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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.author | Hao－Hung Chang | en |
| dc.contributor.author | 張皓閎 | zh_TW |
| dc.date.accessioned | 2021-07-01T08:13:13Z | - |
| dc.date.available | 2021-07-01T08:13:13Z | - |
| dc.date.issued | 2003 | |
| dc.identifier.citation | 1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. 971-983. 2. Gusella, J. F. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306, 234-238 (1983). 3. Young, A. B. Huntington’s disease and other trinucleotide repeat disorders. (2ed. Martin, J. B.) (New York, New York, USA, 1998). 4. Brinkman, R. R., Mezei, M. M., Theilmann, J., Almqvist, E. & Hayden, M. R. The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size. Am. J. Hum. Genet. 60, 1202-1210 (1997). 5. Vonsattel, J.-P. & DiFiglia, M. Huntington disease. J. Neuropathol. Exp. Neurol. 57, 369-384 (1998). 6. DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science277, 1990-1993 (1997). 7. Nance, M. A., V, M.-H., Breningstall, G., Wick, M. J. &McGlennen, R. C. Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington’s disease. Neurology 52, 392-394(1999). 8. Roizin, L., Stellar, S. & Liu, J. C. Neuronal nuclear-cytoplasmic changes in Huntington’s chorea: electron microscope investigations. (Chase, T.N., Wexier, N.S. and Barbeau, A., Raven Press, New York, 1979). 9. Davies, S. W. et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90, 537-548 (1997). 10. Perutz, M. F., Johnson, T., Suzuki, M. & Finch, J. T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc. Natl Acad. Sci. USA 91, 5355-5358 (1994). 11. Stott, K., Blackburn, J. M., Butler, P. J. & Perutz, M. Incorporation of glutamine repeats makes protein oligomerize: implications for neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 92, 6509-65 13 (1995). 12. Fesus, L. & Thomazy, V. Searching for function of tissue transglutaminase: its possible involvement in biochemical pathway of programmed cell death. Advances in Experimental Biology 231,119-134 (1988). 13. Kahlem, P., Green, H. & Dijan, P. Transglutaminase action imitates Huntington’s disease : selective polymerization of Huntingtin containing expanded polyglutamine. Molecular Cell 1, 595-601 (1998). 14. Karpuj, M. V. et al. Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington’s disease brain nuclei. Proc. Natl A cad. Sci. USA 96, 73 88-7393 (1999). 15. Cariello, L. et al. Transglutaminase activity is related to CAG repeat length in patients with Huntington’s disease. Human Genetics 98, 633-635. (1996). 16. McCampbell, A. & Fischbeck, K. H. Polyglutamine and CBP: fatal attraction Nat. Med. 7, 528-530 (2001). 17. Nucifora, F. C., Jr. et al. Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular Toxicity. Science 291, 2423-2428 (2001). 18. Steffan, J. S. et al. The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl .Acad. Sci. USA 97, 6763-6768 (2000). 19. Shimohata, T. et al. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nat. Genet. 26, 29-36 (2000). 20. Waelter, S. et al. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell 12, 1393-1407 (2001). 21. Charles, V. et al. Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington’s disease patients and transgenic mouse models. Neuroscience Letters 289, 29-32 (2000). 22. Jana, N. R., Tanaka, M., Wang, G.-h. & Nukina, N. Polyglutamine length-dependent interaction of Hsp40and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet.9, 2009-2018 (2000). 23. Sieradzan, K. A. et al. Huntington’s disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp. Neurol.156, 92-99 (1999). 24. Becher, M. W. et al. Intranuclear neuronal inclusions in Huntington’s disease and dentatorubral and pallidoluysian atrophy:correlation between the density of inclusions and ITl5 CAG triplet repeat length. Neurobiol. Dis. 4, 387-97 (1998). 25. Ross, C. A. Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases Neuron 19, 1147-1150 (1997). 26. Martindale, D. et al. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat. Genet. 18, 150-154 (1998). 27. Hackam, A. S. et al. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J. Cell Biol. 141,1097-1105 (1998). 