecular and cellular biology 23, 2953-2968 (2003). 109 Yamashita, D. et al. The transactivating function of peroxisome proliferator-activated receptor gamma is negatively regulated by SUMO conjugation in the amino-terminal domain. Genes to cells : devoted to molecular & cellular mechanisms 9, 1017-1029 (2004). 110 Shalizi, A. et al. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311, 1012-1017 (2006). 111 Mohideen, F. et al. A molecular basis for phosphorylation-dependent SUMO conjugation by the E2 UBC9. Nature structural & molecular biology 16, 945-952 (2009). 112 Yang, S. H., Galanis, A., Witty, J. & Sharrocks, A. D. An extended consensus motif enhances the specificity of substrate modification by SUMO. The EMBO journal 25, 5083-5093 (2006). 113 Pichler, A. et al. SUMO modification of the ubiquitin-conjugating enzyme E2-25K. Nature structural & molecular biology 12, 264-269 (2005). 114 Knipscheer, P. et al. Ubc9 sumoylation regulates SUMO target discrimination. Molecular cell 31, 371-382 (2008). 115 Shen, Z., Pardington-Purtymun, P. E., Comeaux, J. C., Moyzis, R. K. & Chen, D. J. Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system. Genomics 37, 183-186 (1996). 116 Shen, Z., Pardington-Purtymun, P. E., Comeaux, J. C., Moyzis, R. K. & Chen, D. J. UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. Genomics 36, 271-279 (1996). 117 Li, W. et al. Regulation of double-strand break-induced mammalian homologous recombination by UBL1, a RAD51-interacting protein. Nucleic acids research 28, 1145-1153 (2000). 118 Hannich, J. T. et al. Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae. The Journal of biological chemistry 280, 4102-4110 (2005). 119 Hecker, C. M., Rabiller, M., Haglund, K., Bayer, P. & Dikic, I. Specification of SUMO1- and SUMO2-interacting motifs. The Journal of biological chemistry 281, 16117-16127 (2006). 120 Song, J., Durrin, L. K., Wilkinson, T. A., Krontiris, T. G. & Chen, Y. Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proceedings of the National Academy of Sciences of the United States of America 101, 14373-14378 (2004). 121 Lin, D. Y. et al. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Molecular cell 24, 341-354 (2006). 122 Shen, T. H., Lin, H. K., Scaglioni, P. P., Yung, T. M. & Pandolfi, P. P. The mechanisms of PML-nuclear body formation. Molecular cell 24, 331-339 (2006). 123 Ouyang, J., Shi, Y., Valin, A., Xuan, Y. & Gill, G. Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex. Molecular cell 34, 145-154 (2009). 124 Song, J., Zhang, Z., Hu, W. & Chen, Y. Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation. The Journal of biological chemistry 280, 40122-40129 (2005). 125 Baba, D. et al. Crystal structure of SUMO-3-modified thymine-DNA glycosylase. Journal of molecular biology 359, 137-147 (2006). 126 Reverter, D. & Lima, C. D. Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435, 687-692 (2005). 127 Kerscher, O. SUMO junction-what's your function? New insights through SUMO-interacting motifs. EMBO reports 8, 550-555 (2007). 128 Minty, A., Dumont, X., Kaghad, M. & Caput, D. Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif. The Journal of biological chemistry 275, 36316-36323 (2000). 129 Takahashi, H., Hatakeyama, S., Saitoh, H. & Nakayama, K. I. Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein. The Journal of biological chemistry 280, 5611-5621 (2005). 130 Boddy, M. N. et al. Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Molecular and cellular biology 23, 5939-5946 (2003). 131 Raffa, G. D., Wohlschlegel, J., Yates, J. R., 3rd & Boddy, M. N. SUMO-binding motifs mediate the Rad60-dependent response to replicative stress and self-association. The Journal of biological chemistry 281, 27973-27981 (2006). 132 Heideker, J., Perry, J. J. & Boddy, M. N. Genome stability roles of SUMO-targeted ubiquitin ligases. DNA repair 8, 517-524 (2009). 