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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李芳仁 | |
| dc.contributor.author | Yu-Chieh Wu | en |
| dc.contributor.author | 吳雨潔 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:52:51Z | - |
| dc.date.available | 2021-07-10T21:52:51Z | - |
| dc.date.copyright | 2019-08-28 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-14 | |
| dc.identifier.citation | Anania, V. G., D. J. Bustos, J. R. Lill, D. S. Kirkpatrick and L. Coscoy (2013). 'A Novel Peptide-Based SILAC Method to Identify the Posttranslational Modifications Provides Evidence for Unconventional Ubiquitination in the ER-Associated Degradation Pathway.' Int J Proteomics 2013: 857918.
Babour, A., A. A. Bicknell, J. Tourtellotte and M. Niwa (2010). 'A surveillance pathway monitors the fitness of the endoplasmic reticulum to control its inheritance.' Cell 142(2): 256-269. Back, S. H., M. Schroder, K. Lee, K. Zhang and R. J. Kaufman (2005). 'ER stress signaling by regulated splicing: IRE1/HAC1/XBP1.' Methods 35(4): 395-416. Behnia, R., B. Panic, J. R. Whyte and S. Munro (2004). 'Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p.' Nat Cell Biol 6(5): 405-413. Benyair, R., E. Ron and G. Z. Lederkremer (2011). 'Protein quality control, retention, and degradation at the endoplasmic reticulum.' Int Rev Cell Mol Biol 292: 197-280. Bigay, J., J. F. Casella, G. Drin, B. Mesmin and B. Antonny (2005). 'ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif.' Embo j 24(13): 2244-2253. Bigay, J., P. Gounon, S. Robineau and B. Antonny (2003). 'Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature.' Nature 426(6966): 563-566. Blader, I. J., M. J. Cope, T. R. Jackson, A. A. Profit, A. F. Greenwood, D. G. Drubin, G. D. Prestwich and A. B. Theibert (1999). 'GCS1, an Arf guanosine triphosphatase-activating protein in Saccharomyces cerevisiae, is required for normal actin cytoskeletal organization in vivo and stimulates actin polymerization in vitro.' Mol Biol Cell 10(3): 581-596. Broach, J. R. (2012). 'Nutritional control of growth and development in yeast.' Genetics 192(1): 73-105. Bruce Alberts, A. J., Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. (2008). Molecular Biology of the Cell. New York, Garland Science. Carling, D., K. Aguan, A. Woods, A. J. Verhoeven, R. K. Beri, C. H. Brennan, C. Sidebottom, M. D. Davison and J. Scott (1994). 'Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism.' J Biol Chem 269(15): 11442-11448. Chen, B., M. Retzlaff, T. Roos and J. Frydman (2011). 'Cellular strategies of protein quality control.' Cold Spring Harb Perspect Biol 3(8): a004374. Chen, K. Y., P. C. Tsai, J. W. Hsu, H. C. Hsu, C. Y. Fang, L. C. Chang, Y. T. Tsai, C. J. Yu and F. J. Lee (2010). 'Syt1p promotes activation of Arl1p at the late Golgi to recruit Imh1p.' J Cell Sci 123(Pt 20): 3478-3489. Chen, K. Y., P. C. Tsai, Y. W. Liu and F. J. Lee (2012). 'Competition between the golgin Imh1p and the GAP Gcs1p stabilizes activated Arl1p at the late-Golgi.' J Cell Sci 125(Pt 19): 4586-4596. Chen, L., Z. H. Jiao, L. S. Zheng, Y. Y. Zhang, S. T. Xie, Z. X. Wang and J. W. Wu (2009). 'Structural insight into the autoinhibition mechanism of AMP-activated protein kinase.' Nature 459(7250): 1146-1149. Chen, Y. and F. Brandizzi (2013). 'IRE1: ER stress sensor and cell fate executor.' Trends Cell Biol 23(11): 547-555. Chen, Y., D. E. Feldman, C. Deng, J. A. Brown, A. F. De Giacomo, A. F. Gaw, G. Shi, Q. T. Le, J. M. Brown and A. C. Koong (2005). 'Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae.' Mol Cancer Res 3(12): 669-677. Chen, Y. T., I. H. Wang, Y. H. Wang, W. Y. Chiu, J. H. Hu, W. H. Chen and F. S. Lee (2019). 