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研究生:尤慧玲
研究生(外文):Huey-Ling You
論文名稱:腫瘤易感基因TSG101在角質細胞分化功能及其在p16INK4a啟動子染色質重塑之角色探討
論文名稱(外文):The roles of tumor susceptibility gene 101 in keratinocyte differentiation and chromatin remodeling of p16INK4a promotor
指導教授:陳錦翠
指導教授(外文):Jiin-Tsuey Cheng
學位類別:博士
校院名稱:國立中山大學
系所名稱:生物科學系研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:112
中文關鍵詞:腫瘤易感基因角質細胞分化p16INK4a啟動子
外文關鍵詞:p16INK4a promotordifferentiationTSG101keratinocyte
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腫瘤易感基因TSG101具有調控基因表現、囊泡運輸及細胞生長與分化等多項生物功能,然而對於調控TSG101基因功能之訊號傳遞路徑並不清楚。根據我們的研究成果發現,不論是在人類正常表皮或是人工培養之類表皮組織中,TSG101之表現強度與分化狀態成正相關;同時我們也發現,在鈣誘導角質細胞分化之過程中,若抑制TSG101在細胞內之表現量,則會同步抑制分化作用之繼續進行,顯示TSG101在分化過程當中扮演著非常重要之角色。另外,藉由下列之實驗結果亦證實了調控TSG101表現之訊號傳遞路徑與 PKC有關;第一、PKC活化劑TPA可正向調控TSG101及keratin 10之表現,第二、同時添加 TPA及PKC抑制劑GF 109203X,能有效阻斷 TPA誘導之TSG101及keratin 10表現。已有研究報導指出TSG101啟動子區域具有Sp1結合位點,我們的分析結果顯示鈣與TPA會刺激Sp1之磷酸化及其轉錄活性,同時也會促進TSG101啟動子之活性,但此作用並不會發生在Sp1結合位點有突變之TSG101啟動子。而GF 109203X阻斷鈣與TPA之作用,同樣也可以阻斷TSG101之啟動子活性,顯示其為PKC依賴性步驟;綜合上述結果可推論,PKC-Sp1之訊號傳遞可藉由促進TSG101之表現而啟動角質細胞之早期分化程序。抑制小鼠細胞內tsg101之功能表現會導致小鼠產生腫瘤,說明了tsg101具有腫瘤抑制劑之功能。然而很多針對人體腫瘤組織之分析,或是細胞特異性tsg101基因剔除小鼠之實驗卻得到不一致之結果。本研究之另一結果發現人類頭頸部鱗狀上皮癌組織之TSG101蛋白質表現情形與p16INK4a及acetylated-histone H4之表現呈負相關(N=98, p<0.001)。因此,進一步使用人類喉癌上皮細胞HEp-2調整改變細胞內TSG101表現量,實驗結果發現TSG101會逆向調控p16INK4a在細胞內之mRNA及蛋白質表現情形。藉由染色質免疫沉澱方法(ChIP)也證實了,TSG101會降低p16INK4a 啟動子區染色質上結合之acetylated-histone H4量,而抑制p16INK4a 啟動子活性。此外,共軛顯微鏡觀察及免疫共沉澱分析之結果皆顯示,TSG101會與HDAC1及SUMO-1在細胞核內形成複合體,而TSG101會呈劑量效應地促進細胞中HDAC1受SUMO修飾之作用,進而提昇其酵素活性;綜合以上實驗結果可知,我們的實驗設計首先證明了TSG101可以促進HDAC1之SUMO-1修飾作用,進而逆向調控p16INK4a之表現,此機制可能為造成頭頸部腫瘤鱗狀上皮癌發展過程中,p16INK4a表現量下降之另一重要原因,並為TSG101參與頭頸部腫瘤進展時,p16INK4a基因表現之epigenetic調控提供有力證據。
Tumor Susceptibility Gene 101, TSG101, exhibits multiple biological functions including the regulation of gene transcription, vesicular trafficking, cellular growth and differentiation. However, the signals involve in the regulation of TSG101 gene functions are unclear. In this present study, we observed congruous TSG101 up-regulation and the differentiation status of keratinocyte in both human foreskin tissue and reconstructed organotypic skin culture. In addition, we found an essential and downstream role of TSG101 in calcium-induced early keratinocyte differentiation since TSG101 siRNA inhibits this process. Our results also indicate a PKC-dependent mechanism is involved based on the following findings. First, a PKC agonist, TPA up-regulates TSG101 and keratin 10 under low calcium condition. Second, co-treatment of keratinocytes with GF 109203X, a PKC inhibitor, blocks TPA-induced TSG101 and keratin 10 up-regulation. Previous report indicates TSG101 gene exhibits a TATA-less and Sp1-containing promoter. Our analysis further shows that both calcium and TPA stimulate phosphorylation of Sp1 and the corresponding TSG101 wild type promoter activity, but not the activity of Sp1 site mutant TSG101 promoter. The co-treatment with GF 109203X blocks the above effects of calcium and TPA, implying that this is a PKC signaling-dependent process. Taken together, these data suggest a PKC-Sp1 signaling is involved in early differentiation switch of keratinocyte through up-regulation of TSG101. Functional inactivation experiment indicates that tsg101 is a tumor suppressor in mouse model. However, many studies using human tumor specimens or conditional knockout mouse give discrepant and contradictive results. Therefore, the role of TSG101 in human cancer remains illusive. Here we demonstrate an inverse correlation between TSG101 and p16INK4a or acetylated- histone H4 protein expression profiles in human head and neck squamous cell carcinomas (HNSCC) (N=98, p<0.001). Using conditioned human HEp2 cells, we confirm that TSG101 negatively modulates p16INK4a expression. Chromatin immunoprecipitation and the subsequent PCR analysis reveal that TSG101 dose-dependently decreases the amount of acetylated histone H4-associated chromatin on p16INK4a promoter. In addition, TSG101 interacts and colocalizes with HDAC1 and SUMO-1 in the nucleus. Furthermore, TSG101 confers a dose-dependent effect on promoting HDAC1 SUMOylation, hence its activity. Taken together, our data demonstrate for the first time that TSG101 can promote SUMO-1 modification of HDAC1, which impacts on down-regulation of p16INK4a gene expression, providing evidence whereby TSG101 might participate in the epigenetic silencing of p16INK4a during the development of HNSCC.
中文總摘要------------------------------------------------ 1
英文總摘要------------------------------------------------ 3
縮寫文字對照表-------------------------------------------- 5
第一章 總緒論
一、腫瘤易感基因TSG101與人類癌症之相關性-------- 8

