請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81189完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張明富(Ming-Fu Chang) | |
| dc.contributor.author | Chiao-Yin Sun | en |
| dc.contributor.author | 孫樵隱 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:35:12Z | - |
| dc.date.available | 2021-08-30 | |
| dc.date.available | 2022-11-24T03:35:12Z | - |
| dc.date.copyright | 2021-08-30 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-03 | |
| dc.identifier.citation | 1. Wang YH, Chang SC, Huang C, Li YP, Lee CH, Chang MF. Novel nuclear export signal-interacting protein, NESI, critical for the assembly of hepatitis delta virus. J Virol. 2005 Jul;79(13):8113-20. 2. Huang C, Jiang JY, Chang SC, Tsay YG, Chen MR, Chang MF. Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen. J Virol. 2013 Feb;87(3):1596-604. 3. Kawaguchi K, Okamoto T, Morita M, Imanaka T. Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1. Sci Rep. 2016 Jul 26;6:30183 4. Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P. Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. Nat Genet. 2009 Feb;41(2):234-9. 5. Miousse IR, Watkins D, Rosenblatt DS. Novel splice site mutations and a large deletion in three patients with the cblF inborn error of vitamin B12 metabolism. Mol Genet Metab. 2011 Apr;102(4):505-7. 6. Godlee C, Kaksonen M. From uncertain beginnings: initiation mechanisms of clathrin-mediated endocytosis. J Cell Biol. 2013 Dec 9;203(5):717-25. 7. Tseng LT, Lin CL, Tzen KY, Chang SC, Chang MF. LMBD1 protein serves as a specific adaptor for insulin receptor internalization. J Biol Chem. 2013 Nov 8;288(45):32424-32432. 8. Tseng LT, Lin CL, Pan KH, Tzen KY, Su MJ, Tsai CT, Li YH, Li PC, Chiang FT, Chang SC, Chang MF. Single allele Lmbrd1 knockout results in cardiac hypertrophy. J Formos Med Assoc. 2018 Jun;117(6):471-479. 9. Buers I, Pennekamp P, Nitschke Y, Lowe C, Skryabin BV, Rutsch F. Lmbrd1 expression is essential for the initiation of gastrulation. J Cell Mol Med. 2016 Aug;20(8):1523-33. 10. Hsu WT. Functional analysis of LMBRD1 in neuronal differentiation. NTU. 2010. 11. Li YP. Biochemical characterization of NESI protein involved in the nuclear export pathway. NTU. 2005. 12. Chiu YL. Functional analysis of the putative actin-binding domain of NESI protein. NTU. 2007. 13. Wang HP. Roles of Lmbrd1 gene in cell mitosis. NTU. 2015. 14. Wade RH, Hyman AA. Microtubule structure and dynamics. Curr Opin Cell Biol. 1997 Feb;9(1):12-7. 15. Vale RD. The molecular motor toolbox for intracellular transport. Cell. 2003 Feb 21;112(4):467-80. 16. Downing KH, Nogales E. Tubulin and microtubule structure. Curr Opin Cell Biol. 1998 Feb;10(1):16-22. 17. Goodson HV, Jonasson EM. Microtubules and Microtubule-Associated Proteins. Cold Spring Harb Perspect Biol. 2018 Jun 1;10(6):a022608. 18. Weisenberg RC. Microtubule formation in vitro in solutions containing low calcium concentrations. Science. 1972 Sep 22;177(4054):1104-5. 19. Weisenberg RC, Deery WJ, Dickinson PJ. Tubulin-nucleotide interactions during the polymerization and depolymerization of microtubules. Biochemistry. 