腫瘤易感基因TSG101，參與基因轉錄、細胞膜傳輸、細胞生長和分化之調控。在細胞中TSG101 表現量被嚴謹控制在一定範圍內，其缺乏或過度表現皆造成小鼠腫瘤之形成。本研究主要目的在探討TSG101 啟動子活性區之所在，並分析啟動子活性區上之轉錄因子結合位，對TSG101 啟動子功能之重要性。啟動子活性報導之研究結果顯示TSG101 基因近端啟動子活性區主要位在-1〜-436 區域。該區序列顯示其具有Sp1、MAZ、ETF 及ETS 等轉錄因子結合序列，為一典型不具TATA-box 之啟動子，符合其為管家基因之特性。本研究並發現DNA 甲基化，可抑制TSG101 啟動子報導活性，而甲基化抑制劑AzaC 之處理，則TSG101 蛋白表現上升，顯示TSG101 基因之表現會受到DNA 甲基化之調控。此外，本研究亦發現上游 -1280〜-1757區，可顯著提升啟動子在轉形細胞如COS-1 及甲狀腺癌ARO 及WRO 細胞中之啟動子報導活性，且其活性不受其方向性所影響，顯示此區域具有促進子(Enhancer)之特性。但該區在初代正常大鼠甲狀腺FRTL 細胞則不具此活性。此結果顯示在轉型細胞及正常細胞中，TSG101 基因啟動子活性調控有差異性，此點與前人報導在人類甲狀腺癌及乳癌檢體中有TSG101 過度表現之現象相符合。本研究並利用電泳膠體位移法，進一步證實Sp1與MAZ 確實會與含有該對應結合位序列之探針結合。進一步以定點突變方法，證實此兩結合位點，不論在轉型或初代甲狀腺細胞內之TSG101 啟動子報導活性為必需。但在涵蓋促進子之報導質體(-1〜-2647)之活性分析則發現，不論在轉型或初代甲狀腺細胞內中，Sp1 結合位點對TSG101 啟動子活性皆扮演正向調控角色，而MAZ 結合位在轉型細胞亦為正向調控角色，但在初代甲狀腺細胞中，則扮演負向調控角色。綜合以上結果，推測在轉型細胞中，Sp1 與MAZ 結合位及結合其上之Sp1 及MAZ 轉錄因子一起參與促進子上結合之活化因子之招募，而造成TSG101 啟動子活性之提升，而在初代甲狀腺細胞中MAZ 結合位則可能參與招募負向轉錄調控之抑制因子，而對TSG101 啟動子活性扮演負向調控之角色。

Tumor susceptibility gene, TSG101, participates in regulation of cellular functions such as gene transcription, vesicular trafficking, cell growth and differentiation. The steady-state level of TSG101 protein is kept in a narrow range. Deprivation or overexpression of TSG101 leads to neoplastic in mouse model. The purpose of this dissertation is to define the upstream promoter region of TSG101 and investigates the role of putative transcription factor binding sites reside in this promoter region. The results of promoter activity reporter assay indicated that TSG101 proximal promoter reside -1〜-436 region, Which contains binding site sequences for Sp1, MAZ , ETF and ETS transcription factors. It exhibits as a TATA-Less housekeeping type gene promoter. DNA methylation led to inhibition of TSG101 promoter reporter activity, while treatment with AzaC, a DNA methylation inhibitor, resulted in a dose-dependent elevation of TSG101 protein. The findings indicate that TSG101 promoter could be regulated by promoter DNA methylation. In addition, up-stream -1280〜-1757 region could function as an enhancer that orientation-independently increases TSG101 promoter activity in COS-1 transformed cells and thyroid carcinoma ARO and WRO cells. Interestingly, this region did not behave as an enhancer in primary rat thyroid FRTL cell. These results indicate TSG101 promoter could be regulated in normal and neoplastic thyroid cells, which corresponds to previous reports that TSG101 overexpression in thyroid and breast carcinoma specimens. We further demonstrated in vitro binding of Sp1 and MAZ transcription factors with electrophoretic mobility-shift assy (EMSA) assay by using probs with corresponding binding sequences. Experiments using mutant reporter constructs created by site-directed mutagenesis also demonstrated that both Sp1 and MAZ binding sites are essential for TSG101 promoter activity in transformed or primary thyroid cells. Whereas, reporter construct encompassing further upstream (-1～-2647) region showed differential promoter activities in transformed and primary thyroid cells. In these two type of cells, Sp1 binding site exhibits positive role in activation TSG101 promoter. However, MAZ played a positive role in transformed cell, but negative role in primary thyroid cells. Taken together, our results implied that in transformed cells, Sp1 and MAZ binding sites and their bound Sp1 and MAZ transcription factors together articipate in recruiting activators bound on enhancer to further stimulat TSG101 promoter activity. Whereas, in primary thyroid cells, MAZ binding site and presumably its bound MAZ transcription factor might function to recruit negative transcription regulator; hence, negatively regulate TSG101 promoter activity.

