請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47052
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄧述諄(Shu-Chun Teng) | |
dc.contributor.author | Chui-Wei Wong | en |
dc.contributor.author | 黃翠薇 | zh_TW |
dc.date.accessioned | 2021-06-15T05:46:12Z | - |
dc.date.available | 2020-08-19 | |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-19 | |
dc.identifier.citation | 1. Ai, W., Zheng, H., Yang, X., Liu, Y., and Wang, T.C. (2007). Tip60 functions as a potential corepressor of KLF4 in regulation of HDC promoter activity. Nucleic Acids Res 35, 6137-6149.
2. Andrews, P., Oosterhuis, J. & Damjanov, I. (1987). Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (IRL, Oxford). 3. Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T., and Yamanaka, S. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321, 699-702. 4. Armstrong, L., Saretzki, G., Peters, H., Wappler, I., Evans, J., Hole, N., von Zglinicki, T., and Lako, M. (2005). Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage. Stem Cells 23, 516-529. 5. Barta, T., Vinarsky, V., Holubcova, Z., Dolezalova, D., Verner, J., Pospisilova, S., Dvorak, P., and Hampl, A. (2010). Human embryonic stem cells are capable of executing G1/S checkpoint activation. Stem Cells 28, 1143-1152. 6. Bhattacharya, R., Senbanerjee, S., Lin, Z., Mir, S., Hamik, A., Wang, P., Mukherjee, P., Mukhopadhyay, D., and Jain, M.K. (2005). Inhibition of vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis by the Kruppel-like factor KLF2. J Biol Chem 280, 28848-28851. 7. Bieker, J.J. (2001). Kruppel-like factors: three fingers in many pies. J Biol Chem 276, 34355-34358. 8. Birsoy, K., Chen, Z., and Friedman, J. (2008). Transcriptional regulation of adipogenesis by KLF4. Cell Metab 7, 339-347. 9. Blackburn, E.H. (2001). Switching and signaling at the telomere. Cell 106, 661-673. 10. Blanchon, L., Nores, R., Gallot, D., Marceau, G., Borel, V., Yang, V.W., Bocco, J.L., Lemery, D., Panzetta-Dutari, G., and Sapin, V. (2006). Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1. Biochem Biophys Res Commun 343, 745-753. 11. Blasco, M.A. (2005). Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 6, 611-622. 12. Blasco, M.A. (2007). Telomere length, stem cells and aging. Nat Chem Biol 3, 640-649. 13. Bradshaw, P.S., Stavropoulos, D.J., and Meyn, M.S. (2005). Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nat Genet 37, 193-197. 14. Bryan, T.M., Englezou, A., Dalla-Pozza, L., Dunham, M.A., and Reddel, R.R. (1997). Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 3, 1271-1274. 15. Bryan, T.M., Englezou, A., Gupta, J., Bacchetti, S., and Reddel, R.R. (1995). Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 14, 4240-4248. 16. Cairney, C.J., and Keith, W.N. (2008). Telomerase redefined: integrated regulation of hTR and hTERT for telomere maintenance and telomerase activity. Biochimie 90, 13-23. 17. Celli, G.B., and de Lange, T. (2005). DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 7, 712-718. 18. Cerone, M.A., Londono-Vallejo, J.A., and Bacchetti, S. (2001). Telomere maintenance by telomerase and by recombination can coexist in human cells. Hum Mol Genet 10, 1945-1952. 19. Chan, K.K., Zhang, J., Chia, N.Y., Chan, Y.S., Sim, H.S., Tan, K.S., Oh, S.K., Ng, H.H., and Choo, A.B. (2009). KLF4 and PBX1 Directly Regulate NANOG Expression in Human Embryonic Stem Cells. Stem Cells. 