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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
dc.contributor.author | Min-Jan Chiu | en |
dc.contributor.author | 邱敏然 | zh_TW |
dc.date.accessioned | 2021-06-13T03:36:36Z | - |
dc.date.available | 2006-09-17 | |
dc.date.copyright | 2006-07-31 | |
dc.date.issued | 2006 | |
dc.date.submitted | 2006-07-26 | |
dc.identifier.citation | Bai, C., Sen, P., Hofmann, K., Ma, L., Goebl, M., Harper, J. W., and Elledge, S. J. (1996). SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86, 263-274.
Bouhouche, A., Benomar, A., Bouslam, N., Chkili, T., and Yahyaoui, M. (2006). Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. J Med Genet. Camasses, A., Bogdanova, A., Shevchenko, A., and Zachariae, W. (2003). The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol Cell 12, 87-100. Choi, K. M., McMahon, L. P., and Lawrence, J. C., Jr. (2003). Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor. J Biol Chem 278, 19667-19673. Craig, E. A. (2003). Eukaryotic chaperonins: lubricating the folding of WD-repeat proteins. Curr Biol 13, R904-905. Dunn, A. Y., Melville, M. W., and Frydman, J. (2001). Review: cellular substrates of the eukaryotic chaperonin TRiC/CCT. J Struct Biol 135, 176-184. Fares, M. A., and Wolfe, K. H. (2003). Positive selection and subfunctionalization of duplicated CCT chaperonin subunits. Mol Biol Evol 20, 1588-1597. Feldman, D. E., Spiess, C., Howard, D. E., and Frydman, J. (2003). Tumorigenic mutations in VHL disrupt folding in vivo by interfering with chaperonin binding. Mol Cell 12, 1213-1224. Feldman, D. E., Thulasiraman, V., Ferreyra, R. G., and Frydman, J. (1999). Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TRiC. Mol Cell 4, 1051-1061. Fenton, W. A., and Horwich, A. L. (1997). GroEL-mediated protein folding. Protein Sci 6, 743-760. Gonczy, P., Echeverri, C., Oegema, K., Coulson, A., Jones, S. J., Copley, R. R., Duperon, J., Oegema, J., Brehm, M., Cassin, E., et al. (2000). Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408, 331-336. Gonczy, P., Schnabel, H., Kaletta, T., Amores, A. D., Hyman, T., and Schnabel, R. (1999). Dissection of cell division processes in the one cell stage Caenorhabditis elegans embryo by mutational analysis. J Cell Biol 144, 927-946. Halaschek-Wiener, J., Khattra, J. S., McKay, S., Pouzyrev, A., Stott, J. M., Yang, G. S., Holt, R. A., Jones, S. J., Marra, M. A., Brooks-Wilson, A. R., and Riddle, D. L. (2005). Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15, 603-615. Hara, K., Maruki, Y., Long, X., Yoshino, K., Oshiro, N., Hidayat, S., Tokunaga, C., Avruch, J., and Yonezawa, K. (2002). Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110, 177-189. Hartl, F. U. (1996). Molecular chaperones in cellular protein folding. Nature 381, 571-579. Ho, Y., Gruhler, A., Heilbut, A., Bader, G. D., Moore, L., Adams, S. L., Millar, A., Taylor, P., Bennett, K., Boutilier, K., et al. (2002). Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180-183. Houry, W. A., Frishman, D., Eckerskorn, C., Lottspeich, F., and Hartl, F. U. (1999). Identification of in vivo substrates of the chaperonin GroEL. Nature 402, 147-154. Jia, K., Chen, D., and Riddle, D. L. (2004). The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131, 3897-3906. Kabir, M. A., Kaminska, J., Segel, G. B., Bethlendy, G., Lin, P., Della Seta, F., Blegen, C., Swiderek, K. M., Zoladek, T., Arndt, K. T., and Sherman, F. (2005). Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae. Yeast 22, 219-239. Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M., et al. (2003). Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421, 231-237. Kiger, A. A., Baum, B., Jones, S., Jones, M. R., Coulson, A., Echeverri, C., and Perrimon, N. (2003). A functional genomic analysis of cell morphology using RNA interference. J Biol 2, 27. Kim, D. H., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-175. Kim, D. H., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K. V., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2003). GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11, 895-904. Kim, J. C., Ou, Y. Y., Badano, J. L., Esmail, M. A., Leitch, C. C., Fiedrich, E., Beales, P. L., Archibald, J. M., Katsanis, N., Rattner, J. B., and Leroux, M. R. (2005). MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis. J Cell Sci 118, 1007-1020. Kraft, C., Vodermaier, H. C., Maurer-Stroh, S., Eisenhaber, F., and Peters, J. M. (2005). The WD40 propeller domain of Cdh1 functions as a destruction box receptor for APC/C substrates. Mol Cell 18, 543-553. Kubota, H., Hynes, G., Carne, A., Ashworth, A., and Willison, K. (1994). Identification of six Tcp-1-related genes encoding divergent subunits of the TCP-1-containing chaperonin. Curr Biol 4, 89-99. Lee, M. J., Stephenson, D. A., Groves, M. J., Sweeney, M. G., Davis, M. B., An, S. F., Houlden, H., Salih, M. A., Timmerman, V., de Jonghe, P., et al. (2003). Hereditary sensory neuropathy is caused by a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4) gene. Hum Mol Genet 12, 1917-1925. Leroux, M. R., and Candido, E. P. (1997). Subunit characterization of the Caenorhabditis elegans chaperonin containing TCP-1 and expression pattern of the gene encoding CCT-1. Biochem Biophys Res Commun 241, 687-692. Leroux, M. R., and Hartl, F. U. (2000). Protein folding: versatility of the cytosolic chaperonin TRiC/CCT. Curr Biol 10, R260-264. Llorca, O., Martin-Benito, J., Gomez-Puertas, P., Ritco-Vonsovici, M., Willison, K. R., Carrascosa, J. L., and Valpuesta, J. M. (2001). Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin. J Struct Biol 135, 205-218. Llorca, O., Martin-Benito, J., Ritco-Vonsovici, M., Grantham, J., Hynes, G. M., Willison, K. R., Carrascosa, J. L., and Valpuesta, J. M. (2000). Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations. Embo J 19, 5971-5979. Llorca, O., McCormack, E. A., Hynes, G., Grantham, J., Cordell, J., Carrascosa, J. L., Willison, K. R., Fernandez, J. J., and Valpuesta, J. M. (1999). Eukaryotic type II chaperonin CCT interacts with actin through specific subunits. Nature 402, 693-696. Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., and Hall, M. N. (2002). Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10, 457-468. Long, X., Spycher, C., Han, Z. S., Rose, A. M., Muller, F., and Avruch, J. (2002). TOR deficiency in C. elegans causes developmental arrest and intestinal atrophy by inhibition of mRNA translation. Curr Biol 12, 1448-1461. Lum, L., Yao, S., Mozer, B., Rovescalli, A., Von Kessler, D., Nirenberg, M., and Beachy, P. A. (2003). Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells. Science 299, 2039-2045. Martin, J., and Hartl, F. U. (1997). Chaperone-assisted protein folding. Curr Opin Struct Biol 7, 41-52. Melville, M. W., McClellan, A. J., Meyer, A. S., Darveau, A., and Frydman, J. (2003). The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex. Mol Cell Biol 23, 3141-3151. Neer, E. J., Schmidt, C. J., Nambudripad, R., and Smith, T. F. (1994). The ancient regulatory-protein family of WD-repeat proteins. Nature 371, 297-300. Nojima, H., Tokunaga, C., Eguchi, S., Oshiro, N., Hidayat, S., Yoshino, K., Hara, K., Tanaka, N., Avruch, J., and Yonezawa, K. (2003). The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 278, 15461-15464. Orlicky, S., Tang, X., Willems, A., Tyers, M., and Sicheri, F. (2003). Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase. Cell 112, 243-256. Pickart, C. M. (2001). Mechanisms underlying ubiquitination. Annu Rev Biochem 70, 503-533. Sarbassov, D. D., Ali, S. M., Kim, D. H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2004). Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14, 1296-1302. Schalm, S. S., Fingar, D. C., Sabatini, D. M., and Blenis, J. (2003). TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol 13, 797-806. Schmidt, A., Kunz, J., and Hall, M. N. (1996). TOR2 is required for organization of the actin cytoskeleton in yeast. Proc Natl Acad Sci U S A 93, 13780-13785. Schuller, E., Gulesserian, T., Seidl, R., Cairns, N., and Lube, G. (2001). Brain t-complex polypeptide 1 (TCP- 1) related to its natural substrate beta1 tubulin is decreased in Alzheimer's disease. Life Sci 69, 263-270. Siegers, K., Bolter, B., Schwarz, J. P., Bottcher, U. M., Guha, S., and Hartl, F. U. (2003). TRiC/CCT cooperates with different upstream chaperones in the folding of distinct protein classes. Embo J 22, 5230-5240. Skowyra, D., Craig, K. L., Tyers, M., Elledge, S. J., and Harper, J. W. (1997). F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell 91, 209-219. Sonnichsen, B., Koski, L. B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A. M., Artelt, J., Bettencourt, P., Cassin, E., et al. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462-469. Soti, C., Nagy, E., Giricz, Z., Vigh, L., Csermely, P., and Ferdinandy, P. (2005a). Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146, 769-780. Soti, C., Pal, C., Papp, B., and Csermely, P. (2005b). Molecular chaperones as regulatory elements of cellular networks. Curr Opin Cell Biol 17, 210-215. Stebbins, C. E., Kaelin, W. G., Jr., and Pavletich, N. P. (1999). Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science 284, 455-461. Strome, S., and Wood, W. B. (1983). Generation of asymmetry and segregation of germ-line granules in early C. elegans embryos. Cell 35, 15-25. Thulasiraman, V., Yang, C. F., and Frydman, J. (1999). In vivo newly translated polypeptides are sequestered in a protected folding environment. Embo J 18, 85-95. Valpuesta, J. M., Martin-Benito, J., Gomez-Puertas, P., Carrascosa, J. L., and Willison, K. R. (2002). Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett 529, 11-16. Varshavsky, A. (1991). Naming a targeting signal. Cell 64, 13-15. Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., and Muller, F. (2003). Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426, 620. Wullschleger, S., Loewith, R., Oppliger, W., and Hall, M. N. (2005). Molecular organization of target of rapamycin complex 2. J Biol Chem 280, 30697-30704. Wullschegers, S, Loewith, R, and Hall, M. N. (2006). TOR signaling in growth and metabolism. Cell 124,471-484 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32204 | - |