1976 Sep 21;15(19):4248-54. 20. Mitchison T, Kirschner M. Dynamic instability of microtubule growth. Nature. 1984 Nov 15-21;312(5991):237-42. 21. Maccioni RB, Cambiazo V. Role of microtubule-associated proteins in the control of microtubule assembly. Physiol Rev. 1995 Oct;75(4):835-64. 22. Mandelkow E, Mandelkow EM. Microtubules and microtubule-associated proteins. Curr Opin Cell Biol. 1995 Feb;7(1):72-81. 23. Bramblett GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VM. Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron. 1993 Jun;10(6):1089-99. 24. Bosc C, Andrieux A, Job D. STOP proteins. Biochemistry. 2003 Oct 28;42(42):12125-32. 25. Andrieux A, Salin PA, Vernet M, Kujala P, Baratier J, Gory-Fauré S, Bosc C, Pointu H, Proietto D, Schweitzer A, Denarier E, Klumperman J, Job D. The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders. Genes Dev. 2002 Sep 15;16(18):2350-64. 26. Guillaud L, Bosc C, Fourest-Lieuvin A, Denarier E, Pirollet F, Lafanechère L, Job D. STOP proteins are responsible for the high degree of microtubule stabilization observed in neuronal cells. J Cell Biol. 1998 Jul 13;142(1):167-79. 27. Belmont LD, Mitchison TJ. Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. Cell. 1996 Feb 23;84(4):623-31. 28. Curmi PA, Andersen SS, Lachkar S, Gavet O, Karsenti E, Knossow M, Sobel A. The stathmin/tubulin interaction in vitro. J Biol Chem. 1997 Oct 3;272(40):25029-36. 29. Jourdain L, Curmi P, Sobel A, Pantaloni D, Carlier MF. Stathmin: a tubulin-sequestering protein which forms a ternary T2S complex with two tubulin molecules. Biochemistry. 1997 Sep 9;36(36):10817-21. 30. Wallon G, Rappsilber J, Mann M, Serrano L. Model for stathmin/OP18 binding to tubulin. EMBO J. 2000 Jan 17;19(2):213-22. 31. Andersen SS. Balanced regulation of microtubule dynamics during the cell cycle: a contemporary view. Bioessays. 1999 Jan;21(1):53-60. 32. Kapoor TM. Metaphase Spindle Assembly. Biology (Basel). 2017 Feb 3;6(1):8. 33. Nicklas RB, Kubai DF, Hays TS. Spindle microtubules and their mechanical associations after micromanipulation in anaphase. J Cell Biol. 1982 Oct;95(1):91-104. 34. Forth S, Kapoor TM. The mechanics of microtubule networks in cell division. J Cell Biol. 2017 Jun 5;216(6):1525-1531. 35. Jordan A, Hadfield JA, Lawrence NJ, McGown AT. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. 36. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004 Apr;4(4):253-65. 37. Jain K, Verma PJ, Liu J. Isolation and handling of mouse embryonic fibroblasts. Methods Mol Biol. 2014;1194:247-52. 38. Sun CY, Wu MS, Lee CC, Chen SH, Lo KC, Chen YH. A novel SNP in the 5' regulatory region of organic anion transporter 1 is associated with chronic kidney disease. Sci Rep. 2018 May 24;8(1):8085. 39. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44-57. 40. Chen TI, Hsu YK, Chou CY, Chen YH, Hsu ST, Liou YS, Dai YC, Chang MF, Chang SC. Hepatitis C Virus NS3 Protein Plays a Dual Role in WRN-Mediated Repair of Nonhomologous End Joining. J Virol. 2019 Oct 29;93(22):e01273-19. 