'Action of Arl1 GTPase and golgin Imh1 in Ypt6-independent retrograde transport from endosomes to the trans-Golgi network.' Mol Biol Cell 30(8): 1008-1019. Connolly, J. E. and J. Engebrecht (2006). 'The Arf-GTPase-activating protein Gcs1p is essential for sporulation and regulates the phospholipase D Spo14p.' Eukaryot Cell 5(1): 112-124. Cooper, G. (2018). The Cell: A Molecular Approach, Sinauer Associates is an imprint of Oxford University Press. Cox, J. S., C. E. Shamu and P. Walter (1993). 'Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase.' Cell 73(6): 1197-1206. Cui, Y., Z. Yang and R. D. Teasdale (2018). 'The functional roles of retromer in Parkinson's disease.' FEBS Lett 592(7): 1096-1112. Cukierman, E., I. Huber, M. Rotman and D. Cassel (1995). 'The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex localization.' Science 270(5244): 1999-2002. Diehl, J. A., S. Y. Fuchs and C. Koumenis (2011). 'The cell biology of the unfolded protein response.' Gastroenterology 141(1): 38-41, 41.e31-32. Donaldson, J. G. and C. L. Jackson (2011). 'ARF family G proteins and their regulators: roles in membrane transport, development and disease.' Nat Rev Mol Cell Biol 12(6): 362-375. Drebot, M. A., G. C. Johnston and R. A. Singer (1987). 'A yeast mutant conditionally defective only for reentry into the mitotic cell cycle from stationary phase.' Proc Natl Acad Sci U S A 84(22): 7948-7952. Gancedo, J. M. (2001). 'Control of pseudohyphae formation in Saccharomyces cerevisiae.' FEMS Microbiol Rev 25(1): 107-123. Gietz, R. D. and R. H. Schiestl (2007). 'High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method.' Nat Protoc 2(1): 31-34. Gietz, R. D. and A. Sugino (1988). 'New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.' Gene 74(2): 527-534. Gillingham, A. K. and S. Munro (2007). 'The small G proteins of the Arf family and their regulators.' Annu Rev Cell Dev Biol 23: 579-611. Goldberg, J. (1999). 'Structural and functional analysis of the ARF1-ARFGAP complex reveals a role for coatomer in GTP hydrolysis.' Cell 96(6): 893-902. Gonneaud, A., C. Jones, N. Turgeon, D. Lévesque, C. Asselin, F. Boudreau and F.-M. Boisvert (2016). 'A SILAC-Based Method for Quantitative Proteomic Analysis of Intestinal Organoids.' Scientific Reports 6: 38195. Gorlich, D., S. Prehn, E. Hartmann, K. U. Kalies and T. A. Rapoport (1992). 'A mammalian homolog of SEC61p and SECYp is associated with ribosomes and nascent polypeptides during translocation.' Cell 71(3): 489-503. Gouw, M., S. Michael, H. Sámano-Sánchez, M. Kumar, A. Zeke, B. Lang, B. Bely, L. B. Chemes, N. E. Davey, Z. Deng, F. Diella, C.-M. Gürth, A.-K. Huber, S. Kleinsorg, L. S. Schlegel, N. Palopoli, K. V. Roey, B. Altenberg, A. Reményi, H. Dinkel and T. J. Gibson (2017). 'The eukaryotic linear motif resource – 2018 update.' Nucleic Acids Research 46(D1): D428-D434. Harvey Lodish, A. B., Chris A. Kaiser, Monty Krieger, Matthew P. Scott, Anthony Bretscher, Hidde Ploegh, Paul Matsudaira (2007). Molecular Cell Biology, W. H. Freeman. Hiltunen, J. K., A. M. Mursula, H. Rottensteiner, R. K. Wierenga, A. J. Kastaniotis and A. Gurvitz (2003). 'The biochemistry of peroxisomal beta-oxidation in the yeast Saccharomyces cerevisiae.' FEMS Microbiol Rev 27(1): 35-64. Hong, S. P. and M. Carlson (2007). 'Regulation of snf1 protein kinase in response to environmental stress.' J Biol Chem 282(23): 16838-16845. Hsu, J.