Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95726Full metadata record
| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 宋麗英 | zh_TW |
| dc.contributor.advisor | Li-Ying Sung | en |
| dc.contributor.author | 彭敏 | zh_TW |
| dc.contributor.author | Min Peng | en |
| dc.date.accessioned | 2024-09-15T17:01:09Z | - |
| dc.date.available | 2024-09-16 | - |
| dc.date.copyright | 2024-09-15 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-06 | - |
| dc.identifier.citation | 1. Rustom, A., et al. (2004) Nanotubular highways for intercellular organelle transport. Science 303, 1007-1010.
2. Sheth, U. and Parker, R. (2006) Targeting of aberrant mRNAs to cytoplasmic processing bodies. Cell 125, 1095-1109. 3. An, S., et al. (2008) Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 320, 103-106. 4. Zhao, H., et al. (2013) The purinosome, a multi-protein complex involved in the de novo biosynthesis of purines in humans. Chem Commun (Camb) 49, 4444-4452. 5. Ingerson-Mahar, M., et al. (2010) The metabolic enzyme CTP synthase forms cytoskeletal filaments. Nat Cell Biol 12, 739-746. 6. Liu, J. L. (2010) Intracellular compartmentation of CTP synthase in Drosophila. J Genet Genomics 37, 281-296. 7. Noree, C., et al. (2010) Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster. J Cell Biol 190, 541-551. 8. Carcamo, W. C., et al. (2011) Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells. PLoS One 6, e29690. 9. Chen, K., et al. (2011) Glutamine analogs promote cytoophidium assembly in human and Drosophila cells. J Genet Genomics 38, 391-402. 10. Chang, C. C., et al. (2015) Cytoophidium assembly reflects upregulation of IMPDH activity. J Cell Sci 128, 3550-3555. 11. Keppeke, G. D., et al. (2015) Assembly of IMPDH2-based, CTPS-based, and mixed rod/ring structures is dependent on cell type and conditions of induction. J Genet Genomics 42, 287-299. 12. Chang, C. C., et al. (2018) Interfilament interaction between IMPDH and CTPS cytoophidia. FFEBS J 285, 3753-3768. 13. Narayanaswamy, R., et al. (2009) Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation. Proc Natl Acad Sci U S A 106, 10147-10152. 14. Shen, Q. J., et al. (2016) Filamentation of metabolic enzymes in Saccharomyces cerevisiae. J Genet Genomics 43, 393-404. 15. Chang, C. C., et al. (2022) Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation. Cell Mol Life Sci 79, 420. 16. Chang, C. C., et al. (2017) CTP synthase forms the cytoophidium in human hepatocellular carcinoma. Exp Cell Res 361, 292-299. 17. Lynch, E. M., et al. (2017) Human CTP synthase filament structure reveals the active enzyme conformation. Nat Struct Mol Biol 24, 507-514. 18. Calise, S. J., et al. (2018) Immune response-dependent assembly of IMP dehydrogenase filaments. Front Immunol 9, 2789. 19. Duong-Ly, K. C., et al. (2018) T cell activation triggers reversible inosine-5'-monophosphate dehydrogenase assembly. J Cell Sci 131, jcs223289. 20. Keppeke, G. D., et al. (2018) IMP/GTP balance modulates cytoophidium assembly and IMPDH activity. Cell Div 13, 5. 21. Sun, Z. and Liu, J. L. (2019) Forming cytoophidia prolongs the half-life of CTP synthase. Cell Discov 5, 32. 22. Pedley, A. M. and Benkovic, S. J. (2017) A new view into the regulation of purine metabolism: the purinosome. Trends Biochem Sci 42, 141-154. 23. Kofuji, S., et al. (2019) IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma. Nat Cell Biol 21, 1003-1014. 24. Jackson, R. C., et al. (1975) IMP dehydrogenase, an enzyme linked with proliferation and malignancy. Nature 256, 331-333. 25. Nagai, M., et al. (1991) Selective up-regulation of type II inosine 5'-monophosphate dehydrogenase messenger RNA expression in human leukemias. Cancer Res 51, 3886-3890. 