133 Prudden, J. et al. SUMO-targeted ubiquitin ligases in genome stability. The EMBO journal 26, 4089-4101 (2007). 134 Denuc, A., Bosch-Comas, A., Gonzalez-Duarte, R. & Marfany, G. The UBA-UIM domains of the USP25 regulate the enzyme ubiquitination state and modulate substrate recognition. PloS one 4, e5571 (2009). 135 劉邦宇 (2009) SUMO結合受質之蛋白質體學研究,碩士論文,國立台灣大學生命科學院生化科技學系 136 劉昀瑄 (2011) 蛋白酶體19S Rpt5 ATPase 受 SUMO 化修飾之研究,碩士論文,國立台灣大學生命科學院生化科技學系 137 Jakobs, A. et al. Ubc9 fusion-directed SUMOylation (UFDS): a method to analyze function of protein SUMOylation. Nature methods 4, 245-250 (2007). 138 Rizos, H., Woodruff, S. & Kefford, R. F. p14ARF interacts with the SUMO-conjugating enzyme Ubc9 and promotes the sumoylation of its binding partners. Cell cycle 4, 597-603 (2005). 139 高翊軒 (2012) 蛋白酶體19S Rpt5 ATPase 之 SUMO 交互作用模組功能研究,碩士論文,國立台灣大學生命科學院生化科技學系 140 魏 綺 (2013) 蛋白酶體 19S Rpt5 ATPase 受 SUMO化修飾之調控機制研究,碩士論文,國立台灣大學生命科學院生化科技學系 141 Stewart, S. A. et al. Lentivirus-delivered stable gene silencing by RNAi in primary cells. Rna 9, 493-501 (2003). 142 Moore, C. B., Guthrie, E. H., Huang, M. T. & Taxman, D. J. Short hairpin RNA (shRNA): design, delivery, and assessment of gene knockdown. Methods in molecular biology 629, 141-158 (2010). 143 Glickman, M. H. et al. A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3. Cell 94, 615-623 (1998). 144 Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry 72, 248-254 (1976). 145 Schagger, H., Cramer, W. A. & von Jagow, G. Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis. Analytical biochemistry 217, 220-230 (1994). 146 Birnboim, H. C. A rapid alkaline extraction method for the isolation of plasmid DNA. Methods in enzymology 100, 243-255 (1983). 147 Ghosh, S. et al. Method for enhancing solubility of the expressed recombinant proteins in Escherichia coli. BioTechniques 37, 418, 420, 422-413 (2004). 148 Stadtmueller, B. M. et al. Structural models for interactions between the 20S proteasome and its PAN/19S activators. The Journal of biological chemistry 285, 13-17 (2010). 149 Besche, H. C., Peth, A. & Goldberg, A. L. Getting to first base in proteasome assembly. Cell 138, 25-28 (2009). 150 Schimmel, J. et al. The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle. Molecular & cellular proteomics : MCP 7, 2107-2122 (2008). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18800 | - |
dc.description.abstract | 蛋白酶體 (proteasome) 由20S core particle (CP) 和19S regulatory particle (RP)所組成。而19S regulatory particle的基座(base)由六個Rpt次單元體Rpt1~6共同組成。Rpt5 (19S regulatory particle ATPase 5) 屬於AAA-ATPase family,具有辨識泛素鏈、對蛋白質進行去摺疊、以及運送目標蛋白質等功能。本實驗室先前的研究發現Rpt5在COS7細胞株中會受到SUMO2的修飾,而且也可以利用大腸桿菌系統將Rpt5進行SUMO1跟SUMO2的修飾。本研究更進一步以 in vitro sumoylation assay證明,在試管中Rpt5重組蛋白可以被SUMO1修飾。
在蛋白酶體降解蛋白質的過程中,ATP的結合與水解扮演重要的角色,因此本研究想要探討SUMO修飾是否會影響Rpt5的ATPase活性。實驗結果顯示,在受到SUMO修飾之後,Rpt5的ATPase活性會下降。此外,Rpt5上有六個可能為SUMO-interacting motif (SIM) 的序列。先前的研究指出將Rpt5的SIM3突變之後,會使Rpt5在大腸桿菌系統中被SUMO1修飾的情形顯著下降;但在HEK293T細胞中重複此實驗時,卻發現Rpt5的SUMO修飾並未下降。為了排除HEK293T內生性Rpt5的干擾,本研究嘗試使用shRNA來knockdown 內生性Rpt5的表現。但是實驗結果顯示Rpt5 knockdown的細胞株無法存活,因此仍無法充分證實SIM3是否參與Rpt5之SUMO修飾作用。 | zh_TW |
dc.description.abstract | The 26S proteasome is composed of 20S core particle (CP) capped with 19S regulatory particle (RP). Regulatory particle triple-A ATPase 5 (Rpt5) is one of the subunits of the 19S RP, which forms the base of 19S RP together with Rpt1, Rpt2, Rpt3, Rpt4 and Rpt6. The 19S base performs several functions, such as polyubiquitin chain recognition, substrate unfolding, gate opening and also translocation of target proteins into 20S CP. Our previous study has revealed that Rpt5 was modified by small ubiquitin-like modifier 2 (SUMO2) in COS7 cells, and modified by SUMO1 and SUMO2 in the E. coli sumoylation system. In the present study, the in vitro sumoylation assay further demonstrated that recombinant Rpt5 can be modified by SUMO1.