-W., K.-J. Chen and F.-J. S. Lee (2015). 'Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain.' Nature Communications 6: 7840. Hsu, J. W., Z. J. Chen, Y. W. Liu and F. J. Lee (2014). 'Mechanism of action of the flippase Drs2p in modulating GTP hydrolysis of Arl1p.' J Cell Sci 127(Pt 12): 2615-2620. Hsu, J. W., P. H. Tang, I. H. Wang, C. L. Liu, W. H. Chen, P. C. Tsai, K. Y. Chen, K. J. Chen, C. J. Yu and F. J. Lee (2016). 'Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p.' Proc Natl Acad Sci U S A 113(12): E1683-1690. Huber, I., E. Cukierman, M. Rotman, T. Aoe, V. W. Hsu and D. Cassel (1998). 'Requirement for both the amino-terminal catalytic domain and a noncatalytic domain for in vivo activity of ADP-ribosylation factor GTPase-activating protein.' J Biol Chem 273(38): 24786-24791. James Morré, H. H. M. (1974). Dynamic Aspects of Plant infrastructure. London, New York, McGraw-Hill. Kahn, R. A., E. Bruford, H. Inoue, J. M. Logsdon, Jr., Z. Nie, R. T. Premont, P. A. Randazzo, M. Satake, A. B. Theibert, M. L. Zapp and D. Cassel (2008). 'Consensus nomenclature for the human ArfGAP domain-containing proteins.' J Cell Biol 182(6): 1039-1044. Karhumaa, K., B. Wu and M. C. Kielland-Brandt (2010). 'Conditions with high intracellular glucose inhibit sensing through glucose sensor Snf3 in Saccharomyces cerevisiae.' J Cell Biochem 110(4): 920-925. Krauss, G. (2008). Biochemistry of signal transduction and regulation, Wiley-VCH. LaGrassa, T. J. and C. Ungermann (2005). 'The vacuolar kinase Yck3 maintains organelle fragmentation by regulating the HOPS tethering complex.' J Cell Biol 168(3): 401-414. Lang, M. J., J. Y. Martinez-Marquez, D. C. Prosser, L. R. Ganser, D. Buelto, B. Wendland and M. C. Duncan (2014). 'Glucose starvation inhibits autophagy via vacuolar hydrolysis and induces plasma membrane internalization by down-regulating recycling.' J Biol Chem 289(24): 16736-16747. Lascaris, R., H. J. Bussemaker, A. Boorsma, M. Piper, H. van der Spek, L. Grivell and J. Blom (2003). 'Hap4p overexpression in glucose-grown Saccharomyces cerevisiae induces cells to enter a novel metabolic state.' Genome Biol 4(1): R3. Liu, W., R. Duden, R. D. Phair and J. Lippincott-Schwartz (2005). 'ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells.' J Cell Biol 168(7): 1053-1063. Liu, Y. W., C. F. Huang, K. B. Huang and F. J. Lee (2005). 'Role for Gcs1p in regulation of Arl1p at trans-Golgi compartments.' Mol Biol Cell 16(9): 4024-4033. Liu, Y. W., S. W. Lee and F. J. Lee (2006). 'Arl1p is involved in transport of the GPI-anchored protein Gas1p from the late Golgi to the plasma membrane.' J Cell Sci 119(Pt 18): 3845-3855. Manlandro, C. M., V. R. Palanivel, E. B. Schorr, N. Mihatov, A. A. Antony and A. G. Rosenwald (2012). 'Mon2 is a negative regulator of the monomeric G protein, Arl1.' FEMS Yeast Res 12(6): 637-650. Mitchelhill, K. I., D. Stapleton, G. Gao, C. House, B. Michell, F. Katsis, L. A. Witters and B. E. Kemp (1994). 'Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase.' J Biol Chem 269(4): 2361-2364. Möbius, K. (1884). 'Das Sterben der einzelligen und der vielzelligen Tiere.' Biologisches Centralblatt 4: 4. Momcilovic, M., S. H. Iram, Y. Liu and M. Carlson (2008). 'Roles of the glycogen-binding domain and Snf4 in glucose inhibition of SNF1 protein kinase.' J Biol Chem 283(28): 19521-19529. Moran, M. F., P. Polakis, F. McCormick, T. Pawson and C. Ellis (1991). 'Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein.' Mol Cell Biol 11(4): 1804-1812. Orlova, M., E. Kanter, D. Krakovich and S. Kuchin (2006). 