dc.description.abstract | CCT (Chaperonin contain T-complex polypeptide 1又名TriC)是真核生物特有的chaperonin,由8個次單元組成,共組一個16-mer的雙環結構複合體,協助新合成蛋白的摺疊或是變性蛋白的再褶疊。目前已知actin,tubulin,以及其它蛋白經過CCT摺疊而活化。且陸續有新的蛋白發現和CCT作用,其中,許多是具有WD repeat doamain的蛋白。CCT各次單元序列之間的差異,暗示各單元扮演不同的功能,可能和不同受質作用。我们在線蟲( Caenorhabditis elegans)分別對各次單元進行knockdown,發現這些基因皆為早期胚胎發育所需,細胞分裂時,如紡錘絲的形成,染色體的分離,細胞質分裂等過程都受到影響,表現pleiotropic的性狀。我们的觀察顯示tubulin的表現量可能減少。然而,我们發現knockdown後,線蟲會滯留在幼蟲時期,生殖腺退化,且消化道澎大並充滿未消化的細菌,對機械性外力敏感。這些性狀和let-363(CeTOR)突變株有相似之處。TOR是細胞生長的中心調控者,負責生合成核醣體,轉譯等作用。因此,我们猜測CCT可能影響細胞的生長與代謝。 | zh_TW |
dc.description.abstract | Eukayotic chaperonin CCT (Chaperonin contain T-complex polypeptide also named TriC),established by 8 subunits,is a 16- mer double-ring complex. CCT contributes to the folding of newly synthesized proteins and the refolding of denatured proteins. Actin, tubulin and several other proteins are well known activated by CCT folding. New proteins are still found to interact with CCT, and many of them WD repeat proteins. CCT subunits are different in protein sequences, suggesting specification between them. We knockdown the subunits in Caenorhabditis elegans and found them all essential for early embryogenesis. We found defects in spindle fiber formation,chromosome segregation,cytokinesis and others,indicating a pleiotropic effect. Our observation also suggests deficiency in tubulin. However, the progeny arrest in larval stage with degenerate gonads and intestinal lumens enlarged by undigested bacteria. And they are sensitive to mechanical pressure. Similar phenotypes are in let-363 (CeTOR) mutant. TOR is the central controller of cell growth. We suggest a role of CCT in cell growth and metabolism. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T03:36:36Z (GMT). No. of bitstreams: 1 ntu-95-R91225016-1.pdf: 3102366 bytes, checksum: 6ce2ce81c13daa0eca2a9f23ed49ce01 (MD5) Previous issue date: 2006 | en |
dc.description.tableofcontents | 中文摘要 1
Abstract 2 引言 3 CCT是真核生物特有的Chaperonin 3 細胞骨架蛋白actin及tubulin是CCT的受質 3 目前其他已知的CCT受質 4 CCT和ubiquitin ligase、WD repeat蛋白之間的關聯性 4 WD repeat 蛋白質家族 5 Ubiquitin 蛋白質降解系統 6 CCT與TOR signaling pathway之間的關聯 7 TOR signaling 的介紹 8 CCT與疾病的關聯 11 細胞分裂 12 線蟲早期胚胎為研究細胞分裂的理想系統 14 材料與方法 16 線蟲 16 Plasmid 製備 16 RNA-mediated interference 17 Time-lapse 螢光顯微鏡 17 性狀分析 17 結果 18 CCT是高度保守性的基因 18 CCT基因表現模式 18 CCT RNAi 降低產卵率 19 CCT RNAi 造成胚胎死亡 20 CCT RNAi 造成幼蟲生長遲滯 20 CCT RNAi 造成生殖腺發育退化 20 腸道內堆積大量bacteria且口徑加大 21 Pleiotropic defect in early stage embryo 21 Spindle fiber 無法形成 21 其它常見早期胚胎性狀 23 討論 24 CCT RNAi 和CeTOR mutant (let -363)性狀相似 24 CCT影響早期胚胎發育 25 CCT影響成蟲及幼蟲發育 26 CCT可能造成tubulin aggregation 27 疾病治療的可能性 28 圖 表 29 參考文獻 41 | |
dc.language.iso | zh-TW | |
dc.title | CCT chaperonin在線蟲早期胚胎發育的功能分析 | zh_TW |
dc.title | Functional analysis of CCT chaperonin
in early embryogenesis in Caenorhabditis elegans | en |
dc.type | Thesis | |
dc.date.schoolyear | 94-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 蘇銘燦(Ming-Tsan Su),李銘仁(Ming-Jen Lee) | |
dc.subject.keyword | 線蟲,細胞骨架,胚胎發育,細胞生長,細胞週期, | zh_TW |
dc.subject.keyword | C. elegans,CCT,Chaperonin,TOR,tubulin,embryogenesis,RNA intreference,WD repeat,cell growth, | en |
dc.relation.page | 46 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2006-07-27 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
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