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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧述諄(Shu-Chun Teng) | |
| dc.contributor.author | Yu-Jung Chen | en |
| dc.contributor.author | 陳郁蓉 | zh_TW |
| dc.date.accessioned | 2021-06-17T06:41:24Z | - |
| dc.date.available | 2019-09-04 | |
| dc.date.copyright | 2018-09-04 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-15 | |
| dc.identifier.citation | Batisse, J., C. Batisse, A. Budd, B. Bottcher and E. Hurt (2009). 'Purification of nuclear poly(A)-binding protein Nab2 reveals association with the yeast transcriptome and a messenger ribonucleoprotein core structure.' J Biol Chem 284(50): 34911-34917.
Borkovich, K. A., F. W. Farrelly, D. B. Finkelstein, J. Taulien and S. Lindquist (1989). 'hsp82 is an essential protein that is required in higher concentrations for growth of cells at higher temperatures.' Molecular and Cellular Biology 9(9): 3919-3930. Catlett, M. G. and K. B. Kaplan (2006). 'Sgt1p Is a Unique Co-chaperone That Acts as a Client Adaptor to Link Hsp90 to Skp1p.' Journal of Biological Chemistry 281(44): 33739-33748. Chiti, F. and C. M. Dobson (2006). 'Protein Misfolding, Functional Amyloid, and Human Disease.' Annual Review of Biochemistry 75(1): 333-366. de Cabo, R., D. Carmona-Gutierrez, M. Bernier, M. N. Hall and F. Madeo (2014). 'The search for antiaging interventions: from elixirs to fasting regimens.' Cell 157(7): 1515-1526. Dobson, C. M. (2003). 'Protein folding and misfolding.' Nature 426: 884. el Moualij, B., C. Duyckaerts, J. Lamotte-Brasseur and F. E. Sluse (1997). 'Phylogenetic classification of the mitochondrial carrier family of Saccharomyces cerevisiae.' Yeast 13(6): 573-581. Fabrizio, P., F. Pozza, S. D. Pletcher, C. M. Gendron and V. D. Longo (2001). 'Regulation of longevity and stress resistance by Sch9 in yeast.' Science 292(5515): 288-290. Fontana, L., L. Partridge and V. D. Longo (2010). 'Extending Healthy Life Span—From Yeast to Humans.' Science 328: 321-326. Francis, B. R. and P. E. Thorsness (2011). 'Hsp90 and mitochondrial proteases Yme1 and Yta10/12 participate in ATP synthase assembly in Saccharomyces cerevisiae.' Mitochondrion 11(4): 587-600. Franzmann, T. M., M. Jahnel, A. Pozniakovsky, J. Mahamid, A. S. Holehouse, E. Nuske, D. Richter, W. Baumeister, S. W. Grill, R. V. Pappu, A. A. Hyman and S. Alberti (2018). 'Phase separation of a yeast prion protein promotes cellular fitness.' Science 359(6371). Fromont-Racine, M., J. C. Rain and P. Legrain (1997). 'Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens.' Nat Genet 16(3): 277-282. Gavin, A. C., P. Aloy, P. Grandi, R. Krause, M. Boesche, M. Marzioch, C. Rau, L. J. Jensen, S. Bastuck, B. Dumpelfeld, A. Edelmann, M. A. Heurtier, V. Hoffman, C. Hoefert, K. Klein, M. Hudak, A. M. Michon, M. Schelder, M. Schirle, M. Remor, T. Rudi, S. Hooper, A. Bauer, T. Bouwmeester, G. Casari, G. Drewes, G. Neubauer, J. M. Rick, B. Kuster, P. Bork, R. B. Russell and G. Superti-Furga (2006). 'Proteome survey reveals modularity of the yeast cell machinery.' Nature 440(7084): 631-636. Grammatikakis, N., J. H. Lin, A. Grammatikakis, P. N. Tsichlis and B. H. Cochran (1999). 'p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function.' Mol Cell Biol 19(3): 1661-1672. Harman, D. (1981). 'The aging process.' Proceedings of the National Academy of Sciences of the United States of America 78(11): 7124-7128. Johnson, B. D., R. J. Schumacher, E. D. Ross and D. O. Toft (1998). 