'Nitrogen availability and TOR regulate the Snf1 protein kinase in Saccharomyces cerevisiae.' Eukaryot Cell 5(11): 1831-1837. Orlova, M., H. Ozcetin, L. Barrett and S. Kuchin (2010). 'Roles of the Snf1-activating kinases during nitrogen limitation and pseudohyphal differentiation in Saccharomyces cerevisiae.' Eukaryot Cell 9(1): 208-214. Orzechowski Westholm, J., S. Tronnersjo, N. Nordberg, I. Olsson, J. Komorowski and H. Ronne (2012). 'Gis1 and Rph1 regulate glycerol and acetate metabolism in glucose depleted yeast cells.' PLoS One 7(2): e31577. Palecek, S. P., A. S. Parikh and S. J. Kron (2002). 'Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth.' Microbiology 148(Pt 4): 893-907. Palomino, A., P. Herrero and F. Moreno (2006). 'Tpk3 and Snf1 protein kinases regulate Rgt1 association with Saccharomyces cerevisiae HXK2 promoter.' Nucleic Acids Res 34(5): 1427-1438. Panic, B., J. R. Whyte and S. Munro (2003). 'The ARF-like GTPases Arl1p and Arl3p act in a pathway that interacts with vesicle-tethering factors at the Golgi apparatus.' Curr Biol 13(5): 405-410. Pecheur, E. I., O. Maier and D. Hoekstra (2000). 'On the mechanism of intracellular membrane fusion: in search of the genuine fusion factor.' Biosci Rep 20(6): 613-631. Pedruzzi, I., F. Dubouloz, E. Cameroni, V. Wanke, J. Roosen, J. Winderickx and C. De Virgilio (2003). 'TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0.' Mol Cell 12(6): 1607-1613. Poon, P. P., S. F. Nothwehr, R. A. Singer and G. C. Johnston (2001). 'The Gcs1 and Age2 ArfGAP proteins provide overlapping essential function for transport from the yeast trans-Golgi network.' J Cell Biol 155(7): 1239-1250. Poon, P. P., X. Wang, M. Rotman, I. Huber, E. Cukierman, D. Cassel, R. A. Singer and G. C. Johnston (1996). 'Saccharomyces cerevisiae Gcs1 is an ADP-ribosylation factor GTPase-activating protein.' Proc Natl Acad Sci U S A 93(19): 10074-10077. Ptacek, J., G. Devgan, G. Michaud, H. Zhu, X. Zhu, J. Fasolo, H. Guo, G. Jona, A. Breitkreutz, R. Sopko, R. R. McCartney, M. C. Schmidt, N. Rachidi, S. J. Lee, A. S. Mah, L. Meng, M. J. Stark, D. F. Stern, C. De Virgilio, M. Tyers, B. Andrews, M. Gerstein, B. Schweitzer, P. F. Predki and M. Snyder (2005). 'Global analysis of protein phosphorylation in yeast.' Nature 438(7068): 679-684. Ratnakumar, S. and E. T. Young (2010). 'Snf1 dependence of peroxisomal gene expression is mediated by Adr1.' J Biol Chem 285(14): 10703-10714. Reitz, C. (2018). 'Retromer Dysfunction and Neurodegenerative Disease.' Curr Genomics 19(4): 279-288. Robertson, L. S. and G. R. Fink (1998). 'The three yeast A kinases have specific signaling functions in pseudohyphal growth.' Proc Natl Acad Sci U S A 95(23): 13783-13787. Robinson, M., P. P. Poon, C. Schindler, L. E. Murray, R. Kama, G. Gabriely, R. A. Singer, A. Spang, G. C. Johnston and J. E. Gerst (2006). 'The Gcs1 Arf-GAP mediates Snc1,2 v-SNARE retrieval to the Golgi in yeast.' Mol Biol Cell 17(4): 1845-1858. Schmidt, M. C. and R. R. McCartney (2000). 'beta-subunits of Snf1 kinase are required for kinase function and substrate definition.' Embo j 19(18): 4936-4943. Schroder, M. and R. J. Kaufman (2005). 'ER stress and the unfolded protein response.' Mutat Res 569(1-2): 29-63. Shirra, M. K., R. R. McCartney, C. Zhang, K. M. Shokat, M. C. Schmidt and K. M. Arndt (2008). 'A chemical genomics study identifies Snf1 as a repressor of GCN4 translation.' J Biol Chem 283(51): 35889-35898. Sikorska, N., L. Lemus, A. Aguilera-Romero, J. Manzano-Lopez, H. Riezman, M. Muniz and V. Goder (2016). 