論文審定書---------------------------------------------i
致謝---------------------------------------------------ii
中文摘要------------------------------------------------iii
英文摘要------------------------------------------------------ v
文獻回顧--------------------------------------------------- 1
研究目的及設計---------------------------------------------- 13
材料與方法--------------------------------------------------16
第一部份TSG101啟動子( promoter) 與促進子(enhancer) 序列的確
認與分析--------------------------------------------------------------------16
第二部份TSG101 啟動子DNA甲基化後對其基因表現調控之影響--31
第三部份Sp1和MAZ與TSG101啟動子結合之分析--------------36
結果------------------------------------------------------------------------------- 46
第一部份TSG101啟動子( promoter) 與促進子(enhancer) 序列的確
認與分析 -----------------------------------------------------46
第二部份TSG101 啟動子DNA甲基化後對其基因表現調控之影響--49
第三部份Sp1和MAZ與TSG101啟動子結合之分析---------------------50
總結與討論----------------------------------------------------------------------- 57
第一部份TSG101啟動子( promoter) 與促進子(enhancer)序列的確認
與分析----------------------------------------------------------------------------57
第二部份TSG101 啟動子DNA甲基化後對其基因表現調控之影響--60
第三部份Sp1和MAZ與TSG101啟動子結合之分析-------------63
參考文獻------------------------------------------------------------------ 74
圖表-----------------------------------------------------------------85

Antequera, F., and Bird, A. P. (1993). Number of CpG-islands and genes in human and mouse. Proc Natl Acad Sci USA 90: 11995-11999.
Armstrong, S. A., Barry, D. A., Leggtt, R. W. and Mueller, C. R. (1997). Casein kinase II-mediated phosphorylation of the C-terminus of Sp1 decrease its DNA binding activity. J Biol Chem 272: 13489-13495.
Apt, D., Watts, R. M., Suske, G., and Bernard, H. U. (1996). Hight Sp1/Sp3 ratios in epithelial cells during epithelial differentiation and cellular transformation correlate with the activation of the HPV-16 promoter. Virology 224: 281-291.
Ashfield, R., Patel, A. J., Bossone, S. A., Brown, H., Campbell, R. D., Marcu, K. B., and Proudfoot, N. J. (1994). MAZ-dependent termination between closely spaced human complement gene. EMBO J 13: 5656-5667.
Babst, M., Odorizzi, G., Estepa, E. J., and Emr, S. D. (2000). Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23, both function in late endosomal trafficking. Traffic 1: 248-258.
Baylin, S. B., Herman, J. G., Graff, J. R., Vertion, P. M., and Issa, J. P. (1998). Alteration in DNA methylation: A fundamental aspect of neoplasia. Adv. Cancer Res 72: 141-196.
Bird, A. P. (1986). CpG-rich islands and the function of DNA methylation. Nature 321: 209-231.
Bossone, S. A., Asselin, C., Patel, A. J., and Marcu, K. B. (1992). MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. Proc Natl Acad Sci USA 89: 7452-7456.