26. He, Y., et al. (2009) Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis. Int J Colorectal Dis 24, 1271-1279. 27. Zhou, L., et al. (2014) Enhanced expression of IMPDH2 promotes metastasis and advanced tumor progression in patients with prostate cancer. Clin Transl Oncol 16, 906-913. 28. Zou, J., et al. (2015) Elevated expression of IMPDH2 is associated with progression of kidney and bladder cancer. Med Oncol 32, 373. 29. Xu, Y., et al. (2017) High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma. Sci Rep 7, 745. 30. Duan, S., et al. (2018) IMPDH2 promotes colorectal cancer progression through activation of the PI3K/AKT/mTOR and PI3K/AKT/FOXO1 signaling pathways. J Exp Clin Cancer Res 37, 304. 31. Huang, F., et al. (2018) Inosine monophosphate dehydrogenase dependence in a subset of small cell lung cancers. Cell Metab 28, 369-382.e365. 32. Allison, A. C. and Eugui, E. M. (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47, 85-118. 33. Hedstrom, L. (2009) IMP dehydrogenase: structure, mechanism, and inhibition. Chem Rev 109, 2903-2928. 34. Natsumeda, Y., et al. (1990) Two distinct cDNAs for human IMP dehydrogenase. J Biol Chem 265, 5292-5295. 35. Carr, S. F., et al. (1993) Characterization of human type I and type II IMP dehydrogenases. J Biol Chem 268, 27286-27290. 36. Senda, M. and Natsumeda, Y. (1994) Tissue-differential expression of two distinct genes for human IMP dehydrogenase (E.C.1.1.1.205). Life Sci 54, 1917-1926. 37. Jain, J., et al. (2004) Regulation of inosine monophosphate dehydrogenase type I and type II isoforms in human lymphocytes. Biochem Pharmacol 67, 767-776. 38. Bowne, S. J., et al. (2006) Why do mutations in the ubiquitously expressed housekeeping gene IMPDH1 cause retina-specific photoreceptor degeneration? Invest Ophthalmol Vis Sci 47, 3754-3765. 39. Gu, J. J., et al. (2000) Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH II gene. J Clin Invest 106, 599-606. 40. Gu, J. J., et al. (2003) Targeted disruption of the inosine 5'-monophosphate dehydrogenase type I gene in mice. Mol Cell Biol 23, 6702-6712. 41. Aherne, A., et al. (2004) On the molecular pathology of neurodegeneration in IMPDH1-based retinitis pigmentosa. Hum Mol Genet 13, 641-650. 42. Ji, Y., et al. (2006) Regulation of the interaction of inosine monophosphate dehydrogenase with mycophenolic acid by GTP. J Biol Chem 281, 206-212. 43. Calise, S. J., et al. (2016) 'Rod and ring' formation from IMP dehydrogenase is regulated through the one-carbon metabolic pathway. J Cell Sci 129, 3042-3052. 44. Juda, P., et al. (2014) Ultrastructure of cytoplasmic and nuclear inosine-5'-monophosphate dehydrogenase 2 "rods and rings" inclusions. J Histochem Cytochem 62, 739-750. 45. Anthony, S. A., et al. (2017) Reconstituted IMPDH polymers accommodate both catalytically active and inactive conformations. Mol Biol Cell 28, 2600-2608. 46. Johnson, M. C. and Kollman, J. M. (2020) Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation. Elife 9, e53243. 47. Plana-Bonamaisó, A., et al. (2020) Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions. Elife 9, e56418. 48. Peng, M., et al. (2021) CTPS and IMPDH form cytoophidia in developmental thymocytes. Exp Cell Res 405, 112662. 49. Zhou, X. L., et al. (2021) Inosine 5’-monophosphate dehydrogenase cytoophidia neighbor insulin granules in pancreatic β cells. Pancreas 50, e62-e64. 50. Metz, S. A., et al. (1992) Selective inhibitors of GTP synthesis impede exocytotic insulin release from intact rat islets. J Biol Chem 267, 12517-12527. 51. Kowluru, A., et al. (1996) Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure beta cells. Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion. J Clin Invest 98, 540-555. 