'Hop modulates Hsp70/Hsp90 interactions in protein folding.' J Biol Chem 273(6): 3679-3686. Kaeberlein, M. (2010). 'Lessons on longevity from budding yeast.' Nature 464(7288): 513-519. Kershaw, C. J., J. L. Costello, D. Talavera, W. Rowe, L. M. Castelli, P. F. Sims, C. M. Grant, M. P. Ashe, S. J. Hubbard and G. D. Pavitt (2015). 'Integrated multi-omics analyses reveal the pleiotropic nature of the control of gene expression by Puf3p.' Sci Rep 5: 15518. Li, J., K. Richter and J. Buchner (2011). 'Mixed Hsp90-cochaperone complexes are important for the progression of the reaction cycle.' Nat Struct Mol Biol 18(1): 61-66. Li, J., J. Soroka and J. Buchner (2012). 'The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperones.' Biochim Biophys Acta 1823(3): 624-635. Longtine, M. S., A. McKenzie, 3rd, D. J. Demarini, N. G. Shah, A. Wach, A. Brachat, P. Philippsen and J. R. Pringle (1998). 'Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.' Yeast 14(10): 953-961. Lopez-Otin, C., M. A. Blasco, L. Partridge, M. Serrano and G. Kroemer (2013). 'The hallmarks of aging.' Cell 153(6): 1194-1217. Marobbio, C. M., G. Agrimi, F. M. Lasorsa and F. Palmieri (2003). 'Identification and functional reconstitution of yeast mitochondrial carrier for S-adenosylmethionine.' EMBO J 22(22): 5975-5982. McClellan, A. J., Y. Xia, A. M. Deutschbauer, R. W. Davis, M. Gerstein and J. Frydman (2007). 'Diverse Cellular Functions of the Hsp90 Molecular Chaperone Uncovered Using Systems Approaches.' Cell 131(1): 121-135. O'Connell, J. D., M. Tsechansky, A. Royal, D. R. Boutz, A. D. Ellington and E. M. Marcotte (2014). 'A proteomic survey of widespread protein aggregation in yeast.' Mol Biosyst 10(4): 851-861. Obata, F. and M. Miura (2015). 'Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan.' Nat Commun 6: 8332. Ogawa, T., R. Tsubakiyama, M. Kanai, T. Koyama, T. Fujii, H. Iefuji, T. Soga, K. Kume, T. Miyakawa, D. Hirata and M. Mizunuma (2016). 'Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK.' Proc Natl Acad Sci U S A 113(42): 11913-11918. Phalip, V., I. Kuhn, Y. Lemoine and J. M. Jeltsch (1999). 'Characterization of the biotin biosynthesis pathway in Saccharomyces cerevisiae and evidence for a cluster containing BIO5, a novel gene involved in vitamer uptake.' Gene 232(1): 43-51. Ross, C. A. and M. A. Poirier (2004). 'Protein aggregation and neurodegenerative disease.' Nature Medicine 10: S10. Sahasrabudhe, P., J. Rohrberg, M. M. Biebl, D. A. Rutz and J. Buchner (2017). 'The Plasticity of the Hsp90 Co-chaperone System.' Mol Cell 67(6): 947-961 e945. Santamaria, E., M. A. Avila, M. U. Latasa, A. Rubio, A. Martin-Duce, S. C. Lu, J. M. Mato and F. J. Corrales (2003). 'Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine.' Proc Natl Acad Sci U S A 100(6): 3065-3070. Schopf, F. H., M. M. Biebl and J. Buchner (2017). 'The HSP90 chaperone machinery.' Nature Reviews Molecular Cell Biology 18: 345. Sia, R. A. and A. P. Mitchell (1995). 'Stimulation of later functions of the yeast meiotic protein kinase Ime2p by the IDS2 gene product.' Mol Cell Biol 15(10): 5279-5287. Soroka, J., S. K. Wandinger, N. Mausbacher, T. Schreiber, K. Richter, H. Daub and J. Buchner (2012). 'Conformational switching of the molecular chaperone Hsp90 via regulated phosphorylation.' Mol Cell 45(4): 517-528. Taipale, M., I. Krykbaeva, M. Koeva, C. Kayatekin, K. D. Westover, G. I. Karras and S. Lindquist (2012). 'Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.' Cell 150(5): 987-1001. Thomas, D. and Y. Surdin-Kerjan (1991). 