Bennett, N. A., Pattillo, R. A., Lin, R. S., Hsieh, C. Y., Murphy, T. and Lyn, D. (2001). TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins. Cell Mol Biol 47: 1187-1193.
Carney, M. E., Maxwell, G. L., Lancaster, J. M., Gumbs, C., Marks, J., Berchuck, A., and Futreal, P. A. (1998). Aberrant splicing of the TSG101 tumor suppressor gene in human breast and ovarian cancers. J Soc Gynecol Investig 5: 281-285.
Chang, J. G., Su, T. H., Wei, H. J., Wang, J. C., Chen, Y. J., Chang, C. P., and Jeng, C. J. (1999). Analysis of TSG101 tumour susceptibility gene transcripts in cervical and endometrial cancers. Br J Cancer 79: 445-450.
Cheng, T. H., and Cohen, S. N. (2007). Human MDM2 isoforms tranalated differentially on constitutive versus p53-regulated transcripts have distinct functions in the p53/MDM2 and TSG101/MDM2 feedback control loops. Mol Cell Biol 27: 111-119.
Cieslik, K., Lee, C. M., Tang, J. l., and Wu, K. K. (1999). Transcriptional regulation of endothelial nitric-oxide synthase by an interaction between casein kinase 2 and protein phosphatase 2A. J Biol Chem 274: 34669-34675.
Colgan, J., and Manley, J. L. (1995). Cooperation between core promoter elements influences transcriptional activity in vivo. Proc Natl Acad Sci USA 92: 1955-1959.
Cooper, D. N., and Krawczak, M. (1989). Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes. Hum Genet 83: 181-188.
Courey, A. J., Holttzman, D. A., Jackson, S. P., and Tjian, R. (1989). Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell 59: 827-836.
Daniel, S., Zhang, S., Depaoli-Roah, A. A., and Kim, K. H. (1996). Dephoosphorylation of Sp1 by protein phosphatase 1 is involved in the glucose-rich activation motif. Cell 55: 887-889.
Demirov, D. G., Ono, A., Orenstein, J. M. and Freed, E. O. (2002). Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function. Proc Natl Acad Sci USA 99: 955-960.
Duncan, D. D., Stupakoff, A., Hedrick, S. M., Marcu, K. M., and Siu, G. (1995). A myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter. Mol cell Biol 15: 3179-3186.
Dynlacht, B. D., Hoey, T., and Tjian, R. (1991). Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell 66: 563-567.
Dynan, W. S., and Tjian, R. (1983). The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell 35: 79-87 .
Esteller, M., and Herman, J. G. (2002). Cancer as an epigenetic disease: DNA methylation and chromatin in human tumors. J. Pathol 196: 1-7.
Feng, G. H., Lih, C. J., and Cohen, S. N. (2000). TSG101 protein steady-state level is regulated posttranslationally by an evolutionarily conserved COOH-terminal sequence. Cancer Res 60: 1736-1741.
Felsenfeld, G. (1992). Chromatin as an essential part of the transcriptional mechanism. Nature 355: 219-224.
Fukuda, H., Noguchi, T., and Iritani, N. (1999). Transcriptional regulation of fatty acid synthase gene and ATP citrate-lyase gene by Sp1 and Sp3 in rat hepatocytes. FEBS 464: 113-117.
Gardier-Garden M., and Formmer M. (1987). CpG islands in verterbrate genomes. J Mol Biology 196: 261-282.
Garrus, J. E., von Schwedler, U. K., Pornillos, O. W., Morham, S. G., Zavitz, K. H., Wang, H. E., Wettstein, D. A., Stray, K. M., Cote, M., and Rich, R. L (2001). Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107: 55-65.
Gegonne, A., Bosselut, R., Bailly, R-A., and Ghysdael, J. (1993). Synergistic activation of the HTLV1 LTR ETS-responsive region by transcription factors Ets1 and Sp1. EMBO J 12: 1169-1178.
Gonzalog, M. L., Bender, C. M., You, E. H., and Glendening, J. M. (1997). Low frequency of p16/CDKN2A methylation in sporadic melanoma: comparative approaches for methylation analysis of primary tumor. Cancer Res 57: 5336-5347.