52. Ciofani, M. and Zúñiga-Pflücker, J. C. (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6, 881-888. 53. Fayard, E., et al. (2007) Deletion of PKBalpha/Akt1 affects thymic development. PLoS One 2, e992. 54. Mao, C., et al. (2007) Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. J Immunol 178, 5443-5453. 55. Juntilla, M. M. and Koretzky, G. A. (2008) Critical roles of the PI3K/Akt signaling pathway in T cell development. Immunol Lett 116, 104-110. 56. Fayard, E., et al. (2010) Phosphatidylinositol 3-kinase signaling in thymocytes: the need for stringent control. Sci Signal 3, re5. 57. Finlay, D. K. (2012) Regulation of glucose metabolism in T cells: new insight into the role of Phosphoinositide 3-kinases. Front Immunol 3, 247. 58. Yang, K., et al. (2018) Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells. Sci Immunol 3, eaas9818. 59. Warburg, O. (1956) On the origin of cancer cells. Science 123, 309-314. 60. Hume, D. A. and Weidemann, M. J. (1979) Role and regulation of glucose metabolism in proliferating cells. J Natl Cancer Inst 62, 3-8. 61. Vander Heiden, M. G., et al. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033. 62. DeBerardinis, R. J., et al. (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7, 11-20. 63. Locasale, J. W. and Cantley, L. C. (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metab 14, 443-451. 64. Maschek, G., et al. (2004) 2-deoxy-d-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. Cancer Res 64, 31-34. 65. Prasanna, V. K., et al. (2009) Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma. J Cancer Res Ther 5 Suppl 1, S44-47. 66. Kondoh, H., et al. (2007) A high glycolytic flux supports the proliferative potential of murine embryonic stem cells. Antioxid Redox Signal 9, 293-299. 67. Folmes, C. D., et al. (2011) Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab 14, 264-271. 68. Varum, S., et al. (2011) Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One 6, e20914. 69. Zhang, J., et al. (2012) Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal. Cell Stem Cell 11, 589-595. 70. Rodrigues, A. S., et al. (2015) Differentiate or die: 3-bromopyruvate and pluripotency in mouse embryonic stem cells. PLoS One 10, e0135617. 71. Panopoulos, A. D., et al. (2012) The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res 22, 168-177. 72. Hansson, J., et al. (2012) Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. Cell Rep 2, 1579-1592. 73. Mathieu, J., et al. (2014) Hypoxia-inducible factors have distinct and stage-specific roles during reprogramming of human cells to pluripotency. Cell Stem Cell 14, 592-605. 74. Prigione, A., et al. (2014) HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2. Stem Cells 32, 364-376. 75. Prigione, A., et al. (2010) The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28, 721-733. 76. Folmes, C. D., et al. (2012) Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell 11, 596-606. 77. Biggers, J. D., et al. (1967) The pattern of energy metabolism in the mouse oöcyte and zygote. Proc Natl Acad Sci U S A 58, 560-567. 78. Leese, H. J. and Barton, A. M. (1984) Pyruvate and glucose uptake by mouse ova and preimplantation embryos. J Reprod Fertil 72, 9-13. 79. Lane, M. and Gardner, D. K. (2000) Lactate regulates pyruvate uptake and metabolism in the preimplantation mouse embryo. Biol Reprod 62, 16-22. 80. Chi, F., et al. (2020) Glycolysis-independent glucose metabolism distinguishes TE from ICM fate during mammalian embryogenesis. Dev Cell 53, 9-26.e24. 81. Sharpley, M. S., et al. (2021) Metabolic plasticity drives development during mammalian embryogenesis. Dev Cell 56, 2329-2347.e2326. 