41. Bonne D, Heuséle C, Simon C, Pantaloni D. 4',6-Diamidino-2-phenylindole, a fluorescent probe for tubulin and microtubules. J Biol Chem. 1985 Mar 10;260(5):2819-25. 42. Peng HC, Wang YH, Wen CC, Wang WH, Cheng CC, Chen YH. Nephrotoxicity assessments of acetaminophen during zebrafish embryogenesis. Comp Biochem Physiol C Toxicol Pharmacol. 2010 May;151(4):480-6 43. Deme JC, Hancock MA, Xia X, Shintre CA, Plesa M, Kim JC, Carpenter EP, Rosenblatt DS, Coulton JW. Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4. Mol Membr Biol. 2014 Nov-Dec;31(7-8):250-61. 44. Findeisen P, Mühlhausen S, Dempewolf S, Hertzog J, Zietlow A, Carlomagno T, Kollmar M. Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family. Genome Biol Evol. 2014 Aug 27;6(9):2274-88. 45. Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci. 1992 Jul;102 ( Pt 3):401-16. 46. Janke C, Montagnac G. Causes and Consequences of Microtubule Acetylation. Curr Biol. 2017 Dec 4;27(23):R1287-R1292. 47. Eshun-Wilson L, Zhang R, Portran D, Nachury MV, Toso DB, Löhr T, Vendruscolo M, Bonomi M, Fraser JS, Nogales E. Effects of alpha-tubulin acetylation on microtubule structure and stability. Proc Natl Acad Sci U S A. 2019 May 21;116(21):10366-10371. 48. Cournia Z, Allen TW, Andricioaei I, Antonny B, Baum D, Brannigan G, Buchete NV, Deckman JT, Delemotte L, Del Val C, Friedman R, Gkeka P, Hege HC, Hénin J, Kasimova MA, Kolocouris A, Klein ML, Khalid S, Lemieux MJ, Lindow N, Roy M, Selent J, Tarek M, Tofoleanu F, Vanni S, Urban S, Wales DJ, Smith JC, Bondar AN. Membrane protein structure, function, and dynamics: a perspective from experiments and theory. J Membr Biol. 2015 Aug;248(4):611-40. 49. Stephens DJ. Functional coupling of microtubules to membranes - implications for membrane structure and dynamics. J Cell Sci. 2012 Jun 15;125(Pt 12):2795-804. 50. Wolff J. Plasma membrane tubulin. Biochim Biophys Acta. 2009 Jul;1788(7):1415-33. 51. Drewes G, Ebneth A, Mandelkow EM. MAPs, MARKs and microtubule dynamics. Trends Biochem Sci. 1998 Aug;23(8):307-11. 52. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002 Sep 20;110(6):673-87. 53. LaFlamme SE, Mathew-Steiner S, Singh N, Colello-Borges D, Nieves B. Integrin and microtubule crosstalk in the regulation of cellular processes. Cell Mol Life Sci. 2018 Nov;75(22):4177-4185. 54. Nogales E. Structural insights into microtubule function. Annu Rev Biochem. 2000;69:277-302. 55. Tu HQ, Qin XH, Liu ZB, Song ZQ, Hu HB, Zhang YC, Chang Y, Wu M, Huang Y, Bai YF, Wang G, Han QY, Li AL, Zhou T, Liu F, Zhang XM, Li HY. Microtubule asters anchored by FSD1 control axoneme assembly and ciliogenesis. Nat Commun. 2018 Dec 11;9(1):5277. 56. Bärenz F, Kschonsak YT, Meyer A, Jafarpour A, Lorenz H, Hoffmann I. Ccdc61 controls centrosomal localization of Cep170 and is required for spindle assembly and symmetry. Mol Biol Cell. 2018 Dec 15;29(26):3105-3118. 57. Sedjaï F, Acquaviva C, Chevrier V, Chauvin JP, Coppin E, Aouane A, Coulier F, Tolun A, Pierres M, Birnbaum D, Rosnet O. Control of ciliogenesis by FOR20, a novel centrosome and pericentriolar satellite protein. J Cell Sci. 2010 Jul 15;123(Pt 14):2391-401. 