Han, K. K., and Martinage, A. (1992). Post-translational chemical modification of proteins. Int. J. Biochem 24: 19-28.
Her, S., Claycomb, R., Tai, T. C., and Wong, D. L. (2003). Regulation of the Rat phenylethanolamine N-methyltransferase gene by transcrikption factors Sp1 and MAZ. Mol Pharmacology. 64: 1180-1188.
Hiltunen, M. O., Alhonen, L., Koistinaho, J., Myohanen, S., Paakkonen, M., Marin, S., Kosma, V. M., and Janne, J. (1997). Hypermethylation of the colorectal carcinoma. Int J cancer 70: 644-648.
Hittelman, A. B., Burakov, D., Iniguez-Lluhi, J. A., Freedman, L. P., and Garabedian, M. J. (1999). Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. EMBO J 18: 5380-5388.
Izzo, M. W., Strachan, G. D., Stubbs, M. C., and Hall, D. J. (1999). Transcriptional repression from the c-myc P2 promoter by the Zinc finger protein ZF87/MAZ. J Biol Chem 274: 19498-19506.
Iguchi-Ariga, S. M., and Schaffner, W. (1989). CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev 3: 612-619.
Innocente, S. A., and Lee, J. M. (2005). p73 is a p53-independent, Sp1-dependent repressor of cyclin B1 transcription. Biochem Biophys. Res Comm. 329: 713-718.
Karlseder, J., Rotheneder, H., and Wintersberger, E. (1996). Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol Cell Biol. 16: 1659-1667.
Kadonaga, J. T., Carner, K. R., Masiarz, F. R., and Tjian, R. (1987). Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell 51: 1070-1090.
Katzmann, D. J., Babst. M., and Emr, S. D. (2001). Ubiqutitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106: 145-155.
Karlseder, J. T., Courey, A. J., Ladika, J., and Tjian, R. (1988). Distinct regions of Sp1 modulate DNA binding and transcriptionl activation. Science 242: 1566-1570.
Kelley, K. M., Wang, H., and Ratnam, M. (2003). Dual regulation of ets-activated gene expression by SP1. Gene 307: 87-97.
Koonin, E. V., and Abagyan, R. A. (1997). TSG101 may be the prototype of a class of dominant negative ubiquitin regulators. Nat Genet 16: 330-331.
Kumar, A. P., and Butler, A. P. (1998). Serum responsive gene expression mediated by Sp1. Biochem Biophy Res Comm 252: 517-523.
Lee, J. S., Galvin, K .M., and Shi, Y. (1993). Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc Natl Acad Sci USA 90: 6145-6149.
Lee, M. P., and Feinberg, A. P. ( 1997). Aberrant splicing but not mutations of TSG101 in human breast cancer. Cancer Res 57: 3131-3134.
Li, L., and Cohen, S. N. (1996). Tsg101: a novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells. Cell 85: 319-329.
Li, L., Li, X., Francke, U., and Cohen, S. N. (1997). The TSG101 tumor susceptibility gene is located in chromosome 11 band p15 and is mutated in human breast cancer. Cell 88: 143-154.
Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nature Reviews 3: 662-673.
Li, L., Liao, J., Ruland, J., Mak, T. W., and Cohen, S. N. (2001). A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control. Proc Natl Acad Sci USA 98: 1619-1624.
Lin, P. M., Liu, T. C., Chang, J. G., Chen, T. P., and Lin, S. F. (1998). Aberrant TSG101 transcripts in acute myeloid leukaemia. Br J Haematol 102: 753-758.
Liu, R. T., Huang, C. C., You, H. L., Chou, F. F., Hu, C. C., Chao, F. P., Chen, C. M., and Cheng, J. T. (2002). Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinoma. Oncogene 21: 4830-4837.
Lopez-Rodriguez, C., Botella, L., and Corbi, A. L. (1997). CCAAT-enhancer- Binding protein (C/EBP) regulate the tissue specific activity of the CD11c intrgrin gene promoter through functional interactions with Sp1 proteins. J Biol Chem 272: 29120-29126.