20. Chen, H.F., Kuo, H.C., Chien, C.L., Shun, C.T., Yao, Y.L., Ip, P.L., Chuang, C.Y., Wang, C.C., Yang, Y.S., and Ho, H.N. (2007). Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell differentiation. Hum Reprod 22, 567-577. 21. Chen, X., Xu, H., Yuan, P., Fang, F., Huss, M., Vega, V.B., Wong, E., Orlov, Y.L., Zhang, W., Jiang, J., et al. (2008). Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106-1117. 22. Chen, Z.Y., Rex, S., and Tseng, C.C. (2004). Kruppel-like factor 4 is transactivated by butyrate in colon cancer cells. J Nutr 134, 792-798. 23. Chen, Z.Y., Shie, J., and Tseng, C. (2000). Up-regulation of gut-enriched kruppel-like factor by interferon-gamma in human colon carcinoma cells. FEBS Lett 477, 67-72. 24. Chen, Z.Y., Shie, J.L., and Tseng, C.C. (2002). Gut-enriched Kruppel-like factor represses ornithine decarboxylase gene expression and functions as checkpoint regulator in colonic cancer cells. J Biol Chem 277, 46831-46839. 25. Chen, Z.Y., Wang, X., Zhou, Y., Offner, G., and Tseng, C.C. (2005). Destabilization of Kruppel-like factor 4 protein in response to serum stimulation involves the ubiquitin-proteasome pathway. Cancer Res 65, 10394-10400. 26. Chiambaretta, F., De Graeve, F., Turet, G., Marceau, G., Gain, P., Dastugue, B., Rigal, D., and Sapin, V. (2004). Cell and tissue specific expression of human Kruppel-like transcription factors in human ocular surface. Mol Vis 10, 901-909. 27. Collado, M., Blasco, M.A., and Serrano, M. (2007). Cellular senescence in cancer and aging. Cell 130, 223-233. 28. Counter, C.M., Avilion, A.A., LeFeuvre, C.E., Stewart, N.G., Greider, C.W., Harley, C.B., and Bacchetti, S. (1992). Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 11, 1921-1929. 29. Cullingford, T.E., Butler, M.J., Marshall, A.K., Tham el, L., Sugden, P.H., and Clerk, A. (2008). Differential regulation of Kruppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines. Biochim Biophys Acta 1783, 1229-1236. 30. de Lange, T. (2005). Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19, 2100-2110. 31. Evans, P.M., and Liu, C. (2008). Roles of Krupel-like factor 4 in normal homeostasis, cancer and stem cells. Acta Biochim Biophys Sin (Shanghai) 40, 554-564. 32. Fehrer, C., and Lepperdinger, G. (2005). Mesenchymal stem cell aging. Exp Gerontol 40, 926-930. 33. Ferron, S., Mira, H., Franco, S., Cano-Jaimez, M., Bellmunt, E., Ramirez, C., Farinas, I., and Blasco, M.A. (2004). Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development 131, 4059-4070. 34. Fisch, S., Gray, S., Heymans, S., Haldar, S.M., Wang, B., Pfister, O., Cui, L., Kumar, A., Lin, Z., Sen-Banerjee, S., et al. (2007). Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 104, 7074-7079. 35. Foster, K.W., Liu, Z., Nail, C.D., Li, X., Fitzgerald, T.J., Bailey, S.K., Frost, A.R., Louro, I.D., Townes, T.M., Paterson, A.J., et al. (2005). Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene 24, 1491-1500. 36. Foster, K.W., Ren, S., Louro, I.D., Lobo-Ruppert, S.M., McKie-Bell, P., Grizzle, W., Hayes, M.R., Broker, T.R., Chow, L.T., and Ruppert, J.M. (1999). Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth Differ 10, 423-434. 37. Fruman, D.A., Ferl, G.Z., An, S.S., Donahue, A.C., Satterthwaite, A.B., and Witte, O.N. (2002). Phosphoinositide 3-kinase and Bruton's tyrosine kinase regulate overlapping sets of genes in B lymphocytes. Proc Natl Acad Sci U S A 99, 359-364. 