28. Klement, I. A. et al. Ataxin-1 nuclear localization and aggregation:role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95, 41-53 (1998). 29. Saudou, F., Finkbeiner, S., Devys, D. & Greenberg, M. E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95,55-66 (1998). 30. Floyd,J. A. & Hamilton, B. A. Intranuclear inclusions and the ubiquitin-proteasome pathway: digestion of a red herring Neuron24, 765-766 (1999). 31. Kim, T. W. & Tanzim, R. E. Neuronal intranuclear inclusions in polyglutamine diseases: nuclear weapons or nuclear fallout Neuron 21, 657-669 (1998). 32. Orr, H. T. Beyond the Qs in the polyglutamine diseases. Genes Devl. 15, 925-932 (2001). 33. Sisodia, S. S. Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial Cell 95, 1-4 (1998). 34. Gerber, H. P. et al. Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science 263,808-811 (1994). 35. Nucifora, F. C. J. et al. Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423-2428 (2001). 36. Steffan, J. S., Kazantsev, A., Spasic-Boskovic, O., Greenwald, M., Zhu, Y.Z., Gohler, H., Wanker, E.E., Bates, G.P., Housman, D.E. and Thompson, L.M. The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl Acad. Sci. USA, 97, 6763-6768 (2000). 37. lana, N. R., Zemskov, E. A., Wang, G. & Nukina, N. Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Hum. Mol. Genet. 10, 1049-1059 (2001). 38. Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292,1552-1555 (2001). 39. Kazemi-Esfarjani, P. & Benzer, S. Genetic suppression of polyglutamine toxicity in Drosophila. Science 287, 1837-1840 (2000). 40. Warrick,J. M. et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 23, 425-428 (1999). 41. Sherman, M. Y. & Goldberg, A. L. Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron 29, 15-32 (2001). 42. Goldberg, Y. P. et al. Cleavage of buntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. . Nature Genetics 13, 442-449 (1996). 43. Wellington, C. L. et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. Journal of Biological Chemistry 273, 9158-9167 (1998). 44. Liu, Y. F. Expression of polyglutamine-expanded huntingtin activates the SEK1-JNK pathway and induces apoptosis in a hippocampal neuronal cell line. Journal of Biological Chemistry 273, 28873-28877 (1998). 45. Nishitoh, H., Matsuzawa, A., Tobiume, K., Saegusa, K., Takeda, K., Inoue, K., Hori, S., Kalcizuka, A., and Ichijo, H. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Devl. 16,1345-1355 (2002). 46. Fahn, S., Marsden, C. D. & Calne, D. B. Classification and investigation of dystonia. In Movement disorder 2, 332-358 (1987). 47. Nygaard, T. G., Marsden, C. D. & Duvoisin, R. C. Dopa-responsive dystonia. Adv. Neurol. 50, 377-384 (1988). 48. Fahn, S. Clinical variants of idiopathic torsion dystonia. J. Neurol. Neurosurg. Psychiatry Supplement (1989). 49. Segawa, M., Hosaka, A., Miyagawa, F., Nomura, Y. & Imai, H. Hereditary progressive dystonia with marked diurnal fluctuation. Adv Neurol. 14, 215-233 (1976). 50. Nagatsu, T., Levitt, M. & Usenfriend, S. Tyrosine hydroxylase:-initail step in norepinephrine biosynthesis. J. Biol. Chem. 239, 2910-2917 (1964). 51. Duch, D. S. & Smith, G. K. Biosynthesis and fuction of tetrahydrobiopterin. .J. Nutr Biochem. 2, 411-423 (1991). 52. Kaufman, S. New tetrahydrobiopeterin-dependent systems. Annu. Rev. Nutr. 13, 802-805 (1993). 53. Hirano, M., Yanagihara, T. & Ueno, S. Donimant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia. Ann. Neurol. 44, 365-37 1 (1998). 54. Hwu., W. L., Chiou, Y. W., Lai, S. Y. & Lee, Y. M. Dopa-responsive dystonia is induced by a dominant-negative mechanism. Annal Neurol. 48, 609 - 613 (2000). 55. Carmichael, J., Vacher, C. & Rubinsztein, D. C. The bacterial chaperonin GroEL requires GroES to reduce aggregation and cell death in a COS-7 cell model of Huntington’s disease. Neuroscience Letters 330, 270-274 (2002). 56. Chuang, J.-Z. et al. Characterization of a Brain-enriched Chaperone, MRJ, That Inhibits Huntingtin Aggregation and Toxicity Independently. J. Biol. Chem. 277, 19831-19838 (2002). 57. Chai, Y., Koppenhafer, S. L., Bonini, N. M. & Paulson, H. L.Analysis of the Role of Heat Shock Protein (Hsp) Molecular Chaperones in Polyglutamine Disease. J. Neurosci. 