82. Li, J., et al. (2022) Metabolic control of histone acetylation for precise and timely regulation of minor ZGA in early mammalian embryos. Cell Discov 8, 96. 83. Ni, S., et al. (2021) Coordinated formation of IMPDH2 cytoophidium in mouse oocytes and granulosa cells. Front Cell Dev Biol 9, 690536. 84. Johnson, M. T., et al. (2003) Intermediary metabolism and energetics during murine early embryogenesis. J Biol Chem 278, 31457-31460. 85. Lu, C. and Thompson, C. B. (2012) Metabolic regulation of epigenetics. Cell Metab 16, 9-17. 86. Bulusu, V., et al. (2017) Spatiotemporal analysis of a glycolytic activity gradient linked to mouse embryo mesoderm development. Dev Cell 40, 331-341.e334. 87. Oginuma, M., et al. (2017) A gradient of glycolytic activity coordinates FGF and Wnt signaling during elongation of the body axis in amniote embryos. Dev Cell 40, 342-353.e310. 88. Solmonson, A., et al. (2022) Compartmentalized metabolism supports midgestation mammalian development. Nature 604, 349-353. 89. Calise, S. J., et al. (2014) Glutamine deprivation initiates reversible assembly of mammalian rods and rings. Cell Mol Life Sci 71, 2963-2973. 90. Gou, K. M., et al. (2014) CTP synthase forms cytoophidia in the cytoplasm and nucleus. Exp Cell Res 323, 242-253. 91. Keppeke, G. D., et al. (2019) IMP dehydrogenase rod/ring structures in acral melanomas. Pigment Cell Melanoma Res 33, 490-497. 92. Villa, E., et al. (2019) Cancer cells tune the signaling pathways to empower de novo synthesis of nucleotides. Cancers (Basel) 11, 688. 93. Masi, A., et al. (2021) The pentose phosphate pathway in industrially relevant fungi: crucial insights for bioprocessing. Appl Microbiol Biotechnol 105, 4017-4031. 94. Chen, W. and Guéron, M. (1992) The inhibition of bovine heart hexokinase by 2-deoxy-D-glucose-6-phosphate: characterization by 31P NMR and metabolic implications. Biochimie 74, 867-873. 95. Tyson, R. L., et al. (2000) 6-Aminonicotinamide inhibition of the pentose phosphate pathway in rat neocortex. Neuroreport 11, 1845-1848. 96. Kim, D. H., et al. (2015) Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming. Cell Stem Cell 16, 88-101. 97. Chung, S., et al. (2010) Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation. J Mol Cell Cardiol 48, 725-734. 98. Leese, H. J. (2012) Metabolism of the preimplantation embryo: 40 years on. Reproduction 143, 417-427. 99. Feng, J., et al. (2020) Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma. J Exp Clin Cancer Res 39, 126. 100. Thion, M. S., et al. (2018) Microglia and early brain development: An intimate journey. Science 362, 185-189. 101. Elmaci, İ., et al. (2018) Phosphorylated histone H3 (PHH3) as a novel cell proliferation marker and prognosticator for meningeal tumors: a short review. Appl Immunohistochem Mol Morphol 26, 627-631. 102. Elstrom, R. L., et al. (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64, 3892-3899. 103. Yu, Y., et al. (2014) Stimulation of somatic cell reprogramming by ERas-Akt-FoxO1 signaling axis. Stem Cells 32, 349-363. 104. Lane, M. and Gardner, D. K. (1998) Amino acids and vitamins prevent culture-induced metabolic perturbations and associated loss of viability of mouse blastocysts. Hum Reprod 13, 991-997. 105. Gaudelli, N. M., et al. (2017) Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464-471. 106. Liu, Z., et al. (2018) Highly efficient RNA-guided base editing in rabbit. Nat Commun 9, 2717. 107. Ryu, S. M., et al. (2018) Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy. Nat Biotechnol 36, 536-539. 108. Paling, N. R., et al. (2004) Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling. J Biol Chem 279, 48063-48070. 109. Kingham, E. and Welham, M. (2009) Distinct roles for isoforms of the catalytic subunit of class-IA PI3K in the regulation of behaviour of murine embryonic stem cells. J Cell Sci 122, 2311-2321. 