38. Garrett-Sinha, L.A., Eberspaecher, H., Seldin, M.F., and de Crombrugghe, B. (1996). A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. J Biol Chem 271, 31384-31390. 39. Gloor, H. (1950). Schadigungsmuster eines Lethalfaktors (Kr) von Drosophilia melanogaster. Arch Jul Klaus Stiftung 25, 38-44. 40. Greider, C.W., and Blackburn, E.H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413. 41. Harley, C.B., Futcher, A.B., and Greider, C.W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460. 42. Hayflick, L., and Moorhead, P.S. (1961). The serial cultivation of human diploid cell strains. Exp Cell Res 25, 585-621. 43. Hiyama, E., and Hiyama, K. (2007). Telomere and telomerase in stem cells. Br J Cancer 96, 1020-1024. 44. Huang, C.C., Liu, Z., Li, X., Bailey, S.K., Nail, C.D., Foster, K.W., Frost, A.R., Ruppert, J.M., and Lobo-Ruppert, S.M. (2005). KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia. Cancer Biol Ther 4, 1401-1408. 45. Karlseder, J., Hoke, K., Mirzoeva, O.K., Bakkenist, C., Kastan, M.B., Petrini, J.H., and de Lange, T. (2004). The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol 2, E240. 46. Katz, J.P., Perreault, N., Goldstein, B.G., Lee, C.S., Labosky, P.A., Yang, V.W., and Kaestner, K.H. (2002). The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development 129, 2619-2628. 47. Kim, J., Chu, J., Shen, X., Wang, J., and Orkin, S.H. (2008). An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049-1061. 48. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Coviello, G.M., Wright, W.E., Weinrich, S.L., and Shay, J.W. (1994). Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011-2015. 49. Klaewsongkram, J., Yang, Y., Golech, S., Katz, J., Kaestner, K.H., and Weng, N.P. (2007). Kruppel-like factor 4 regulates B cell number and activation-induced B cell proliferation. J Immunol 179, 4679-4684. 50. Kolquist, K.A., Ellisen, L.W., Counter, C.M., Meyerson, M., Tan, L.K., Weinberg, R.A., Haber, D.A., and Gerald, W.L. (1998). Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nat Genet 19, 182-186. 51. Kyo, S., Takakura, M., Taira, T., Kanaya, T., Itoh, H., Yutsudo, M., Ariga, H., and Inoue, M. (2000). Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res 28, 669-677. 52. Lansdorp, P.M. (1997). Lessons from mice without telomerase. J Cell Biol 139, 309-312. 53. Li, Y., McClintick, J., Zhong, L., Edenberg, H.J., Yoder, M.C., and Chan, R.J. (2005). Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood 105, 635-637. 54. Liu, L., DiGirolamo, C.M., Navarro, P.A., Blasco, M.A., and Keefe, D.L. (2004). Telomerase deficiency impairs differentiation of mesenchymal stem cells. Exp Cell Res 294, 1-8. 55. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., et al. (2007). Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55-70. 56. Mao, L., El-Naggar, A.K., Fan, Y.H., Lee, J.S., Lippman, S.M., Kayser, S., Lotan, R., and Hong, W.K. (1996). Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues. Cancer Res 56, 5600-5604. 57. Marion, R.M., Strati, K., Li, H., Tejera, A., Schoeftner, S., Ortega, S., Serrano, M., and Blasco, M.A. (2009). Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4, 141-154. 58. Markoulaki, S., Hanna, J., Beard, C., Carey, B.W., Cheng, A.W., Lengner, C.J., Dausman, J.A., Fu, D., Gao, Q., Wu, S., et al. (2009). Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27, 169-171. 