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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳美如 | |
dc.contributor.author | Ching-Yueh Hsieh | en |
dc.contributor.author | 謝青悅 | zh_TW |
dc.date.accessioned | 2021-06-13T01:37:03Z | - |
dc.date.available | 2010-08-08 | |
dc.date.copyright | 2007-08-08 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-15 | |
dc.identifier.citation | Asai, R., Kato, A., Kato, K., Kanamori-Koyama, M., Sugimoto, K., Sairenji, T., Nishiyama, Y. & Kawaguchi, Y. (2006). Epstein-Barr virus protein kinase BGLF4 is a virion tegument protein that dissociates from virions in a phosphorylation-dependent process and phosphorylates the viral immediate-early protein BZLF1. J Virol 80, 5125-34.
Baer, R., Bankier, A. T., Biggin, M. D., Deininger, P. L., Farrell, P. J., Gibson, T. J., Hatfull, G., Hudson, G. S., Satchwell, S. C., Seguin, C. & et al. (1984). DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310, 207-11. Bailly, E., Doree, M., Nurse, P. & Bornens, M. (1989). p34cdc2 is located in both nucleus and cytoplasm; part is centrosomally associated at G2/M and enters vesicles at anaphase. Embo J 8, 3985-95. Blangy, A., Lane, H. A., d'Herin, P., Harper, M., Kress, M. & Nigg, E. A. (1995). Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83, 1159-69. Borza, C. M. & Hutt-Fletcher, L. M. (2002). Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat Med 8, 594-9. Brooks, L., Yao, Q. Y., Rickinson, A. B. & Young, L. S. (1992). Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol 66, 2689-97. Burkitt, D. (1958). A sarcoma involving the jaws in African children. Br J Surg 46, 218-23. Castro, A., Vigneron, S., Bernis, C., Labbe, J. C. & Lorca, T. (2003). Xkid is degraded in a D-box, KEN-box, and A-box-independent pathway. Mol Cell Biol 23, 4126-38. Charles, J. F., Jaspersen, S. L., Tinker-Kulberg, R. L., Hwang, L., Szidon, A. & Morgan, D. O. (1998). The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Curr Biol 8, 497-507. Chen, C. & Okayama, H. (1987). High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7, 2745-52. Chen, M. R., Chang, S. J., Huang, H. & Chen, J. Y. (2000). A protein kinase activity associated with Epstein-Barr virus BGLF4 phosphorylates the viral early antigen EA-D in vitro. J Virol 74, 3093-104. Chien, Y. C., Chen, J. Y., Liu, M. Y., Yang, H. I., Hsu, M. M., Chen, C. J. & Yang, C. S. (2001). Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med 345, 1877-82. Chung, E. & Chen, R. H. (2003). Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint. Nat Cell Biol 5, 748-53. Dalpke, A. H., Thomssen, R. & Ritter, K. (2003). Oxidative injury to endothelial cells due to Epstein-Barr virus-induced autoantibodies against manganese superoxide dismutase. J Med Virol 71, 408-16. D'Angiolella, V., Mari, C., Nocera, D., Rametti, L. & Grieco, D. (2003). The spindle checkpoint requires cyclin-dependent kinase activity. Genes Dev 17, 2520-5. Epstein, M. A., Achong, B. G. & Barr, Y. M. (1964). Virus Particles in Cultured Lymphoblasts from Burkitt's Lymphoma. Lancet 1, 702-3. Feng, W. H., Hong, G., Delecluse, H. J. & Kenney, S. C. (2004). Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol 78, 1893-902. Geley, S., Kramer, E., Gieffers, C., Gannon, J., Peters, J. M. & Hunt, T. (2001). Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J Cell Biol 153, 137-48. Gershburg, E. & Pagano, J. S. (2002). Phosphorylation of the Epstein-Barr virus (EBV) DNA polymerase processivity factor EA-D by the EBV-encoded protein kinase and effects of the L-riboside benzimidazole 1263W94. J Virol 76, 998-1003. Gershburg, E., Raffa, S., Torrisi, M. R. & Pagano, J. S. (2007). Epstein-Barr virus-encoded protein kinase (BGLF4) is involved in production of infectious virus. J Virol 81, 5407-12. Glotzer, M., Murray, A. W. & Kirschner, M. W. (1991). Cyclin is degraded by the ubiquitin pathway. Nature 349, 132-8. Hansen, D. V., Loktev, A. V., Ban, K. H. & Jackson, P. K. (2004). Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Mol Biol Cell 15, 5623-34. Hayes, M. J., Kimata, Y., Wattam, S. L., Lindon, C., Mao, G., Yamano, H. & Fry, A. M. (2006). Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Nat Cell Biol 8, 607-14. Henle, G., Henle, W. & Diehl, V. (1968). Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A 59, 94-101. Henle, W. (1968). Evidence for viruses in acute leukemia and Burkitt's tumor. Cancer 21, 580-6. Ishimi, Y., Komamura-Kohno, Y., You, Z., Omori, A. & Kitagawa, M. (2000). Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2. J Biol Chem 275, 16235-41. Jones, J. F., Shurin, S., Abramowsky, C., Tubbs, R. R., Sciotto, C. G., Wahl, R., Sands, J., Gottman, D., Katz, B. Z. & Sklar, J. (1988). T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med 318, 733-41. Kato, A., Yamamoto, M., Ohno, T., Tanaka, M., Sata, T., Nishiyama, Y. & Kawaguchi, Y. (2006). Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. J Virol 80, 1476-86. Kato, K., Yokoyama, A., Tohya, Y., Akashi, H., Nishiyama, Y. & Kawaguchi, Y. (2003). Identification of protein kinases responsible for phosphorylation of Epstein-Barr virus nuclear antigen leader protein at serine-35, which regulates its coactivator function. J Gen Virol 84, 3381-92. Kawaguchi, Y., Kato, K., Tanaka, M., Kanamori, M., Nishiyama, Y. & Yamanashi, Y. (2003). Conserved protein kinases encoded by herpesviruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1delta. J Virol 77, 2359-68. Ke, P. Y. & Chang, Z. F. (2004). Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway. Mol Cell Biol 24, 514-26. Kieff E., a. R. A. B. (2001). Epstein-Barr virus and its replication. In Fields Virology, pp. 2511?575. Edited by a. P. M. H. e. D. M. Knipe. Philadelphia: Lippincott Williams & Wilkins. Kikuta, H., Taguchi, Y., Tomizawa, K., Kojima, K., Kawamura, N., Ishizaka, A., Sakiyama, Y., Matsumoto, S., Imai, S., Kinoshita, T. & et al. (1988). Epstein-Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease. Nature 333, 455-7. Kotani, S., Tanaka, H., Yasuda, H. & Todokoro, K. (1999). Regulation of APC activity by phosphorylation and regulatory factors. J Cell Biol 146, 791-800. Kraft, C., Herzog, F., Gieffers, C., Mechtler, K., Hagting, A., Pines, J. & Peters, J. M. (2003). Mitotic regulation of the human anaphase-promoting complex by phosphorylation. Embo J 22, 6598-609. Kramer, E. R., Gieffers, C., Holzl, G., Hengstschlager, M. & Peters, J. M. (1998). Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. Curr Biol 8, 1207-10. Kramer, E. R., Scheuringer, N., Podtelejnikov, A. V., Mann, M. & Peters, J. M. (2000). Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol Biol Cell 11, 1555-69. Krosky, P. M., Baek, M. C., Jahng, W. J., Barrera, I., Harvey, R. J., Biron, K. K., Coen, D. M. & Sethna, P. B. (2003). The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. J Virol 77, 7720-7. Kudoh, A., Daikoku, T., Ishimi, Y., Kawaguchi, Y., Shirata, N., Iwahori, S., Isomura, H. & Tsurumi, T. (2006). Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-MCM6-MCM7 complex during Epstein-Barr virus productive replication. J Virol 80, 10064-72. Kudoh, A., Fujita, M., Kiyono, T., Kuzushima, K., Sugaya, Y., Izuta, S., Nishiyama, Y. & Tsurumi, T. (2003). Reactivation of lytic replication from B cells latently infected with Epstein-Barr virus occurs with high S-phase cyclin-dependent kinase activity while inhibiting cellular DNA replication. J Virol 77, 851-61. Lamb, J. R., Michaud, W. A., Sikorski, R. S. & Hieter, P. A. (1994). Cdc16p, Cdc23p and Cdc27p form a complex essential for mitosis. Embo J 13, 4321-8. Le Bot, N., Tsai, M. C., Andrews, R. K. & Ahringer, J. (2003). TAC-1, a regulator of microtubule length in the C. elegans embryo. Curr Biol 13, 1499-505. Lee, C. P., Chen, J. Y., Wang, J. T., Kimura, K., Takemoto, A., Lu, C. C. & Chen, M. R. (2007). Epstein-Barr virus BGLF4 kinase induces premature chromosome condensation through activation of condensin and topoisomerase II. J Virol 81, 5166-80. Lee, M. G. & Nurse, P. (1987). Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327, 31-5. Littlepage, L. E. & Ruderman, J. V. (2002). Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit. Genes Dev 16, 2274-85. Liu, B., Hong, S., Tang, Z., Yu, H. & Giam, C. Z. (2005). HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule. Proc Natl Acad Sci U S A 102, 63-8. Liu, B., Liang, M. H., Kuo, Y. L., Liao, W., Boros, I., Kleinberger, T., Blancato, J. & Giam, C. Z. (2003). Human T-lymphotropic virus type 1 oncoprotein tax promotes unscheduled degradation of Pds1p/securin and Clb2p/cyclin B1 and causes chromosomal instability. Mol Cell Biol 23, 5269-81. Liu, L., Amy, V., Liu, G. & McKeehan, W. L. (2002). Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells. In Vitro Cell Dev Biol Anim 38, 582-94. Liu, L. & McKeehan, W. L. (2002). Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity. Genomics 79, 124-36. Maeda, I., Kohara, Y., Yamamoto, M. & Sugimoto, A. (2001). Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol 11, 171-6. Markus, S. M., Taneja, S. S., Logan, S. K., Li, W., Ha, S., Hittelman, A. B., Rogatsky, I. & Garabedian, M. J. (2002). Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus. Mol Biol Cell 13, 670-82. Moshe, Y., Boulaire, J., Pagano, M. & Hershko, A. (2004). Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. Proc Natl Acad Sci U S A 101, 7937-42. Moss, T. N., Vo, A., McKeehan, W. L. & Liu, L. (2007). UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation. In Vitro Cell Dev Biol Anim 43, 139-46. Nasmyth, K. (2001). Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annu Rev Genet 35, 673-745. Nasmyth, K. (2005). How do so few control so many? Cell 120, 739-46. Niedobitek, G., Young, L. S., Lau, R., Brooks, L., Greenspan, D., Greenspan, J. S. & Rickinson, A. B. (1991). Epstein-Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase. J Gen Virol 72 ( Pt 12), 3035-46. Nigg, E. A. (2001). Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2, 21-32. Nurse, P. & Thuriaux, P. (1980). Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics 96, 627-37. Old, L. J., Boyse, E. A., Oettgen, H. F., Harven, E. D., Geering, G., Williamson, B. & Clifford, P. (1966). Precipitating Antibody in Human Serum to an Antigen Present in Cultured Burkitt's Lymphoma Cells. Proc Natl Acad Sci U S A 56, 1699-1704. Pan, J. & Chen, R. H. (2004). Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae. Genes Dev 18, 1439-51. Peters, J. M. (2006). The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7, 644-56. Peters, J. M., King, R. W., Hoog, C. & Kirschner, M. W. (1996). Identification of BIME as a subunit of the anaphase-promoting complex. Science 274, 1199-201. Pfleger, C. M. & Kirschner, M. W. (2000). The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev 14, 655-65. Reed, S. I., Ferguson, J. & Groppe, J. C. (1982). Preliminary characterization of the transcriptional and translational products of the Saccharomyces cerevisiae cell division cycle gene CDC28. Mol Cell Biol 2, 412-25. Reimann, J. D., Freed, E., Hsu, J. Y., Kramer, E. R., Peters, J. M. & Jackson, P. K. (2001). Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105, 645-55. Reis, A., Levasseur, M., Chang, H. Y., Elliott, D. J. & Jones, K. T. (2006). The CRY box: a second APCcdh1-dependent degron in mammalian cdc20. EMBO Rep 7, 1040-5. Schroer, A., Schneider, S., Ropers, H. & Nothwang, H. (1999). Cloning and characterization of UXT, a novel gene in human Xp11, which is widely and abundantly expressed in tumor tissue. Genomics 56, 340-3. Schwab, M., Neutzner, M., Mocker, D. & Seufert, W. (2001). Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. Embo J 20, 5165-75. Sculley, T. B., Walker, P. J., Moss, D. J. & Pope, J. H. (1984). Identification of multiple Epstein-Barr virus-induced nuclear antigens with sera from patients with rheumatoid arthritis. J Virol 52, 88-93. Shibata, D., Tokunaga, M., Uemura, Y., Sato, E., Tanaka, S. & Weiss, L. M. (1991). Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like carcinoma. Am J Pathol 139, 469-74. Sikorski, R. S., Boguski, M. S., Goebl, M. & Hieter, P. (1990). A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60, 307-17. Sixbey, J. W., Vesterinen, E. H., Nedrud, J. G., Raab-Traub, N., Walton, L. A. & Pagano, J. S. (1983). Replication of Epstein-Barr virus in human epithelial cells infected in vitro. Nature 306, 480-3. Smith, R. F. & Smith, T. F. (1989). Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus. J Virol 63, 450-5. Stemmann, O., Zou, H., Gerber, S. A., Gygi, S. P. & Kirschner, M. W. (2001). Dual inhibition of sister chromatid separation at metaphase. Cell 107, 715-26. Swedlow, J. R. & Hirano, T. (2003). The making of the mitotic chromosome: modern insights into classical questions. Mol Cell 11, 557-69. Tang, Z., Li, B., Bharadwaj, R., Zhu, H., Ozkan, E., Hakala, K., Deisenhofer, J. & Yu, H. (2001). APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell 12, 3839-51. Tang, Z., Shu, H., Oncel, D., Chen, S. & Yu, H. (2004). Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell 16, 387-97. Thompson, M. P. & Kurzrock, R. (2004). Epstein-Barr virus and cancer. Clin Cancer Res 10, 803-21. Thornton, B. R., Ng, T. M., Matyskiela, M. E., Carroll, C. W., Morgan, D. O. & Toczyski, D. P. (2006). An architectural map of the anaphase-promoting complex. Genes Dev 20, 449-60. Vodermaier, H. C., Gieffers, C., Maurer-Stroh, S., Eisenhaber, F. & Peters, J. M. (2003). TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Curr Biol 13, 1459-68. Wan, Y., Liu, X. & Kirschner, M. W. (2001). The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction. Mol Cell 8, 1027-39. Wang, J. T., Yang, P. W., Lee, C. P., Han, C. H., Tsai, C. H. & Chen, M. R. (2005). Detection of Epstein-Barr virus BGLF4 protein kinase in virus replication compartments and virus particles. J Gen Virol 86, 3215-25. Weinstein, J. (1997). Cell cycle-regulated expression, phosphorylation, and degradation of p55Cdc. A mammalian homolog of CDC20/Fizzy/slp1. J Biol Chem 272, 28501-11. Wu, T. C., Mann, R. B., Epstein, J. I., MacMahon, E., Lee, W. A., Charache, P., Hayward, S. D., Kurman, R. J., Hayward, G. S. & Ambinder, R. F. (1991). Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. Am J Pathol 138, 1461-9. Yeh, S. W. (2006). Epstein-Barr virus BGLF4 protein kinase regulates cellular ART27 protein stability through an Anaphase-promoting complex/Cyclosome (APC/C) dependent pathway. Master Thesis of Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan. Yudkovsky, Y., Shteinberg, M., Listovsky, T., Brandeis, M. & Hershko, A. (2000). Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint. Biochem Biophys Res Commun 271, 299-304. Yue, W., Gershburg, E. & Pagano, J. S. (2005). Hyperphosphorylation of EBNA2 by Epstein-Barr virus protein kinase suppresses transactivation of the LMP1 promoter. J Virol 79, 5880-5. Zeng, Y. (1985). Seroepidemiological studies on nasopharyngeal carcinoma in China. Adv Cancer Res 44, 121-38. Zhao, H., Wang, Q., Zhang, H., Liu, Q., Du, X., Richter, M. & Greene, M. I. (2005). UXT is a novel centrosomal protein essential for cell viability. Mol Biol Cell 16, 5857-65. zur Hausen, H., Schulte-Holthausen, H., Klein, G., Henle, W., Henle, G., Clifford, P. & Santesson, L. (1970). EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature 228, 1056-8. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30111 | - |