'The synthesis of the two S-adenosyl-methionine synthetases is differently regulated in Saccharomyces cerevisiae.' Mol Gen Genet 226(1-2): 224-232. Thomas, D. and Y. Surdin-Kerjan (1997). 'Metabolism of sulfur amino acids in Saccharomyces cerevisiae.' Microbiology and Molecular Biology Reviews 61(4): 503-532. Wegele, H., S. K. Wandinger, A. B. Schmid, J. Reinstein and J. Buchner (2006). 'Substrate transfer from the chaperone Hsp70 to Hsp90.' J Mol Biol 356(3): 802-811. Wei, M., P. Fabrizio, J. Hu, H. Ge, C. Cheng, L. Li and V. D. Longo (2008). 'Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9.' PLoS Genet 4(1): e13. Wei, M., P. Fabrizio, F. Madia, J. Hu, H. Ge, L. M. Li and V. D. Longo (2009). 'Tor1/Sch9-Regulated Carbon Source Substitution Is as Effective as Calorie Restriction in Life Span Extension.' PLOS Genetics 5(5): e1000467. Zhao, R., M. Davey, Y.-C. Hsu, P. Kaplanek, A. Tong, A. B. Parsons, N. Krogan, G. Cagney, D. Mai, J. Greenblatt, C. Boone, A. Emili and W. A. Houry (2005). 'Navigating the Chaperone Network: An Integrative Map of Physical and Genetic Interactions Mediated by the Hsp90 Chaperone.' Cell 120(5): 715-727. Zuehlke, A. D., M. Reidy, C. Lin, P. LaPointe, S. Alsomairy, D. J. Lee, G. M. Rivera-Marquez, K. Beebe, T. Prince, S. Lee, J. B. Trepel, W. Xu, J. Johnson, D. Masison and L. Neckers (2017). 'An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans.' Nature Communications 8: 15328. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72419 | - |
| dc.description.abstract | 熱休克蛋白90 (Hsp90) 是真核生物中具高度保留性的分子，在許多細胞內分子機制中扮演著重要的角色，如信號傳導和細胞增殖等等。此外，熱休克蛋白90也參與了眾多蛋白質的折疊、裝配與成熟。在其作用的機制當中，需要大量的蛋白因子幫忙，稱之為輔助性熱休克蛋白，這些蛋白會根據其功能參與熱休克蛋白Hsp90的構象循環並調節其活性。先前的研究表示，IME2依賴性信號蛋白(Ids2)可能是Hsp90的輔助性熱休克蛋白，甚至於其在胺基酸148處位點的磷酸化會影響Ids2和Hsp90之間的相互作用，然而，其中的分子機制仍然尚未知曉。因此，我們從和Ids2有交互作用的蛋白質當中篩選，希望能夠發現需依賴Ids2-Hsp90複合物來進行蛋白折疊的潛在受質。於篩選中發現，S-腺苷甲硫氨酸合酶1 (Sam1) 在ids2Δ菌株中，蛋白質表現和酵素功能均會下降，進一步於螢光顯微鏡中發現，Sam1會在細胞中形成蛋白聚集，然而，有趣的是，ids2的磷酸化突變株並不會影響Sam1的蛋白質表現，卻會損害它的功能。除此之外，Ids2和Hsc82以及Sam1三者之間的物理交互作用已經由免疫沉澱法得到證實。結合上述證據，Ids2可能會作為輔助性熱休克蛋白來影響Ids2-Hsc82-Sam1 comeplex的活性。 | zh_TW |
| dc.description.abstract | We have previously found a protein, Ids2 (IME2-dependent signaling protein), de-phosphorylated under CR, and loss of Ids2 leads to CLS extension, mitochondrial defects, and heat intolerant phenotype. The analysis of tandem affinity purification of Ids2 revealed its interaction with Hsp90, including Hsc82 and Hsp82 in yeast. Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone in eukaryotes, which is necessary for folding, maturation, and activity of numerous client proteins. Thus, it plays an essential role in many physiological processes such as signal transduction and cell proliferation. Such chaperone function requires a large group of helper proteins, termed co-chaperones, which participate in the various conformational state of the HSP90 chaperone cycle and regulate its activity. Previous evidence indicated that Ids2 may serve as a co-chaperone of HSP90 and its phosphorylation at residue 148 may affect the interaction between Ids2 and HSP90. However, the molecular mechanism remains elusive. I therefore screened interacting partners of Ids2, hoping to discover potential clients whose protein folding is dependent on the Ids2-HSP90 