Majumder, S., Zhao, Z., Kaneko, K., and Dpamphilis, M. (1997). Developmental acquisition of enhancer function requires aunique coactivator activity. EMBO J 16: 1721-1731.
Maniatis, T., Goodbourn, S., and Fischer., J. A. (1987). Regulation of inducible and tissue-specific dene expression. Science 236: 1237-45.
Marin, M,. Goodbourn, S., Fischer, J. A., Visser, P., Grosveld, F., and philipsen, S. (1997). Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Cell 89: 619-628.
Martin, D-I. K. (2001). Transcriptional enhancers- on/off gene regulation as an adaptation to silencing in higher eukaryotic nuclei. Trends in Genetics 17: 444-448.
Mastrangelo, I. A., Courey, A. J., Wall, J. S., Jackson, S. P., and Hough, P. V. (1991). DNA looping and Sp1 multimer links: a mechanism for transcriptional synergism and enhancement. Proc Natl Acad Sci USA 88: 5670-5674.
Maucuer, A., Camonis, J. H., and Sobel, A. (1995). Stathmin interaction with a putative kinase and coiled-coil-forming protein domains. Proc Natl Acad Sci USA 92: 3100-3104.
McIver, B., Grebe, S. k., Wang, L., Hay, I. D., Yokomizo, a., Liu, W., Goellner, J. R., Grant, C. S., Smith, D. I., and Eberhardt, N. L. (2000). FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance. Clin Endocrinol 52: 749-757.
McDowell, T. L., Symons, J. A., and Duff, G. W. (2005). Human interleukin-1 gene expression is regulated by Sp1 and a transcriptional repressor. Cytokine 1-12.
McKnight, S., and Tjian, R. (1986). Transcriptional selectivity of viral genes in mammalian cells. Cell 46: 795-805.
Mee, S. L., Fromigue, and O., Marie, P. J. (2005). Sp1/Sp3 and the myeloid zinc finger gene MZF1 regulate the human N-cadherin promoter in osteoblasts. Exp Cell Res 302: 129-142.
Merchant, J. L., Du, M., and Todisco, A. (1999) Sp1 phosphorylation by Erk2 stimulates DNA binding. Biochem Biophys Res Comm 254: 454-461.
Momparler, R. L., and Bovenzi, V. (2000). DNA methylation and cancer. J. Cell. Physiol 183: 145-154.
Moyret-Lalle, C., Duriez, C., Van Kerckhove, J., gilbert, C., Wang, Q., and Puisieux, A. (2001). p53 induction prevents accumulation of aberrant transcripts in cancer cells. Cancer Res 61: 486-488.
Nan, X., Campoy, F. J., and Bird, A. (1998). MeCP2 is a transcriptional repressor with abundant binding sites ingenomic chromatin. Cell 88: 471-481.
Nakao, M. (2001). Epigenetics: interaction of DNA methylation and chromatin. Gene 278: 25-31.
Ng, H. H., Zhang, Y., Hendrich, B., Johnson, C. A., Turner, B. M., Erdjume-Bromage, H., Tempst,g P., Reinberg, D., and Bird, A. (1999). MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nature Gene 23: 58-61.
Noe, V., Alemany, C., Nicolas, M., and Ciudad, C. J. (2001). Sp1 involvement in the 4bata-phorbol 12-myristate 13-acetate (TPA)-mediated increase in resistance to methotrexate in Chinese hamster ovary cells. Eur J Biochem 268: 3163-3173.
Noti, J. D., Reinemann, B. C., and Petrus, M. N. (1996). Sp1 binds two sittes in the CD11c promoter in vivo specifically in myeloid cells and cooperates with AP1 to activate transcription. Mol Cell Biol 16: 2940-2950.
Oh, H., Mammucari., C., Nenci, A., Cabodi, S., Cohen, S. N., and Dotto, G. P. (2002). Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1). Proc Natl Acad Sci USA 99: 5430-5435.