59. Masutomi, K., Yu, E.Y., Khurts, S., Ben-Porath, I., Currier, J.L., Metz, G.B., Brooks, M.W., Kaneko, S., Murakami, S., DeCaprio, J.A., et al. (2003). Telomerase maintains telomere structure in normal human cells. Cell 114, 241-253. 60. McConnell, B.B., Ghaleb, A.M., Nandan, M.O., and Yang, V.W. (2007). The diverse functions of Kruppel-like factors 4 and 5 in epithelial biology and pathobiology. Bioessays 29, 549-557. 61. McEachern, M.J., Krauskopf, A., and Blackburn, E.H. (2000). Telomeres and their control. Annu Rev Genet 34, 331-358. 62. Meyerson, M., Counter, C.M., Eaton, E.N., Ellisen, L.W., Steiner, P., Caddle, S.D., Ziaugra, L., Beijersbergen, R.L., Davidoff, M.J., Liu, Q., et al. (1997). hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90, 785-795. 63. Mohrin, M., Bourke, E., Alexander, D., Warr, M.R., Barry-Holson, K., Le Beau, M.M., Morrison, C.G., and Passegue, E. (2010). Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis. Cell Stem Cell 7, 174-185. 64. Morrison, S.J., Prowse, K.R., Ho, P., and Weissman, I.L. (1996). Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5, 207-216. 65. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N., and Yamanaka, S. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26, 101-106. 66. Nandan, M.O., and Yang, V.W. (2009). The role of Kruppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells. Histol Histopathol 24, 1343-1355. 67. Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317. 68. Panigada, M., Porcellini, S., Sutti, F., Doneda, L., Pozzoli, O., Consalez, G.G., Guttinger, M., and Grassi, F. (1999). GKLF in thymus epithelium as a developmentally regulated element of thymocyte-stroma cross-talk. Mech Dev 81, 103-113. 69. Perkins, A.C., Sharpe, A.H., and Orkin, S.H. (1995). Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature 375, 318-322. 70. Roediger, W.E. (1980). Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut 21, 793-798. 71. Rose, M.D., Winston, F., Hieter, P. (1990). Methods in Yeast Genetics. (Cold Spring Harbor Laboratory, NY, Cold Spring Harbor.). 72. Rowland, B.D., and Peeper, D.S. (2006). KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer 6, 11-23. 73. Segre, J.A., Bauer, C., and Fuchs, E. (1999). Klf4 is a transcription factor required for establishing the barrier function of the skin. Nat Genet 22, 356-360. 74. Shay, J.W., and Wright, W.E. (2006). Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 5, 577-584. 75. Shie, J.L., Chen, Z.Y., Fu, M., Pestell, R.G., and Tseng, C.C. (2000a). Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif. Nucleic Acids Res 28, 2969-2976. 76. Shie, J.L., Chen, Z.Y., O'Brien, M.J., Pestell, R.G., Lee, M.E., and Tseng, C.C. (2000b). Role of gut-enriched Kruppel-like factor in colonic cell growth and differentiation. Am J Physiol Gastrointest Liver Physiol 279, G806-814. 77. Shields, J.M., Christy, R.J., and Yang, V.W. (1996). Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest. J Biol Chem 271, 20009-20017. 78. Simonsen, J.L., Rosada, C., Serakinci, N., Justesen, J., Stenderup, K., Rattan, S.I., Jensen, T.G., and Kassem, M. (2002). Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 20, 592-596. 79. Stadtfeld, M., Maherali, N., Breault, D.T., and Hochedlinger, K. (2008). Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2, 230-240. 80. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872. 81. Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676. 82. Takakura, M., Kyo, S., Kanaya, T., Hirano, H., Takeda, J., Yutsudo, M., and Inoue, M. (1999). Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res 59, 551-557. 83. Tchirkov, A., Rolhion, C., Kemeny, J.L., Irthum, B., Puget, S., Khalil, T., Chinot, O., Kwiatkowski, F., Perissel, B., Vago, P., et al. (2003). Clinical implications of quantitative real-time RT-PCR analysis of hTERT gene expression in human gliomas. Br J Cancer 88, 516-520. 84. Teng, S.C., Chen, Y.Y., Su, Y.N., Chou, P.C., Chiang, Y.C., Tseng, S.F., and Wu, K.J. (2004). Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced transformation. J Biol Chem 279, 14649-14655. 85. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., and Jones, J.M. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147. 86. Tilman, G., Loriot, A., Van Beneden, A., Arnoult, N., Londono-Vallejo, J.A., De Smet, C., and Decottignies, A. (2009). Subtelomeric DNA hypomethylation is not required for telomeric sister chromatid exchanges in ALT cells. Oncogene 28, 1682-1693. 87. Tsai, H.J., Huang, W.H., Li, T.K., Tsai, Y.L., Wu, K.J., Tseng, S.F., and Teng, S.C. (2006). Involvement of topoisomerase III in telomere-telomere recombination. J Biol Chem 281, 13717-13723. 88. Venteicher, A.S., Abreu, E.B., Meng, Z., McCann, K.E., Terns, R.M., Veenstra, T.D., Terns, M.P., and Artandi, S.E. (2009). A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science 323, 644-648. 89. Vera, E., Canela, A., Fraga, M.F., Esteller, M., and Blasco, M.A. (2008). Epigenetic regulation of telomeres in human cancer. Oncogene 27, 6817-6833. 90. Wani, M.A., Wert, S.E., and Lingrel, J.B. (1999). Lung Kruppel-like factor, a zinc finger transcription factor, is essential for normal lung development. J Biol Chem 274, 21180-21185. 91. Wei, D., Kanai, M., Huang, S., and Xie, K. (2006). Emerging role of KLF4 in human gastrointestinal cancer. Carcinogenesis 27, 23-31. 92. Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., and Dalla-Favera, R. (1999). Direct activation of TERT transcription by c-MYC. Nat Genet 21, 220-224. 93. Yajima, T., Yagihashi, A., Kameshima, H., Kobayashi, D., Furuya, D., Hirata, K., and Watanabe, N. (1998). Quantitative reverse transcription-PCR assay of the RNA component of human telomerase using the TaqMan fluorogenic detection system. Clin Chem 44, 2441-2445. 94. Yang, C., Przyborski, S., Cooke, M.J., Zhang, X., Stewart, R., Anyfantis, G., Atkinson, S.P., Saretzki, G., Armstrong, L., and Lako, M. (2008a). A key role for telomerase reverse transcriptase unit in modulating human embryonic stem cell proliferation, cell cycle dynamics, and in vitro differentiation. Stem Cells 26, 850-863. 95. Yang, M.H., Wu, M.Z., Chiou, S.H., Chen, P.M., Chang, S.Y., Liu, C.J., Teng, S.C., and Wu, K.J. (2008b). Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 10, 295-305. 96. Yet, S.F., McA'Nulty, M.M., Folta, S.C., Yen, H.W., Yoshizumi, M., Hsieh, C.M., Layne, M.D., Chin, M.T., Wang, H., Perrella, M.A., et al. (1998). Human EZF, a Kruppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains. J Biol Chem 273, 1026-1031. 97. Yoon, H.S., Chen, X., and Yang, V.W. (2003). Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage. J Biol Chem 278, 2101-2105. 