19, 10338-10347 (1999). 58. Wyttenbach, A. et al. Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum. Mol. Genet. 11, 1137-1151 (2002). 59. Jiang, H., Nucifora, F. C., Jr, Ross, C. A. & DeFranco, D. B. Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding protein. Hum. Mol. Genet. 12, 1-12 (2003). 60. Kobayashi, Y. et al. Chaperones Hsp70 and Hsp40 Suppress Aggregate Formation and Apoptosis in Cultured Neuronal Cells Expressing Truncated Androgen Receptor Protein with Expanded Polyglutamine Tract. J. Biol. Chem. 275, 8772-8778 (2000). 61. Wyttenbach, A. et al. Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington’s disease. Proc. Natl. Acad. Sci. USA 97, 2898-2903 (2000). 62. Stenoien, D. et al. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-l, and are suppressed by the HDJ-2 chaperone. Hum. Mol. Genet. 8, 73 1-741 (1999). 63. Cyr DM, Langer T & MG, D. Dna-J like proteins: molecular chaperones and specific regulators of Hsp 70. Trends Biochem. Sci. 19, 176-181 (1994) | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75441 | - |
| dc.description.abstract | 我們研究室在 GCH ( GTP cyclohydrogenase I）的 Hela dominant negative 細胞模型中分離出來的一個新的基因（ BC1）。 BC1在不具有 dominant negative 機制的細胞中表現較多，而且能幫助 GCH 聚合體蛋白組合成穩定的結構。故 BC1可能參與了細胞內蛋白質的折疊和分解的機制。近來一些研究報導指出許多蛋白質像是 amy1oid, tau ，-synuclein and polyglutamine containing proteins 的聚集和不正常的折疊都與遺傳性神經退化疾病有關。因此我們探討 BC1對於其中的一種神經退化疾病一漢丁頓氏舞蹈症的影響。
神經細胞死亡和細胞內有蛋白質聚集，是漢丁頓氏舞蹈症的特徵。突變 Huntingtin 蛋白質的 N 端片段就是造成蛋白質聚集和神經細胞死亡的元兇。在我們的研究中，我們發現 BC1能避免 polyQ－Huntingtin 所引起的蛋白質聚集和神經細胞死亡，此外 BC1 與 Huntingtin 更有些微的交互作用，而BC1在細胞內的分子作用機制則需要再進一步的研究。 | zh_TW |
| dc.description.abstract | A novel gene, BC1, was isolated from the GCH (GTP cyclohydrogenase I) Dominant negative cell models. BC1 expressed mainly in the non-DN cells, and had effect on stabilizing polymeric GCH proteins. It seems that BC1 may be involved in folding and degradation pathway. There are many neurodegenerative diseases involved aggregation and deposition of misfolded proteins such as amyloid β, tau , α-synuclein and polyglutamine containing proteins been reported. We investigate that if BC1 may have effect on misfolded protein induced neurodegenerative disease. Neuronal loss and intraneuronal protein aggregates are characteristics of Huntington’s disease (HD), caused by an expanded polyglutamine [polyQ] tract in the disease protein. N-terminal fragments of mutant huntingtin produce intracellular aggregates and cause toxicity. In this study, we found that BC1 can inhibit polyQ-Htt induced aggregation, have moderate interaction with Htt, and may suppress polyQ-Htt induced cell toxicity. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-01T08:13:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2003 | en |
| dc.description.tableofcontents | Chinese Abstract 1 English Abstract 2 Abbreviation 3 1. Introduction 1.1 Huntington’s disease 4 1.2 Protein aggregation in HD 5 1.3 Pathogenesis mechanism of HD 7 1.4 HPD/DRDandGCH 10 1.5 A novel gene BCl 11 2. Material and Method 2.1 Plasmid 13 2.2 Cell Culture and transfection 13 2.3 Westernblot 14 2.4 immunocytochemestry 14 2.5 Co-immunoprecipitation experiments 15 2.6 Quantification of polyQ-Htt aggregation 15 2.7 Flow cytometry analysis 16 3. Result 3.1 Htt exon 1 aggregates in HEK293 stable cell line and induces cell toxicity 18 3.2 BC1 prevents aggregated Huntingtin formation 19 3.3 Interaction with BC1 and huntingtin 20 3.4 BC1 can reduce polyglutamine induced cell toxicity 21 4. Discussion 4.1 PolyQ-Htt aggregation in HEK293 stable cell lines 22 4.2 Hsp70 and BC1 can prevent aggregation formation 22 4.3 The interaction of BC1 and polyQ-Htt 23 4.4 Conclusion: the function of the novel gene BC1 24 5. Rcfrrence 25 6. Figures and tables 34 7. Appendix 47 | |
| dc.language.iso | zh-TW | |
| dc.title | 新奇基因 BC1在 Huntingtin 所引起的蛋白質聚集及細胞毒性上的研究 | zh_TW |
| dc.title | A novel gene BC1 on huntingtin induced aggregation and ce11 toxicity | en |
| dc.date.schoolyear | 91-2 | |
| dc.description.degree | 碩士 | |
| dc.relation.page | 58 | |
| dc.rights.note | 未授權 | |
| dc.contributor.author-dept | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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