'Limited ER quality control for GPI-anchored proteins.' J Cell Biol 213(6): 693-704. Smith, A. (1997). Oxford dictionary of biochemistry and molecular biology. Oxford, Oxford University Press. Soulard, A., A. Cremonesi, S. Moes, F. Schutz, P. Jeno and M. N. Hall (2010). 'The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates.' Mol Biol Cell 21(19): 3475-3486. Stauffer, B. and T. Powers (2017). 'Target of rapamycin signaling mediates vacuolar fragmentation.' Curr Genet 63(1): 35-42. Stolz, A. and D. H. Wolf (2010). 'Endoplasmic reticulum associated protein degradation: a chaperone assisted journey to hell.' Biochim Biophys Acta 1803(6): 694-705. Surani, M. A. (1979). 'Glycoprotein synthesis and inhibition of glycosylation by tunicamycin in preimplantation mouse embryos: compaction and trophoblast adhesion.' Cell 18(1): 217-227. Swinnen, E., V. Wanke, J. Roosen, B. Smets, F. Dubouloz, I. Pedruzzi, E. Cameroni, C. De Virgilio and J. Winderickx (2006). 'Rim15 and the crossroads of nutrient signalling pathways in Saccharomyces cerevisiae.' Cell Div 1: 3. Tokarev, A. A., D. Taussig, G. Sundaram, Z. Lipatova, Y. Liang, J. W. Mulholland and N. Segev (2009). 'TRAPP II complex assembly requires Trs33 or Trs65.' Traffic 10(12): 1831-1844. Townley, R. and L. Shapiro (2007). 'Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase.' Science 315(5819): 1726-1729. Travers, K. J., C. K. Patil, L. Wodicka, D. J. Lockhart, J. S. Weissman and P. Walter (2000). 'Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation.' Cell 101(3): 249-258. Vida, T. A. and S. D. Emr (1995). 'A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast.' J Cell Biol 128(5): 779-792. Vincent, O., R. Townley, S. Kuchin and M. Carlson (2001). 'Subcellular localization of the Snf1 kinase is regulated by specific beta subunits and a novel glucose signaling mechanism.' Genes Dev 15(9): 1104-1114. Walkup, W. G. t., L. Washburn, M. J. Sweredoski, H. J. Carlisle, R. L. Graham, S. Hess and M. B. Kennedy (2015). 'Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases.' J Biol Chem 290(8): 4908-4927. Wang, X., M. F. Hoekstra, A. J. DeMaggio, N. Dhillon, A. Vancura, J. Kuret, G. C. Johnston and R. A. Singer (1996). 'Prenylated isoforms of yeast casein kinase I, including the novel Yck3p, suppress the gcs1 blockage of cell proliferation from stationary phase.' Mol Cell Biol 16(10): 5375-5385. Woods, A., M. R. Munday, J. Scott, X. Yang, M. Carlson and D. Carling (1994). 'Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo.' J Biol Chem 269(30): 19509-19515. Xu, C., B. Bailly-Maitre and J. C. Reed (2005). 'Endoplasmic reticulum stress: cell life and death decisions.' J Clin Invest 115(10): 2656-2664. Xu, P., R. D. Baldridge, R. J. Chi, C. G. Burd and T. R. Graham (2013). 'Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport.' J Cell Biol 202(6): 875-886. Xu, P., H. M. Hankins, C. MacDonald, S. J. Erlinger, M. N. Frazier, N. S. Diab, R. C. Piper, L. P. Jackson, J. A. MacGurn and T. R. Graham (2017). 'COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal.' Elife 6. Yoo, J., E. H. Mashalidis, A. C. Y. Kuk, K. Yamamoto, B. Kaeser, S. Ichikawa and S. Y. Lee (2018). 'GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation.' Nat Struct Mol Biol 25(3): 217-224. Young, E. T., K. M. Dombek, C. Tachibana and T. Ideker (2003). 'Multiple pathways are co-regulated by the protein kinase Snf1 and the transcription factors Adr1 and Cat8.' J Biol Chem 278(28): 26146-26158. Yu, C. J. and F. J. Lee (2017). 