98. Yoon, H.S., Ghaleb, A.M., Nandan, M.O., Hisamuddin, I.M., Dalton, W.B., and Yang, V.W. (2005). Kruppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage. Oncogene 24, 4017-4025. 99. Yoon, H.S., and Yang, V.W. (2004). Requirement of Kruppel-like factor 4 in preventing entry into mitosis following DNA damage. J Biol Chem 279, 5035-5041. 100. Zhang, W., Geiman, D.E., Shields, J.M., Dang, D.T., Mahatan, C.S., Kaestner, K.H., Biggs, J.R., Kraft, A.S., and Yang, V.W. (2000). The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter. J Biol Chem 275, 18391-18398. 101. Zhao, M., Yang, H., Jiang, X., Zhou, W., Zhu, B., Zeng, Y., Yao, K., and Ren, C. (2008). Lipofectamine RNAiMAX: an efficient siRNA transfection reagent in human embryonic stem cells. Mol Biotechnol 40, 19-26. 102. Zhu, X.D., Kuster, B., Mann, M., Petrini, J.H., and de Lange, T. (2000). Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet 25, 347-352. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47052 | - |
dc.description.abstract | 端粒為真核細胞中維持基因體穩定之必須結構,端粒功能的改變與其相關之染色體變異會影響人類老化與癌症的發生。端粒主要是由端粒酵素所合成,而其延長會經由端粒酵素的表現及聚集所調控。端粒酵素的表現會被細胞中轉錄因子所調控。在人類纖維母細胞中缺乏或只有少量之端粒酵素,反之胚胎幹細胞及誘導多功能幹細胞中的端粒酵素活性高。本研究之目標為釐清端粒酵素在胚胎幹細胞中活化之機制。在我們實驗室之前的研究中利用了酵母單雜交(yeast one hybrid)技術發現轉錄因子KLF4可以結合端粒酵素的基因啟動子區。KLF是屬鋅指結構轉錄因子,其在生物學上如增生、分化、成長及凋亡過程都扮演著重要的角色。但是KLF4在癌症及幹細胞中真正扮演的功能尚未被釐清。在本研究中發現KLF4與端粒酵素的關係,而且我們提供線索證明KLF4可能在胚胎幹細胞扮演著角色。KLF4可以在缺乏端粒酵素之ALT細胞及纖維母細胞中有效的活化端粒酵素。反之當我們在端粒酵素表現量多的細胞中抑制KLF4的表現量可以觀察到端粒酵素訊息核糖核酸及活性的下降。此外,我們發現轉錄因子KLF4會結合於端粒酵素之基因啟動子區及調控其表現。在基因剔除KLF4幹細胞中表現端粒酵素可以代替KLF4維持其自我更新功能。在研究中發現在癌細胞及幹細胞中的端粒酵素可能是KLF4其中一個重要調控目標。維持端粒的結構對於幹細胞維持其自我更新功能及癌症形成可能是一個重要的步驟;因此本研究對胚胎幹細胞端粒酵素活化機制進行更一步的研究,希望可以對於胚胎幹細胞中染色體端粒複製機制更加了解。 | zh_TW |
dc.description.abstract | The zinc finger Kruppel-like transcription factor 4 (KLF4) has been implicated in cancer formation and stem cell regulation. However, the function of KLF4 in tumorigenesis and stem cell regulation are poorly understood due to limited knowledge of its targets in these cells. In this study, we have revealed a surprising link between KLF4 and regulation of telomerase, which offers important insight into how KLF4 contributes to cancer formation and stem cell regulation. KLF4 sufficiently activated expression of the human telomerase catalytic subunit, hTERT, in telomerase-low ALT and fibroblast cells, while down-regulation of KLF4 reduced its expression in cancerous and stem cells which normally exhibits high expression. Furthermore, KLF4-dependent induction of hTERT was mediated by a KLF4 binding site in the proximal promoter region of hTERT. In human embryonic stem cells, expression of hTERT replaced KLF4 function to maintain their self-renewal. Therefore, our findings demonstrate that hTERT is one of the major targets of KLF4 in cancer and stem cells to maintain long-term proliferation potential. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:46:12Z (GMT). No. of bitstreams: 1 ntu-99-D95445002-1.pdf: 3670293 bytes, checksum: b30051e8b97ab20563144bbb3b663306 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | TABLE OF CONTENTS