Ogra, Y., Suzuki, K., Gong, P., Otsuka, F., and Koizumi, S. (2001). Negativeregulatory role of Sp1 in metal responsive element-mediated transcriptional activation. J Biol Chem 276: 16534-16539.
Okamoto, S-I., Sherman, K., Bai, G., and Lipton, S. A. (2002). Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differential. Mol brain Res 107: 89-96.
Paranjape, S. M., Kamakaka, R. T., and Kadonaga, J. T. (1994). Role of chromatin structure in the regulation of transcription by RNA polymeraseⅡ. Ann Rev Biochem 63: 2497-3704.
Parks, T. D., and Karpen, G. H. (1996). The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J Biol Chem 271: 4417-4430.
Parks, T. D., and Karpen, G. H. (1997). Activation of the adenovirus major late promoter by transcription factor MAZ and Sp1. J. Virol 71: 9600-9607.
Perkins, N. D., agranoff, A. B., pascal, E., and Nabel, G. J. (1994). An interaction between the DNA-binding domains of RelA (p65) and Sp1 mediates human immunodeficiency virus gene activation. Mol Cell Biol. 14: 6570-6583.
Prendergast, G. C., and Ziff, E. B. (1991). Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science 251: 186-189.
Pugh, B. F., and Tjian, R. (1990). Mechanism of transcriptional activation by Sp1: Evidence for coactivators. Cell 61: 1187-1197.
Pondel, M. D., and Partington, G. A. (2003). Tissue-specific activity of the proximal human calcitonin receptor promoter is mediated by Sp1 an epigenetic phenomenon. FEBS Lett 554: 433-438.
Reeve, A. E., Sih, S. A., Raizis, A. M., and Feinberg, A. P. (1989). Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms’ tumor cells. Mol Cell Biol 9: 1799-1803.
Ruland, J. Sirard, C., Elia, A., Macpherson, D., Wakeham, A., Li, L., Dela Pompa, J. L., Cohen, S. N., and Mak, T. W. (2001). p53 accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101. Proc Natl Acad Sci USA 98: 859-1864.
Robertson, K. D., and Jones, P. A. (2000). DNA methylation : past, present and future directions. Carcinogenesis 21: 461-467.
Roerder, R. G. (1991). The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci 16: 402-408 .
Ryu, S., Zhou, S., Ladurner, A. G., and Tjian, R. (1999). The transcriptional cofactor complex CRSP is required for activity of enhancer-binding protein Sp1. Nature 397: 446-450.
Saffer, J. D., Jackson, S. P., and Annarella, M. B. (1991). Developmental expression of Sp1 in the mouse. Mol Cell Biol 11: 2189-2199.
Seto, E., Lewis, B., and Shenk, T. (1993). Interaction between transcription factors Sp1 and YY1. Nature 365: 462-464.
Song, J., Murakami, H., Tsutsui, H., Tang, X., Matsumura, M., Itakura, K., Kanazawa, I.., Sun, K., and Yokoyama, K. K. (1998). Genomic organization and expression of a human gene for Myc-associated zinc finger protein (MAZ). J Biol Chem 273: 20603-20614.
Song, J., Ugai, H., Ogawa, K., Wang, Y., Sarai, A., and Yokoyama, K. K. (2001 a). Two consecutive zinc fingers in Sp1 and in Maz aes essential for interactions with cis-elements. J Biol Chem 276: 30249-30434.
Song, J., Ugai, H., kankzawa, I., Sun, K., and Yokoyama, K. K. (2001 b). Independent repression of a GC-rich housekeeping gene by Sp1 and MAZ involves the same cis-elements. J Biol Chem 23: 19897-19904.
Steiner, P., Barnes, D. M., Harris, W. X., Cohen, S. N., and Balk, S. P. (1999). Absence of rearrengements in the tumor susceptibility gene TSG101 in human breast cancer. Nat Genet 16: 332-333.
Su, W., Jackson, S., Tjian, R., and Echols, H. (1991). DNA looping between site for transcriptional activator: self-association of-bound Sp1. Cene Dev 5: 820-826.