110. Singh, A. M., et al. (2012) Signaling network crosstalk in human pluripotent cells: a Smad2/3-regulated switch that controls the balance between self-renewal and differentiation. Cell Stem Cell 10, 312-326. 111. Messina, E., et al. (2004) Guanine nucleotide depletion triggers cell cycle arrest and apoptosis in human neuroblastoma cell lines. Int J Cancer 108, 812-817. 112. Singh, A., et al. (2022) Cellular experiments to study the inhibition of c-Myc/MAX heterodimerization. Methods Enzymol 675, 193-205. 113. Qvarnström, O. F., et al. (2009) γH2AX and cleaved PARP-1 as apoptotic markers in irradiated breast cancer BT474 cellular spheroids. Int J Oncol 35, 41-47. 114. Wen, W., et al. (2010) MST1 promotes apoptosis through phosphorylation of histone H2AX. J Biol Chem 285, 39108-39116. 115. Wang, Z. Q., et al. (1997) Generation of completely embryonic stem cell-derived mutant mice using tetraploid blastocyst injection. Mech Dev 62, 137-145. 116. Kress, T. R., et al. (2015) MYC: connecting selective transcriptional control to global RNA production. Nat Rev Cancer 15, 593-607. 117. Swamy, M., et al. (2016) Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. Nat Immunol 17, 712-720. 118. Gabriel, S. S. and Kallies, A. (2016) Glucose- and glutamine-fueled stabilization of C-Myc is required for T-cell proliferation and malignant transformation. Cell Death Discov 2, 16047. 119. Grandori, C., et al. (2005) c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7, 311-318. 120. Kim, S., et al. (2000) Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo. Proc Natl Acad Sci U S A 97, 11198-11202. 121. Nguyen le, X. T., et al. (2015) Regulation of ribosomal RNA synthesis in T cells: requirement for GTP and Ebp1. Blood 125, 2519-2529. 122. Ahangari, N., et al. (2021) Nuclear IMPDH filaments in human gliomas. J Neuropathol Exp Neurol 80, 944-954. 123. Worldwide cancer data. (2022) World Cancer Research Fund International https://www.wcrf.org/cancer-trends/worldwide-cancer-data/ 124. Keppeke, G. D., et al. (2016) Differential capacity of therapeutic drugs to induce Rods/Rings structures in vitro and in vivo and generation of anti-Rods/Rings autoantibodies. Clin Immunol 173, 149-156. 125. Keppeke, G. D., et al. (2021) IMPDH forms the cytoophidium in zebrafish. Dev Biol 478, 89-101. 126. Valvezan, A. J., et al. (2017) mTORC1 couples nucleotide synthesis to nucleotide demand resulting in a targetable metabolic vulnerability. Cancer Cell 32, 624-638.e625. 127. Wang, X., et al. (2017) Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Nat Neurosci 20, 661-673. 128. Carter, S. B., et al. (1969) Mycophenolic acid: an anti-cancer compound with unusual properties. Nature 223, 848-850. 129. Williams, R. H., et al. (1968) Mycophenolic acid: antiviral and antitumor properties. J Antibiot (Tokyo) 21, 463-464. 130. Suzuki, S., et al. (1969) Antitumor activity of mycophenolic acid. 22, 297-302. 131. Suzuki, S., et al. (1976) Antitumor activity of derivatives of mycophenolic acid. J Antibiot (Tokyo) 29, 275-285. 132. Tressler, R. J., et al. (1994) Anti-tumor activity of mycophenolate mofetil against human and mouse tumors in vivo. Int J Cancer 57, 568-573. 133. Carcamo, W. C., et al. (2014) Molecular cell biology and immunobiology of mammalian rod/ring structures. Int Rev Cell Mol Biol 308, 35-74. 134. Noree, C., et al. (2019) A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network. Mol Biol Cell 30, 2721-2736. 135. Munyon, W. H. and Merchant, D. J. (1959) The relation between glucose utilization, lactic acid production and utilization and the growth cycle of L strain fibroblasts. Exp Cell Res 17, 490-498. 