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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄧述諄 | |
dc.contributor.author | Yu-Han Lin | en |
dc.contributor.author | 林郁涵 | zh_TW |
dc.date.accessioned | 2021-06-08T02:05:29Z | - |
dc.date.copyright | 2016-02-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-02-04 | |
dc.identifier.citation | REFERENCES
Amberg, D.C., Burke, D.J., and Strathern, J.N. (2005). Methods in Yeast Genetics: A Cold Spring Harbor Laboratory Course Manual, 2005 Edition (Cold Spring). Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., et al. (2000). Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics 25, 25-29. Budhwar, R., Fang, G., and Hirsch, J.P. (2011). Kelch repeat proteins control yeast PKA activity in response to nutrient availability. Cell cycle 10, 767-770. Choi, K.M., Kwon, Y.Y., and Lee, C.K. (2013). Characterization of global gene expression during assurance of lifespan extension by caloric restriction in budding yeast. Experimental gerontology 48, 1455-1468. de Magalhaes, J.P., and Toussaint, O. (2004). GenAge: a genomic and proteomic network map of human ageing. FEBS letters 571, 243-247. Dennis, G., Jr., Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Lane, H.C., and Lempicki, R.A. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome biology 4, P3. Dilova, I., Easlon, E., and Lin, S.J. (2007). Calorie restriction and the nutrient sensing signaling pathways. Cellular and molecular life sciences : CMLS 64, 752-767. Engel, S.R., Balakrishnan, R., Binkley, G., Christie, K.R., Costanzo, M.C., Dwight, S.S., Fisk, D.G., Hirschman, J.E., Hitz, B.C., Hong, E.L., et al. (2010). Saccharomyces Genome Database provides mutant phenotype data. Nucleic acids research 38, D433-436. Fabrizio, P., and Longo, V.D. (2003). The chronological life span of Saccharomyces cerevisiae. Aging cell 2, 73-81. Fujioka, Y., Suzuki, S.W., Yamamoto, H., Kondo-Kakuta, C., Kimura, Y., Hirano, H., Akada, R., Inagaki, F., Ohsumi, Y., and Noda, N.N. (2014). Structural basis of starvation-induced assembly of the autophagy initiation complex. Nature structural & molecular biology 21, 513-521. Han, C.L., Chien, C.W., Chen, W.C., Chen, Y.R., Wu, C.P., Li, H., and Chen, Y.J. (2008). A multiplexed quantitative strategy for membrane proteomics: opportunities for mining therapeutic targets for autosomal dominant polycystic kidney disease. Molecular & cellular proteomics : MCP 7, 1983-1997. Kaeberlein, M. (2010). Lessons on longevity from budding yeast. Nature 464, 513-519. Kaeberlein, M., Powers, R.W., 3rd, Steffen, K.K., Westman, E.A., Hu, D., Dang, N., Kerr, E.O., Kirkland, K.T., Fields, S., and Kennedy, B.K. (2005). Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193-1196. Kenyon, C.J. (2010). The genetics of ageing. Nature 464, 504-512. Kettner, K., Krause, U., Mosler, S., Bodenstein, C., Kriegel, T.M., and Rodel, G. (2012). Saccharomyces cerevisiae gene YMR291W/TDA1 mediates the in vivo phosphorylation of hexokinase isoenzyme 2 at serine-15. FEBS letters 586, 455-458. Kriegel, T.M., Rush, J., Vojtek, A.B., Clifton, D., and Fraenkel, D.G. (1994). In vivo phosphorylation site of hexokinase 2 in Saccharomyces cerevisiae. Biochemistry 33, 148-152. Lin, S.J., Defossez, P.A., and Guarente, L. (2000). Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289, 2126-2128. Lin, S.S., Manchester, J.K., and Gordon, J.I. (2003). Sip2, an N-myristoylated beta subunit of Snf1 kinase, regulates aging in Saccharomyces cerevisiae by affecting cellular histone kinase activity, recombination at rDNA loci, and silencing. J Biol Chem 278, 13390-13397. Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., and Kroemer, G. (2013). The hallmarks of aging. Cell 153, 1194-1217. Lu, X., and Zhu, H. (2005). Tube-gel digestion: a novel proteomic approach for high throughput analysis of membrane proteins. Molecular & cellular proteomics : MCP 4, 1948-1958. Masoro, E.J. (2005). Overview of caloric restriction and ageing. Mechanisms of ageing and development 126, 913-922. Mattson, M.P., and Wan, R. (2005). Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. The Journal of nutritional biochemistry 16, 129-137. McCay, C.M., Crowell, M.F., and Maynard, L.A. (1935). The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size: One Figure. The Journal of nutrition 10, 63-79. Medvedik, O., Lamming, D.W., Kim, K.D., and Sinclair, D.A. (2007). MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS biology 5, e261. Mortimer, R.K., and Johnston, J.R. (1959). Life span of individual yeast cells. Nature 183, 1751-1752. Mostafavi, S., Ray, D., Warde-Farley, D., Grouios, C., and Morris, Q. (2008). GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. Genome biology 9 Suppl 1, S4. Partridge, L., and Mangel, M. (1999). Messages from mortality: the evolution of death rates in the old. Trends in ecology & evolution 14, 438-442. Roth, G.S., Ingram, D.K., and Lane, M.A. (2001). Caloric restriction in primates and relevance to humans. Annals of the New York Academy of Sciences 928, 305-315. Tsai, C.F., Wang, Y.T., Chen, Y.R., Lai, C.Y., Lin, P.Y., Pan, K.T., Chen, J.Y., Khoo, K.H., and Chen, Y.J. (2008). Immobilized metal affinity chromatography revisited: pH/acid control toward high selectivity in phosphoproteomics. Journal of proteome research 7, 4058-4069. Tsou, C.C., Tsai, C.F., Tsui, Y.H., Sudhir, P.R., Wang, Y.T., Chen, Y.J., Chen, J.Y., Sung, T.Y., and Hsu, W.L. (2010). IDEAL-Q, an automated tool for label-free quantitation analysis using an efficient peptide alignment approach and spectral data validation. Molecular & cellular proteomics : MCP 9, 131-144. Ullrich, A., and Schlessinger, J. (1990). Signal transduction by receptors with tyrosine kinase activity. Cell 61, 203-212. Wang, Y.T., Tsai, C.F., Hong, T.C., Tsou, C.C., Lin, P.Y., Pan, S.H., Hong, T.M., Yang, P.C., Sung, T.Y., Hsu, W.L., et al. (2010). An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. Journal of proteome research 9, 5582-5597. Warde-Farley, D., Donaldson, S.L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., Franz, M., Grouios, C., Kazi, F., Lopes, C.T., et al. (2010). The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic acids research 38, W214-220. Wei, M., Fabrizio, P., Hu, J., Ge, H., Cheng, C., Li, L., and Longo, V.D. (2008). Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS genetics 4, e13. Winzeler, E.A., Shoemaker, D.D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J.D., Bussey, H., et al. (1999). Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901-906. Zaman, S., Lippman, S.I., Zhao, X., and Broach, J.R. (2008). How Saccharomyces responds to nutrients. Annual review of genetics 42, 27-81. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19559 | - |
dc.description.abstract | 老化是一種細胞逐漸喪失生理功能的複雜過程,過去研究指出熱量限制能有效地延長各物種的平均壽命、延緩老化,其重要調控機制已被報導是藉由TOR/Sch9及 Ras/PKA等訊息傳遞路徑所調控,藉此適應外在環境營養的改變,延長細胞壽命,然而確切的調控機制目前還不清楚。由於熱量限制會影響許多磷酸化蛋白的訊息傳遞,所以我們想探討在熱量限制的酵母菌中是如何藉由磷酸化或去磷酸化來調控細胞的壽命。本篇研究分別將酵母菌培養在含有不同濃度葡萄糖(2%,0.5%)的培養基中,並用蛋白質體學分析找出可能是經由熱量限制導致磷酸化調控變異的蛋白。結果顯示在熱量限制的情況下,酵母菌有318個蛋白會被磷酸化,425個蛋白會被去磷酸化,接著利用Gene ontology及GeneMANIA的分析,並結合SGD phenotype,GeneAge資料庫,我們一共選擇了22個蛋白做後續的分析,透過單點或雙點點突變去模擬磷酸化狀態的改變,觀察在不同的壓力下其生長情形是否會被影響,結果顯示這些磷酸化位點皆不會影響到其功能,因此我們未來還需要做更進一步的分析。 | zh_TW |