Suske, K. (1999). The Sp-family of transcription factors. Gene 238: 291-300.
Suehiro, T., Kaneda, T., Ikeda, Y., Arii, K., Kumon, Y., and Hashimoto, K. (2004). Regulation of human glucocorticoid receptor gene transcription by Sp1 and p53. Mole Cell Endocrinol 222: 33-40.
Sun, Z., Pan, J., Hope, W. X., Cohen, S. N., and Balk, S. P. (1999). Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300. Cancer 86: 689-696.
Tate, P. H., and Bird, A. P. (1993). Effects of DNA methylation on DNA-binding proteins and gene expression. Curr Opin Genet Dev 3: 226-231.
Timothy, A. R., and Cook, G. J. (1998). PET scanning in clinical oncology. Ann Oncol 9, 353-355. Biochem Biophy Res Comm 252: 517-523.
Tsutsui, H., Geltinger, C., Murata, T., Itakura, K., Wada, T., Handa, H., and Yokoyama, K. (1999). The DNA-binding and transcriptional activities of MAZ, a Myc associated zinc finger protein, are regulated by casein kinase II. Biochem Biophys Res Comm. 262: 198-205.
Turner, B. M., and O’Neill, L. P. (1995) Histone acetylation in chromatin and chromosomes. Semin. Cell Biol 6: 229-236.
Wang, N. M., Chang, J. G., Liu, T. C., Lin, S. F., Peng, C. T., Tsai, F. J., and Tsai, C. H. (2000). Aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 genes in normal peripheral mononuclear cells. Int J Oncol 16: 75-80.
Weitzel, J. N., Patel, J., Smith, D. M., Googman, A., Safaii, H., and Ball, H. G. (1994). Molecular genetic changes associated with ovarian cancer. Gynecol Oncol 55: 245-252.
Willeke, F., Ridder, R., Bork, P., Klase, R., Mechtersheimer, G., Schwarzbach, M., Zimmer, D., Kloor, M., Lehent, T., Herfarth, C., and von Knebel Doeberitz, M. (1998). Identical variant TSG101 transcripts in soft tissue sarcomas and various non-neoplastic tissues. Mol Carcinog 23: 195-200.
Williams, LJS., and Abou-Samra, A. B. (2000). The transcription factors SP1 and MAZ regulate expression of the parathyroid hormonr/parathyroid hormone-related peptide receptor gene. J Mol Endo 25, 309-319.
Yoder, J. A., Walsh, C. P., and Bestor, T. H. (1997). Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13: 335-340.
You, H. L., Eng, H. L., Hsu, S. F., Chen, C. M., Ye, W. T., Huang, M. Y., Hung, M. Y., Baer, R., and Cheng, J. T. (2007). A PCK-Sp1 signaling induces early differentiation of human keratinocytes through upregulation of TSG101. Cell Signal 19: 1201-1211.
Yu, F., Thiesen J., and Stratling W. H. (2000) Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2. Nucleic Acids Res 28: 2201-2206.
Xie, W., Li, L., and Cohen, S. N. (1998). Cell cycle-dependent subcellular localization of the TSG101 protein and mitotic and nuclear abnormalities associated with TSG101 deficiency. Proc Natl Acad Sci USA 95:1595-1600.
Zhong, Q., Cheng, Y., Jones, D., and Lee, W. H. (1998). Perturbation of TSG101 protein affects cell cycle progression. Cancer Res 58: 2699-2702.
Zhu, G., Gilchrist, R., Borley, N., Chng, H. W., Morgan, Morgan, M., Marshall, J. F., Camplejohn, R. S., Muir, G. H., and Hart, I. R. (2004). Reduction of TSG101 protetein has a negative impact on tumor cell growth. Int J Cancer 109: 541-547.
趙芳苹. (2001). 甲狀腺腫瘤檢體中TSG101與 RET 基因表現之研究.國立中山大學生物科學研究所碩士論文.
黃曼怡. (2005). ETF及ETS-1轉錄因子結合位點突變對TSG101啟動子活性影響之探討. 國立中山大學生物科學研究所碩士論文.