58. Shen M, Cai Y, Yang Y, Yan X, Liu X, Zhou T. Centrosomal protein FOR20 is essential for S-phase progression by recruiting Plk1 to centrosomes. Cell Res. 2013 Nov;23(11):1284-95. 59. Srivastava S, Panda D. A centrosomal protein FOR20 regulates microtubule assembly dynamics and plays a role in cell migration. Biochem J. 2017 Aug 10;474(16):2841-2859. 60. Xu R, Xu Y, Huo W, Lv Z, Yuan J, Ning S, Wang Q, Hou M, Gao G, Ji J, Chen J, Guo R, Xu D. Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate spindle dynamics and chromosome segregation. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10079-E10088. 61. Xu Z, Liu M, Gao C, Kuang W, Chen X, Liu F, Ge B, Yan X, Zhou T, Xie S. Centrosomal protein FOR20 knockout mice display embryonic lethality and left-right patterning defects. FEBS Lett. 2021 May;595(10):1462-1472. 62. Al-Bassam J, Ozer RS, Safer D, Halpain S, Milligan RA. MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments. J Cell Biol. 2002 Jun 24;157(7):1187-96. 63. Stoothoff WH, Johnson GV. Tau phosphorylation: physiological and pathological consequences. Biochim Biophys Acta. 2005 Jan 3;1739(2-3):280-97. 64. Keating TJ, Borisy GG. Centrosomal and non-centrosomal microtubules. Biol Cell. 1999 May-Jun;91(4-5):321-9. 65. Rusan NM, Fagerstrom CJ, Yvon AM, Wadsworth P. Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin. Mol Biol Cell. 2001 Apr;12(4):971-80. 66. Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci. 1992 Jul;102 ( Pt 3):401-16. 67. Hasanpourghadi M, Karthikeyan C, Pandurangan AK, Looi CY, Trivedi P, Kobayashi K, Tanaka K, Wong WF, Mustafa MR. Targeting of tubulin polymerization and induction of mitotic blockage by Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) in human cervical cancer HeLa cell. J Exp Clin Cancer Res. 2016 Mar 31;35:58. 68. Rutsch F, Gailus S, Suormala T, Fowler B. LMBRD1: the gene for the cblF defect of vitamin B12 metabolism. J Inherit Metab Dis. 2011 Feb;34(1):121-6. 69. Galluzzi L, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018 Mar;25(3):486-541. 70. Aits S, Jäättelä M. Lysosomal cell death at a glance. J Cell Sci. 2013 May 1;126(Pt 9):1905-12. 71. Aits S, Kricker J, Liu B, Ellegaard AM, Hämälistö S, Tvingsholm S, Corcelle-Termeau E, Høgh S, Farkas T, Holm Jonassen A, Gromova I, Mortensen M, Jäättelä M. Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay. Autophagy. 2015;11(8):1408-24. 72. Hämälistö S, Stahl JL, Favaro E, Yang Q, Liu B, Christoffersen L, Loos B, Guasch Boldú C, Joyce JA, Reinheckel T, Barisic M, Jäättelä M. Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation. Nat Commun. 2020 Jan 13;11(1):229. 73. Olson OC, Joyce JA. Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat Rev Cancer. 2015 Dec;15(12):712-29. 74. Baudoin NC, Cimini D. A guide to classifying mitotic stages and mitotic defects in fixed cells. Chromosoma. 2018 Jun;127(2):215-227. 75. Funk LC, Zasadil LM, Weaver BA. Living in CIN: Mitotic Infidelity and Its Consequences for Tumor Promotion and Suppression. Dev Cell. 2016 Dec 19;39(6):638-652. 76. Almacellas E, Pelletier J, Day C, Ambrosio S, Tauler A, Mauvezin C. Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability. Autophagy. 2021 Mar;17(3):796-813. 77. Holdgaard SG, Cianfanelli V, Pupo E, Lambrughi M, Lubas M, Nielsen JC, Eibes S, Maiani E, Harder LM, Wesch N, Foged MM, Maeda K, Nazio F, de la Ballina LR, Dötsch V, Brech A, Frankel LB, Jäättelä M, Locatelli F, Barisic M, Andersen JS, Bekker-Jensen S, Lund AH, Rogov VV, Papaleo E, Lanzetti L, De Zio D, Cecconi F. Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites. Nat Commun. 2019 Sep 13;10(1):4176. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81189 | - |
| dc.description.abstract | 先前研究已證明LMBD1可調節細胞表面胰島素受體的內吞作用並介導鈷胺素 (cobalamin) 從溶酶體向細胞質的輸出，但對其在有絲分裂中的功能知之甚少。細胞週期是細胞生長並且分裂成子細胞的動態過程，細胞骨架中的微管在細胞分裂中扮演了重要的角色。本實驗室以LMBD1的抗體進行免疫沉澱將可能與LMBD1蛋白質交互作用的蛋白質純化出來，再透過質譜儀進行分析。在這項研究中，相互作用組 (interactome) 分析數據顯示 LMBD1 參與細胞骨架調節。免疫沉澱實驗亦證明了 LMBD1 與微管蛋白的關聯。此外，LMBD1蛋白質在細胞分裂期的表現量豐富，並且呈現類紡錘絲結構的分佈，暗示LMBRD1基因可能在細胞分裂具有功能性。免疫螢光染色還顯示 LMBD1 與微管在間期和有絲分裂細胞中有共位的現象。微管組裝的體外實驗發現 LMBD1 在體外特異性地加速微管組裝動力學並拮抗長春鹼 (vinblastine) 的微管破壞作用。此外，LMBRD1 敲低(knockdown) 會損害有絲分裂紡錘體的形成，抑制微管蛋白聚合，並減少與有絲分裂相關的微管蛋白乙醯化。而 LMBD1 蛋白質的異位表達可以逆轉乙醯化減少。這些結果顯示 LMBD1 蛋白質穩定微管中間體。此外，來自 Lmbrd1 雜合基因敲除 (Lmbrd1+/-) 小鼠的胚胎成纖維細胞在微管形成、有絲分裂和細胞生長方面表現出異常。總之，LMBD1 在調節微管組裝方面起著關鍵作用，這對細胞有絲分裂過程至關重要。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:35:12Z (GMT). No. of bitstreams: 1 U0001-0308202110551700.pdf: 5611731 bytes, checksum: 3dfcd3bfcab15671912552348e331346 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 中文摘要 I Abstract II 目次 III 緒論 1 一、 LMBRD1基因之相關研究 1 二、 微管結構與動態 3 三、微管與有絲分裂 5 研究主題 7 實驗方法 8 細胞培養 8 小鼠胚胎成纖維細胞培養 8 質體和DNA轉染 8 相互作用組分析 (interactome)：免疫沉澱、質譜和通路 (pathway) 分析 9 西方墨點法分析 10 GST (Glutathione S-transferase) 融合蛋白質之表現與純化 10 GST pulldown測定 11 微管蛋白聚合試驗 11 免疫螢光染色、共軛焦顯微鏡、活細胞成像和 3D 結構重建分析 12 微管形成、細胞週期和多套體 (polypoid) 細胞的流式細胞術分析 13 斑馬魚胚胎分期、morpholino注射和原位雜交 (in situ hybridization) 13 統計分析 15 實驗結果 16 LMBD1 在細胞骨架調節中的潛在作用 16 LMBD1 蛋白促進體外微管組裝 17 LMBD1 可能通過穩定微管參與有絲分裂紡錘體的形成 18 Lmbrd1 雜合敲除 (Lmbrd1+/-) 影響小鼠胚胎成纖維細胞之細胞分裂 19 lmbrd1 缺損影響斑馬魚早期胚胎發育 20 討論 21 結論 26 圖表 27 參考文獻 45 附錄 54 | |
| dc.language.iso | zh-TW | |
| dc.subject | 有絲分裂 | zh_TW |
| dc.subject | LMBRD1 gene | zh_TW |
| dc.subject | LMBD1 蛋白質 | zh_TW |
| dc.subject | 微管組裝 | zh_TW |
| dc.subject | microtubule formation | en |
| dc.subject | mitosis | en |
| dc.subject | LMBRD1 gene | en |
| dc.subject | LMBD1 protein | en |
| dc.title | LMBD1 蛋白質經由調控微管組裝參與細胞有絲分裂 | zh_TW |
| dc.title | LMBD1 protein participates in cell mitosis by regulating microtubule assembly | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 林水龍(Hsin-Tsai Liu),李芳仁(Chih-Yang Tseng),詹迺立,張智芬 | |
| dc.subject.keyword | LMBRD1 gene,LMBD1 蛋白質,微管組裝,有絲分裂, | zh_TW |
| dc.subject.keyword | LMBRD1 gene,LMBD1 protein,microtubule formation,mitosis, | en |
| dc.relation.page | 57 | |
| dc.identifier.doi | 10.6342/NTU202102028 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-04 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-0308202110551700.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 5.48 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。