Because ATP binding and hydrolysis play critical roles in the regulation of proteasome function, this study was aimed to examine whether SUMO modification may affect the ATPase activity of Rpt5. The result showed that the ATPase activity of Rpt5 was reduced by SUMO2 modification. Furthermore, Rpt5 was found to contain several putative SUMO interacting motifs (SIMs). Although previous in vitro experimental results showed that sumoylation of Rpt5 by SUMO1 was markedly reduced while SIM3 was mutated, the level of Rpt5 sumoylation was not lowered when SIM3 was mutated in HEK293T cells. To rule out the possibility that endogenous Rpt5 might interfere with the observation of sumoylation pattern, shRNAs were applied to knockdown the expression level of endogenous Rpt5. However, the cells with inhibited Rpt5 expression were not viable. Therefore, whether SIM3 is involved in Rpt5 sumoylation remain elusive. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:27:04Z (GMT). No. of bitstreams: 1 ntu-103-R01b22001-1.pdf: 65381403 bytes, checksum: 866027770e561d7bba022924285a8b5b (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | Contents
Introduction 1 1. The ubiquitin-proteasome system 1 2. The proteasome 1 2.1 20S core particle 2 2.2 19S regulatory particle 3 2.3 Regulatory particle triple-A ATPase 5 (Rpt5) 6 3. The ubiquitination pathway 8 4. The sumoylation modification 10 4.1 The SUMO Protein 12 4.2 The sumoylation pathway 13 4.3 SUMO consensus motif 15 4.4 SUMO interacting motif 16 4.5 Crosstalk between SUMO and ubiquitin pathway 18 5. Specific aims of the study 19 Materials and Methods 22 1. Bacterial system 22 2. Cell system 23 3. Plasmid DNA preparation 24 4. Preparation of competent cell 25 5. Expression of heterologous Rpt5 protein in E.coli transformation 25 6. IPTG induction 26 7. Cell disruption by FRENCHR Press (high-pressure homogenizer) 27 8. Purification of recombinant protein 27 9. Bradford protein quantification 30 10. SDS-PAGE 31 11. Native PAGE 31 12. Western blotting (Immunoblotting) 32 13. Antibody stripping and reprobing 32 14. ATPase activity assay 33 15. In vitro sumoylation assay 33 16. Mammalian cell culture 34 17. Cryopreservation 34 18. Preparation of shRNA 34 19. Transfection 35 20. Cell lysis 35 Results 37 1. Examine whether sumoylation will affect the ATPase activity of Rpt5 37 1.1 Expression of Rpt5 and Rpt5-SUMO2 37 1.2 Purification of Rpt5 and Rpt5-SUMO2 38 1.3 Rpt5 and Rpt5-SUMO2 ATPase activity assay 39 2. Use in vitro sumoylation system to observe the sumoylation of Rpt5 40 2.1 Purification of Sae1/2, Ubc9, SUMO1 and SUMO2 40 2.2 In vitro sumoylation assay of Rpt5m9ok9okokooooooooooook 41 3. Examine Rpt5 sumoylation site in HEK293T cell 41 Discussion 42 1. Addition of glycylglycine did not enhance the expression of Rpt5 protein in E. coli 42 2. Purification of Rpt5 and Rpt5-SUMO2 protein by anion exchange column and affinity chromatography 43 3. Sumoylation may affect the ATPase activity of Rpt5 44 4. Rpt5 can be modified by SUMO1 45 5. Knockdown of Rpt5 by shRNA may not be viable in cells 47 References 61 Appendix 72 | |
dc.language.iso | en | |
dc.title | 蛋白酶體19S Rpt5 ATPase受SUMO修飾後之活性影響研究 | zh_TW |
dc.title | Study of the Proteasome 19S Rpt5 ATPase Activity Affected by SUMO Modification | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張麗冠(Li-Kwan Chang),廖憶純(Yi-Chun Liao),陳威戎(Wei-Jung Chen) | |
dc.subject.keyword | Proteasome,Rpt5,SUMO,sumoylation,SIM, | zh_TW |
dc.relation.page | 77 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2014-07-31 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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