dc.description.abstract | Aging often characterized as a complex process accompanied by progressive loss of physiological functions. Previous studies reveal that calorie restriction (CR) can effectively extend the lifespan of various organisms, delay the aging process. The critical mechanisms of CR have been reported by the regulation of TOR/Sch9 and Ras/PKA signaling pathways. While the exact mechanism still remains elusive, due to CR affecting many signaling pathways through phosphorylation, we aim to investigate how yeast cells mediate the lifespan by phosphorylation under CR. In this study, yeast cells were grown in medium containing 2% or 0.5% glucose, respectively. Then we employed the quantitative proteomics to elucidate which proteins may be regulated. There were 318 proteins been phosphorylated, and 425 proteins been dephosphorylated under CR. Next, we analyzed these proteins by Gene ontology and GeneMANIA, and combined with SGD phenotype and GeneAge database. In total, 22 candidates were selected for further investigation. By generating phospho-mimic or phospho-abolishing mutants to verify growth under different types of stress. Results showed that the single point or multiple site mutations did not affect the function of identified proteins. Consequently, further analysis are needed in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:05:29Z (GMT). No. of bitstreams: 1 ntu-105-R02445136-1.pdf: 985410 bytes, checksum: ac129bbbe2f42db5e8b73ff120c596c5 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 摘要. . . . . . . . . . . . . . . . . . . . . . . . . . i
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . ii CONTENTS . . . . . . . . . . . . . . . . . . . . . . iii INTRODUCTION . . . . . . . . . . . . . . . . . . . . . .1 MATERIALS & METHODS Yeast Strains and Plasmids . . . . . . . . . . . . . . 5 Samples Preparation . . . . . . . . . . . . . . . . . 5 LC-MS/MS Analysis . . . . . . . . . . . . . . . . . . .6 Bioinformatics Analysis - Gene Ontology Enrichment Analysis . . . . . . . . . . . . . . . . . .. . . . . . 8 Bioinformatics Analysis - GeneMANIA Analysis . . . . . 8 Stress Resistance Assay. . . . . . . . . . . . . . . . 9 RESULTS Identification of (de)Phosphorylated Proteins and Their Sites under Calorie Restriction. . . . . . . . . . . . 10 Identification of Novel Transcription Associated Candidates Based on GO analysis . . . . . . . . . . . .11 Verification of Transcription Associated Candidates through Measuring the Growth of Phospho-mimic or Phospho-abolishing Mutants . . . . . . . . . . . . . . . . . . 12 Identification of Novel Stress Response Associated Candidates . . . . . . . . . . . . . . . . . . . . . . 13 Verification of Stress Response Associated Candidates through Measuring the Growth of Phospho-mimic or Phospho-abolishing Mutants. . . . . . . . . . . . . . . . . . .14 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . 15 FIGURES . . . . . . . . . . . . . . . . . . . . . . . .16 Fig.1 Proteome analysis of S. cerevisiae under calorie restriction Fig.2 Top 20 Over-represented Gene Ontology (GO) Terms under Calorie Restriction Fig.3 Functional Categorization of Transcription Associated Genes Based on GO Analysis with GeneMANIA Fig.4 Growth of Single Point Mutants or Multiple-sites Mutation of Chosen Candidates Did Not Affect Their Functions TABLES. . . . . . . . . . . . . . . . . . . . . . . . .23 Table.1 Yeast Strains and Plasmids Used in This Study Table.2 Transcription Associated Candidates Selected in This Study Table.3 Sequencing Results of Pop-out Strains Table.4 Transcription Associated Candidates and the Stress Sensitivity Results Table.5 Stress Response Associated Candidates and the Stress Sensitivity Results REFERENCES. . . . . . . . . . . . . . . . . . . . . . .33 | |
dc.language.iso | en | |
dc.title | 總體的找出熱量限制時老化訊息傳遞路徑中的磷酸化位點與功能 | zh_TW |
dc.title | Global analysis of phosphorylation sites under calorie restriction to provide insights into signaling pathways in aging | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 李財坤,林敬哲 | |
dc.subject.keyword | 老化,熱量限制,磷酸化, | zh_TW |
dc.subject.keyword | aging,calorie restriction,phosphorylation, | en |
dc.relation.page | 38 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2016-02-04 | |
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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