中文摘要 I Abstract II 1. Introduction 1 1.1. Telomere 1 1.2. Telomerase 2 1.3. Kruppel-like transcription factor 4 (KLF4) 5 1.4. Telomere and telomerase in stem cells 8 2. Materials and Methods 11 2.1. Yeast one-hybrid assay 11 2.2. Cell culture 11 2.3. RNA purification 12 2.4. cDNA synthesis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) 14 2.5. Plasmids and transfection 15 2.6. siRNA 16 2.7. Western Blot Analysis 16 2.8. Telomerase activity (TRAP) assay 17 2.9. Luciferase reporter assay 18 2.10. Expression and purification of bacterially expressed GST fusion protein 19 2.11. Electrophoretic mobility shift assay (EMSA) 20 2.12. Chromatin Immunoprecipitation Assay 21 2.13. Immunocytochemistry 22 3. Results 23 3.1. Identification of KLF4 as a regulator of hTERT expression by the yeast one-hybrid screen 23 3.2. Activation of hTERT by KLF4 in fibroblasts and ALT cells having low hTERT expression 24 3.3. Requirement of endogenous KLF4 for maintaining hTERT expression in cancer cells 25 3.4. Direct activation of hTERT by KLF4 through binding to the proximal promoter region 26 3.5. Requirement of KLF4 for maintaining hTERT expression in hESCs 27 4. Discussion 29 5. Conclusion 35 6. Tables 36 Table 1. Primers and oligonucleotides used in this study 36 7. Figures 37 Figure 1. KLF4 binds to the hTERT promoter in the yeast one-hybrid assay. 37 Figure 2. KLF4 binds to the hTERT promoter in the yeast one-hybrid assay (continued). 38 Figure 3. KLF4 induces hTERT transcriptional expression. 39 Figure 4. KLF4 induces telomerase activity. 40 Figure 5. KLF4 induces telomerase activity in BJ1 cells. 41 Figure 6. The specificity of KLF4 induces hTERT transcriptional expression. 42 Figure 7. hTERT expression after knockdown KLF4. 43 Figure 8. siRNA-mediated repression of endogenous KLF4 reduces the expression of hTERT in FaDu and OECM1 cells. 44 Figure 9. siRNA-mediated repression of endogenous KLF4 in FaDu and OECM1 cells. 45 Figure 10. siRNA-mediated repression of endogenous KLF4 reduces the telomerase activity in FaDu and OECM1 cells. 46 Figure 11. KLF4 directly promotes hTERT expression. 47 Figure 12. Identification of a KLF4 binding site proximal to the hTERT core promoter. 48 Figure 13. Recombinant KLF4 binds to hTERT promoter in vitro. 49 Figure 14. KLF4 binds to hTERT promoter in vitro. 50 Figure 15. KLF4 binds to hTERT promoter in vivo with transiently transfected with KLF4. 51 Figure 16. KLF4 binds to hTERT promoter in vivo. 52 Figure 17. hTERT expression decreased after knockdown of KLF4. 53 Figure 18. Effects of KLF4 gene knockdown on hESCs. 54 Figure 19. Repression of KLF4 expression induces hESC differentiation. 55 Figure 20. Repression of KLF4 expression induces hESC differentiation (continued). 56 Figure 21. KLF4 binds to hTERT promoter in hESs. 57 Figure 22. hTERT expression rescues KLF4 siRNA-induced hESC differentiation. 58 Figure 23. hTERT expression rescues KLF4 siRNA-induced hESC differentiation (continued). 59 Figure 24. KLF4 does not regulate AP activity. 60 Figure 25. KLF4 does not promote hTR expression. 61 8. References 62 | |
dc.language.iso | en | |
dc.title | 探討幹細胞中轉錄因子KLF4調控端粒酵素基因表現 | zh_TW |
dc.title | Study gene regulation of telomerase by transcription factor KLF4 in stem cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 王萬波(Won-Bo Wang),吳國瑞(Kou-Juey Wu),錢宗良(Chung-Liang Chien),張富雄(Fu-Hsiung Chang),李財坤(Tsai-Kun Li) | |
dc.subject.keyword | 端粒,端粒酵素,幹細胞,轉錄因子KLF4, | zh_TW |
dc.subject.keyword | Telomere,telomerase,stem cells,KLF4, | en |
dc.relation.page | 74 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-19 | |
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 | |
---|---|---|---|
ntu-99-1.pdf 目前未授權公開取用 | 3.58 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。