dc.description.abstract | EB 病毒 (Epstein-Barr virus, EBV) 是一種與許多人類惡性腫瘤的發生有高度關聯性的疱疹病毒。在我們實驗室先前的研究中發現,若表現 EB 病毒中唯一的serine/threonine 蛋白質激酶 BGLF4 會造成細胞在尚未進入有絲分裂時期就產生染色體濃縮,核膜溶解及細胞骨架重組等類似有絲分裂時期的現象,顯示 BGLF4 可能以類似細胞蛋白質激酶 Cdk1 的作用影響細胞週期所發生的事件。Cdk1 的主要作用之一是調控 anaphase promoting complex/cyclosome (APC/C) 活性,APC/C 是一個調控細胞週期重要的 E3 ubiquitin ligase,APC/CCdc20 可造成 cyclin A、cyclin B及securin 等蛋白質的降解,促進細胞從 metaphase 進入 anaphase。先前的研究中發現 BGLF4 會透過 APC/CCdc20 促進一個位於中心體的 ART-27蛋白質的降解,暗示 BGLF4 可能會影響 APC/CCdc20 的E3 ubiquitin ligase活性。共同免疫沉澱實驗的結果證明在in vivo情況下BGLF4可以與 APC/C 的活化單位 Cdc20 產生交互作用,而in vitro IP-kinase assay則進一步證明在 in vitro 情況下 BGLF4 可以磷酸化 Cdc20。利用短暫轉染的實驗觀察到共同表現 BGLF4 會造成 Cdc20表現量增加,並證明BGLF4是藉由增加Cdc20蛋白質的穩定性來影響Cdc20 的表現量。文獻指出 BGLF4 的細胞同源蛋白 Cdk1 可以藉由磷酸化 APC/C 的次單位促進 APC/CCdc20 活性,但是表現BGLF4 的細胞並沒有發現主要次單位 Cdc27 有明顯磷酸化的情況。此外,BGLF4 不會造成 APC/CCdc20 已知的受質 cyclin B1 的降解。更進一步探討 BGLF4 對 ART-27 可能的調控機制,在免疫螢光染色實驗中觀察發現 BGLF4 會造成 ART-27 表現的位置改變,並且在 in vitro 情況下 BGLF4 可以磷酸化 ART-27。最後本篇研究提出 BGLF4 調控 APC/CCdc20 的可能作用模式,即 BGLF4 可以透過磷酸化 Cdc20 增加 Cdc20 蛋白質的穩定性,藉由提高Cdc20 的表現量增加 APC/CCdc20 的活性,但是此時 APC/CCdc20 活性仍不足以造成所有受質的降解,BGLF4 可以透過磷酸化 ART-27 並幫助其與 APC/CCdc20 交互作用,而促進 ART-27 蛋白質降解。 | zh_TW |
dc.description.abstract | Epstein-Barr virus (EBV) is a gamma-herpesvirus closely associated with human malignant diseases. Our previous study has demonstrated that expression of BGLF4 kinase induces multiple premature mitotic events such as chromosome condensation, nuclear lamina disassembly, and cytoskeleton rearrangement through Cdk1 mimicry. One of the major functions of Cdk1 is to regulate anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase which promotes metaphase to anaphase transition by targeting substrates such as cyclin A, cyclin B, and securin for proteasomal degradation. Previously, co-expression of BGLF4 kinase induced the degradation of a centrosomal protein ART-27 through APC/CCdc20 ubiquitination pathway, suggesting that BGLF4 may regulate the E3 ubiquitin ligase activity of APC/CCdc20. To search for possible mechanisms involved, the physical interaction of Cdc20 and BGLF4 in vivo was demonstrated by co-immunoprecipitation in this study. Furthermore, Cdc20 was phosphorylated by BGLF4 in in vitro IP-kinase assay. In co-transfection assays, Cdc20 protein was stabilized by BGLF4 in a dose dependent manner. Because Cdk1 is known to activate APC/C activity through phosphorylating APC/C subunits, Cdc27 was examined for possible phosphorylation induced by BGLF4, and no obvious molecular weight shift was observed. Additionally, we found that the localization of ART-27 was changed upon BGLF4 coexpression and ART-27 was phosphorylated by BGLF4 in vitro. Taken together, we postulate that BGLF4 might stabilize Cdc20 protein through phosphorylation, which may then result in the activation of APC/CCdc20 activity. However, cyclin B1 degradation was not obvious in the presence of BGLF4, suggesting not all APC/CCdc20 substrates are degraded. Thus BGLF4 may also play a role in recruiting ART-27 to APC/CCdc20 for promoting its degradation. Further investigation will be needed to reveal how ART-27 protein stability contributes to BGLF4 induced premature chromosome condensation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T01:37:03Z (GMT). No. of bitstreams: 1 ntu-96-R94445107-1.pdf: 4539079 bytes, checksum: 5ec91fd47a1ff8f3cddbcf9e4b9b32c8 (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 目錄................1
中文摘要............2 英文摘要............3 導論................4 研究動機與目標.....20 材料與方法.........21 實驗結果...........28 討論...............34 圖表...............37 參考文獻...........51 | |
dc.language.iso | zh-TW | |
dc.title | EB 病毒 BGLF4 蛋白質激酶對 ART-27 穩定性及細胞分裂後期促進複合體活性影響之探討 | zh_TW |
dc.title | Effects of Epstein-Barr virus BGLF4 kinase on cellular ART-27 protein stability and APC/CCdc20 activity | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 蔡錦華,黃麗華,張智芬 | |
dc.subject.keyword | 蛋白質激酶,細胞分裂後期促進複合體,穩定性, | zh_TW |
dc.subject.keyword | EBV,BGLF4,ART-27,APC/C, | en |
dc.relation.page | 58 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-16 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
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ntu-96-1.pdf 目前未授權公開取用 | 4.43 MB | Adobe PDF |
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