complex. S-adenosylmethionine synthase 1 (Sam1) was found that both the protein expression and enzymatic function of Sam1 decreased in ids2∆ strains. The further evidence showed that deletion of IDS2 led to foci formation of Sam1; nevertheless, interestingly, ids2 phosphor-mimicking mutation did not influence the protein expression of TAP-tagged Sam1 but did damage the function of it. Besides, the physical interaction was confirmed between Ids2, Hsc82, and Sam1. Together, Ids2 may function as a co-chaperone to affect the activity of the Ids2-Hsc82-Sam1 complex. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T06:41:24Z (GMT). No. of bitstreams: 1 ntu-107-R05445120-1.pdf: 1884185 bytes, checksum: 2fefc84d87d6cc77212b43c9f6367c37 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 謝辭 i
中文摘要 ii Abstract iii Contents v Introduction 1 Materials & Methods 7 Yeast Strains and Plasmids 7 Stress Resistance Experiments 8 Protein extraction and Immunoblotting 8 Selenomethionine Resistance Assay 9 Drug treatments and Antibodies 9 Co-immunoprecipitation Assay 10 RNA extraction and qRT-PCR 11 GFP microscopic analysis 12 Results 13 Searching for potential Ids2-dependent Hsc82 clients 13 sam1 showed functional defect and the same phenotype as ids2 mutants 14 Reduction of Sam1 expression level in ids2∆ mutant depends on neither mRNA level nor protein degradation 17 Direct physical interaction among Ids2, Hsc82, and Sam1 18 Foci formation of Sam1 under stationary conditions and ids2∆ strains 19 Discussion 21 The plasticity of co-chaperone dependence on clients in the HSP90 chaperone system 21 Reduction of Sam1 protein expression level is due to multiple factors 23 Deletion of sam1 leads to mitochondrial defects 24 Correlation between Sam1 and caloric restriction 25 Figures 27 Figure 1. Searching for potential Ids2-dependent Hsc82 clients 28 Figure 2. sam1 showed functional defect and the same phenotype as ids2 mutants under different stress conditions 31 Figure 3. Reduction of Sam1 expression level in ids2∆ mutant depends on neither mRNA level nor protein degradation. 33 Figure 4. Physical interactions between Sam1 and Ids2 or Hsc82. 34 Figure 5. Sam1-GFP forms foci at stationary phase and in ids2∆ strain under various conditions 36 Tables 37 Table 1. 15 potential clients of Ids2-Hsc82 complex 37 Table 2. Yeast strains and Plasmids used in this study 38 Table 3. Oligonucleotides used in this study 40 References 43 | |
| dc.language.iso | zh-TW | |
| dc.subject | 老化 | zh_TW |
| dc.subject | 輔助性熱休克蛋白 | zh_TW |
| dc.subject | 出芽酵母菌 | zh_TW |
| dc.subject | 熱休克蛋白 | zh_TW |
| dc.subject | 蛋白聚集 | zh_TW |
| dc.subject | chaperones | en |
| dc.subject | budding yeast | en |
| dc.subject | aging | en |
| dc.subject | protein aggregate | en |
| dc.subject | co-chaperones | en |
| dc.title | 篩選分子伴侶複合物Hsc82-Ids2的潛在受質 | zh_TW |
| dc.title | Screening for potential clients of the Hsc82-Ids2 chaperone complex | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林敬哲(Jing-Jer Lin),吳青錫(Ching-Shyi Wu) | |
| dc.subject.keyword | 出芽酵母菌,老化,熱休克蛋白,輔助性熱休克蛋白,蛋白聚集, | zh_TW |
| dc.subject.keyword | budding yeast,aging,chaperones,co-chaperones,protein aggregate, | en |
| dc.relation.page | 47 | |
| dc.identifier.doi | 10.6342/NTU201803644 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-15 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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