136. Hedeskov, C. J. (1968) Early effects of phytohaemagglutinin on glucose metabolism of normal human lymphocytes. Biochem J 110, 373-380. 137. Wang, T., et al. (1976) Aerobic glycolysis during lymphocyte proliferation. Nature 261, 702-705. 138. Hume, D. A., et al. (1978) Aerobic glycolysis and lymphocyte transformation. Biochem J 174, 703-709. 139. Brand, K. (1985) Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism. Biochem J 228, 353-361. 140. Burrell, A. L., et al. (2022) IMPDH1 retinal variants control filament architecture to tune allosteric regulation. Nat Struct Mol Biol 29, 47-58. 141. Chen, H., et al. (2018) Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther 3, 5. 142. Dang, C. V. (2012) MYC on the path to cancer. Cell 149, 22-35. 143. Kim, J. W., et al. (2004) Evaluation of myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Mol Cell Biol 24, 5923-5936. 144. Liu, Y. C., et al. (2008) Global regulation of nucleotide biosynthetic genes by c-Myc. PLoS One 3, e2722. 145. Mannava, S., et al. (2008) Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle 7, 2392-2400. 146. Barfeld, S. J., et al. (2015) Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer. Oncotarget 6, 12587-12602. 147. Kofuji, S. and Sasaki, A. T. (2020) GTP metabolic reprogramming by IMPDH2: unlocking cancer cells' fuelling mechanism. J Biochem 168, 319-328. 148. Huang, F., et al. (2021) Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer. J Clin Invest 131, e139929. 149. Zhang, Q., et al. (2023) c-Myc-IMPDH1/2 axis promotes tumourigenesis by regulating GTP metabolic reprogramming. Clin Transl Med 13, e1164. 150. Cornuel, J.-F., et al. (2002) Participation of yeast inosine 5'-monophosphate dehydrogenase in an in vitro complex with a fragment of the C-rich telomeric strand. 84, 279-289. 151. McLean, J. E., et al. (2004) Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo. 379, 243-251. 152. Kozhevnikova, E. N., et al. (2012) Metabolic enzyme IMPDH is also a transcription factor regulated by cellular state. Mol Cell 47, 133-139. 153. Moussaieff, A., et al. (2015) Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab 21, 392-402. 154. Xu, W., et al. (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19, 17-30. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95726 | - |
| dc.description.abstract | 細胞蛇 (cytoophidium) 為細胞中由代謝酶多聚體聚合形成之新型無膜細胞器，可能調控組成代謝酶之活性、穩定度等特性。肌苷酸脫氫酶 (inosine monophosphate dehydrogenase, IMPDH) 負責催化細胞鳥苷三磷酸 (guanosine triphosphate, GTP) 生合成的速率限制步驟，為調節細胞內 GTP 濃度的關鍵蛋白。哺乳動物細胞內 IMPDH 已被證實可於體內、外環境形成細胞蛇，其細胞蛇之可能功能為促進 GTP 合成，進而平衡細胞在不同生理狀態下對 GTP 的需求與生產。IMPDH 細胞蛇已被證實與免疫細胞、癌細胞及多能性幹細胞 (pluripotent stem cell) 的快速增殖特性有關。這些細胞對於糖解作用 (glycolysis) 的共同偏好，意味著細胞蛇與增殖細胞內之代謝狀態具有相關性。然而，過去礙於缺乏適當之細胞及動物模型，無法對 IMPDH 細胞蛇的功能及重要性提出直接證據。因此，本研究旨在透過點突變抑制 IMPDH 聚合化，調查細胞蛇參與於哺乳動物細胞代謝之調控。在小鼠胚胎發育過程以及多能性幹細胞中，IMPDH 細胞蛇的形成與細胞代謝之活化呈正相關。利用 IMPDH2 點突變建立無法形成細胞蛇之胚胎幹細胞 (embryonic stem cell) 模型，發現細胞蛇在維持糖解作用所衍生之核苷酸 (nucleotide) 生合成當中具有極其重要的作用。此外，在多種人類癌細胞組織切片中可觀察到 IMPDH 細胞蛇的表現，特別是與子宮頸癌 (cervical cancer) 的發生具有顯著相關性。透過建立無法形成細胞蛇之 IMPDH2 點突變癌細胞株，證明細胞蛇對於子宮頸癌細胞以及子宮內膜癌 (endometrial cancer) 細胞內糖解作用以及核苷酸生合成的維持至關重要。綜上所述，此研究揭示細胞蛇於快速生長且依賴糖解作用的細胞代謝當中扮演著調節角色。有鑒於 IMPDH 對免疫及腫瘤代謝的重要臨床價值，本研究結果可為 IMPDH 相關之臨床應用提供重要資訊。 | zh_TW |