'Multiple activities of Arl1 GTPase in the trans-Golgi network.' J Cell Sci 130(10): 1691-1699. Zaman, S., S. I. Lippman, L. Schneper, N. Slonim and J. R. Broach (2009). 'Glucose regulates transcription in yeast through a network of signaling pathways.' Mol Syst Biol 5: 245. Zendeh-boodi, Z., T. Yamamoto, H. Sakane and K. Tanaka (2013). 'Identification of a second amphipathic lipid-packing sensor-like motif that contributes to Gcs1p function in the early endosome-to-TGN pathway.' The Journal of Biochemistry 153(6): 573-587. Zhang, C. J., M. M. Cavenagh and R. A. Kahn (1998). 'A family of Arf effectors defined as suppressors of the loss of Arf function in the yeast Saccharomyces cerevisiae.' J Biol Chem 273(31): 19792-19796. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77253 | - |
| dc.description.abstract | 腺嘌呤核苷二磷酸核糖化因子(Arfs)與腺嘌呤核苷二磷酸核糖化相似因子(Arls)被認為在囊泡運輸中扮演著重要的角色。在釀酒酵母菌中，第一腺嘌呤核苷二磷酸核糖化相似因子(Arl1)的鳥嘌呤核苷酸結合循環是由鳥嘌呤核苷酸交換因子(GEF) Syt1以及GTP酶活化蛋白(GAP) Gcs1進行轉換。然而，Gcs1接觸高基氏體並促進Arl1的GTP水解是如何受到調控的詳細機制仍然不清楚。在這裡，我們發現低水平的葡萄糖會誘發Gcs1的磷酸化。被質譜儀辨認到的那些磷酸化位點能調降Gcs1對於Arl1的GAP活性。再者，我們注意到Snf1與Rim15兩者所調節的路徑，在葡萄糖剝奪的環境中，都有助於Gcs1的磷酸化。此外，我們也演示了Gcs1在衣黴素處理後所導致的內質網壓力下會被磷酸化。藉由質譜儀，我們在Gcs1上鑑定到幾個對內質網壓力反應的新磷酸化位點，包含S157，T161，S321以及S322。我們觀察到被磷酸化的Gcs1能幫助Arl1與Imh1在未折疊蛋白質反應下進一步的募集到高基氏體。有趣的是，我們發現Gcs1在內質網壓力下磷酸化的引信並不依賴Ire1-Hac1這條為人熟知的訊息傳遞路徑，反而是經由Slt2相關的信號。並且，剔除Slt2減緩了在未折疊蛋白質反應下Imh1募集量的增加。因此，我們推測Gcs1磷酸化在空間與時間上的調節可能控制了Arl1在高基氏體上的活化狀態。 | zh_TW |
| dc.description.abstract | ADP-ribosylation factors (Arfs) and Arf-like proteins (Arls) are known to play critical roles in vesicle trafficking. In Saccharomyces cerevisiae, the guanine nucleotide-binding cycle of Arl1 is converted by the guanine nucleotide exchange factor (GEF), Syt1, and the GTPase activating protein (GAP), Gcs1. However, the detailed mechanism of how Gcs1 is regulated to access the Golgi membrane and promote GTP-hydrolysis of Arl1 remains unclear. Here, we find that the low level of glucose triggers Gcs1 phosphorylation. These phosphorylation sites recognized by mass spectrometry down-regulate the GAP activity of Gcs1 toward Arl1. Moreover, we notice that both the Snf1 and the Rim15 mediated pathways contribute to Gcs1 phosphorylation under glucose deprivation. Besides, we also demonstrate that Gcs1 is phosphorylated upon tunicamycin treatment, which causes ER stress. By mass spectrometry, we identify several new phosphorylation sites on Gcs1 in response to ER stress, including S157, T161, S321, and S322. We observe that the phosphorylated Gcs1 supports the further recruitment of Arl1 and Imh1 to Golgi upon UPR. Interestingly, we find that the trigger of Gcs1 phosphorylation upon ER stress was not dependent on a well-known Ire1-Hac1 signaling pathway, but rather Slt2 related signaling. Furthermore, Slt2 deletion attenuates the increase of Imh1 recruitment upon UPR. Thus, we infer that the spatial and temporal regulation of Gcs1 phosphorylation may modulate the activation status of Arl1 at the Golgi. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:52:51Z (GMT). No. of bitstreams: 1 ntu-108-R06448008-1.pdf: 13065682 bytes, checksum: 9b32e6fbeb188da3bb5119ba52a0dc2b (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii ABSTRACT iii CONTENTS v LIST OF FIGURES viii LIST OF TABLES x Chapter 1 Introduction 1 1.1 Arf-like proteins and vesicle trafficking 2 1.2 GTPase-activating proteins 3 1.3 Glucose deprivation 5 1.4 ER stress 8 Chapter 2 Material and Methods 11 2.1 Yeast strains, plasmids, and transformation 11 2.2 Media and culture conditions 11 2.3 Microscopy 12 2.4 Yeast protein extraction 12 2.5 Western blot 13 2.6 Plating assay 14 2.7 FM4-64 labeling 14 2.8 Fractionation 15 2.9 Mass spectrometry 16 2.10 Statistical analysis 17 Chapter 3 Results 18 3.1 Glucose deprivation triggered Gcs1 phosphorylation 18 3.1.1 Glucose deprivation induced Gcs1 phosphorylation and mislocalization of certain proteins 18 3.1.2 Phosphorylation caused a negative regulatory effect on Gcs1 GAP activity to some degree 19 3.1.3 No obvious phenotypic differences were found in between phosphor-deficient and mimetic mutants of Gcs1 except hygromycin B sensitivity 22 3.1.4 There were other pathways rather than Gcs1 contributing to the dispersed pattern of Arl1 under glucose deprivation 25 3.1.5 Snf1 and Rim15 served as putative kinases for Gcs1 whereas Tor1 played as a negative regulator 26 3.1.6 Snf1 or Rim15 deletion restored the mislocalization of Arl1 and Imh1 under glucose deprivation 27 3.1.7 Summary of the effects of glucose deprivation on Gcs1 27 3.2 Tunicamycin triggered Gcs1 phosphorylation 28 3.2.1 Gcs1 was phosphorylated under Tunicamycin treatment 28 3.2.2 Gcs1 showed cytosolic relocation under Tunicamycin treatment 29 3.2.3 Putative phosphorylation sites on Gcs1 triggered by Tunicamycin were identified by mass spectrometry 29 3.2.4 Mislocalization of Gcs1 under Tunicamycin treatment might be dependent on phosphorylation 30 3.2.5 Gcs1 phosphorylation contributed to the recruitment of Arl1 and Imh1 upon ER stress 31 3.2.6 Gcs1 phosphorylation was triggered by Slt2 related signaling rather than Ire1-Hac1 pathway 32 3.2.7 Summary of the spatial and temporal control of Gcs1 toward Arl1 inactivation upon ER stress 33 Chapter 4 Discussion 34 4.1 The stress responded phosphorylation on the site S157 and the site T161 of Gcs1 34 4.2 The strategies for identifying the phenotypes mediated by phosphorylated Gcs1 34 4.3 The signal pathways regulating Gcs1 phosphorylation 36 4.4 The possible mechanism of Arl1 mislocalization upon glucose deprivation 36 4.5 The crosstalk between nutrient sensing and trafficking 37 4.6 The possible mechanism of Gcs1 regulated Arl1 recruitment to Golgi upon ER stress 38 4.7 The crosstalk between ER stress response and trafficking 39 REFERENCES 86 | |
| dc.language.iso | en | |
| dc.subject | GTP?活化蛋白 | zh_TW |
| dc.subject | 內質網壓力 | zh_TW |
| dc.subject | 第一腺嘌呤核?二磷酸核糖化相似因子 | zh_TW |
| dc.subject | 磷酸化 | zh_TW |
| dc.subject | 葡萄糖剝奪 | zh_TW |
| dc.subject | glucose deprivation | en |
| dc.subject | Gcs1 | en |
| dc.subject | Arl1 | en |
| dc.subject | Imh1 | en |
| dc.subject | phosphorylation | en |
| dc.subject | glucose deprivation | en |
| dc.subject | ER stress | en |
| dc.subject | Gcs1 | en |
| dc.subject | Arl1 | en |
| dc.subject | Imh1 | en |
| dc.subject | phosphorylation | en |
| dc.subject | ER stress | en |
| dc.title | 探討磷酸化對於GTP酶活化蛋白Gcs1之影響 | zh_TW |
| dc.title | Characterization of the effects of phosphorylation on GTPase-activating protein Gcs1 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林敬哲,鄧述諄,王昭雯,陳瑞華 | |
| dc.subject.keyword | GTP?活化蛋白,第一腺嘌呤核?二磷酸核糖化相似因子,磷酸化,葡萄糖剝奪,內質網壓力, | zh_TW |
| dc.subject.keyword | Gcs1,Arl1,Imh1,phosphorylation,glucose deprivation,ER stress, | en |
| dc.relation.page | 100 | |
| dc.identifier.doi | 10.6342/NTU201903096 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2019-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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