| dc.description.abstract | The cytoophidium is an evolutionarily conserved subcellular structure formed by metabolic enzymes. In mammals, inosine monophosphate dehydrogenase (IMPDH), which catalyzes the rate-limiting step in guanosine triphosphate (GTP) biosynthesis, is one of the well-studied cytoophidium-forming enzymes. Forming cytoophidium prevents feedback inhibition of IMPDH, facilitating nucleotide production in hyperproliferating cells such as developing thymocytes, pluripotent stem cells, and cancer cells. The shared preference for glycolysis among these cells implies a link between the cytoophidium and the metabolic status of proliferating cells. However, direct evidence for the physiological significance of IMPDH cytoophidium has been lacking due to the lack of appropriate models in the past. Therefore, this study aims to investigate how cytoophidium is involved in the coordination of mammalian cell metabolism by hindering IMPDH filamentation. The formation of IMPDH cytoophidium is positively correlated with the active cell metabolism in mouse embryo development and pluripotent stem cells. By using IMPDH2 point mutation embryonic stem cell models, which are unable to form the cytoophidium, the utmost importance of the cytoophidium in maintaining the glycolysis-derived nucleotide synthesis is revealed. Furthermore, IMPDH cytoophidia are observed in various human cancer tissues, notably in almost half of the cervical carcinoma samples but not in normal cervical tissues. The essential role of the cytoophidium in supporting nucleotide synthesis via glycolysis is demonstrated in cervical and uterine cancer through the establishment of mutant cancer cell lines with IMPDH2 point mutation that impedes polymerization. Collectively, these findings suggest a regulatory role of cytoophidium in the metabolism of rapidly growing and glycolytic-reliant cells. Given that IMPDH is a potential drug target for autoimmune, infectious diseases, and cancer, this insight may shed light on new avenues in cell biology and medicine. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-09-15T17:01:09Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-09-15T17:01:09Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract iv Table of contents v List of abbreviations vii List of figures ix List of tables xii Chapter 1. Introduction 1 Cytoophidium 1 IMPDH 2 Cytoophidium in animal physiology 5 Glycolytic metabolism: a common phenomenon among pluripotent stem cells (PSCs) and cancer cells 7 Metabolism in embryo development 9 Cytoophidium in PSCs 10 Cytoophidium in cancer 11 Perspective 17 Chapter 2. Correlation of cytoophidium formation and glycolytic metabolism in mouse embryos and pluripotent stem cells (PSCs) 19 Introduction 19 Materials and methods 22 Results 27 Discussion 32 Chapter 3. Roles of IMPDH cytoophidium in the metabolism of mouse ESCs 44 Introduction 44 Materials and methods 47 Results 54 Discussion 60 Chapter 4. Significance of IMPDH cytoophidium in cancer cell metabolism 71 Introduction 71 Materials and methods 73 Results 80 Discussion 87 Chapter 5. Discussion 105 Supplementary information 111 References 122 Appendics 133 Appendix A. Raw data of western blot. 133 Appendix B. List of publications derived during PhD study. 142 | - |
| dc.language.iso | en | - |
| dc.title | 探討哺乳動物肌苷酸脫氫酶細胞蛇於細胞代謝之角色 | zh_TW |
| dc.title | Investigating Roles of IMPDH Cytoophidium in Mammalian Cell Metabolism | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 劉冀瓏;白麗美;林劭品;楊尚訓;李士傑 | zh_TW |
| dc.contributor.oralexamcommittee | Ji-Long Liu;Li-Mei Pai;Shau-Ping Lin;Shang-Hsun Yang;Shyh-Jye Lee | en |
| dc.subject.keyword | 細胞蛇,肌苷酸脫氫酶,胚胎幹細胞,癌細胞,糖解作用,核苷酸生合成,細胞代謝, | zh_TW |
| dc.subject.keyword | Cytoophidium,IMPDH,Embryonic stem cells,Cancer cells,Glycolysis,Nucleotide biosynthesis, | en |
| dc.relation.page | 142 | - |
| dc.identifier.doi | 10.6342/NTU202403679 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-08-10 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 生物科技研究所 | - |
| Appears in Collections: | 生物科技研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-112-2.pdf Restricted Access | 35.79 MB | Adobe PDF |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.