二、TSG101基因位置與蛋白質功能結構-------------- 8

三、TSG101與細胞週期之關係--------------------- 14
四、角質細胞分化過程中TSG101與p21 waf1/cip1之交互作用--- 18
五、研究方向與目的----------------------------- 20

第二章 角質細胞分化過程中TSG101之功能角色
前言--------------- --------------------------- 23
實驗材料與方法--------------------------------- 25
實驗結果--------------------------------------- 33
結果討論--------------------------------------- 37
圖表------------------------------------------- 40
第三章 TSG101在p16INK4a啟動子染色質重塑之角色探討
前言------------------------------------------- 53
實驗材料與方法--------------------------------- 55
實驗結果--------------------------------------- 67
結果討論--------------------------------------- 72
圖表------------------------------------------- 76
綜合討論------------------------------------------------- 94
參考文獻------------------------------------------------- 96
1.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.
2.Trink, B., Pai, S. I., Spunt, S. L., Raman, V., Cairns, P., Jen, J., Gabrielson, E., Sukumar, S., and Sidransky, D. (1998) Absence of TSG101 transcript abnormalities in human cancers. Oncogene 16: 2815-2818.
3.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.
4.Sun, Z., Pan, J., Bubley, G., and Balk, S. P. (1997) Frequent abnormalities of TSG101 transcripts in human prostate cancer. Oncogene 15: 3121-3125.
5.Gayther, S. A., Barski, P., Batley, S. J., Li, L., de Foy, K. A., Cohen, S. N., Ponder, B. A., and Caldas, C. (1997) Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours. Oncogene 15: 2119-2126.
6.Lee, M. P., and Feinberg, A. P. (1997) Aberrant splicing but not mutations of TSG101 in human breast cancer. Cancer Res 57: 3131-3134.
7.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.
8.Lo, Y. F., Chen, T. C., Chen, S. C., and Chao, C. C. (2000) Aberrant expression of TSG101 in Taiwan Chinese breast cancer. Breast Cancer Res Treat 60: 259-266.
9.Turpin, E., Dalle, B., de Roquancourt, A., Plassa, L. F., Marty, M., Janin, A., Beuzard, Y., and de The, H. (1999) Stress-induced aberrant splicing of TSG101: association to high tumor grade and p53 status in breast cancers. Oncogene 18: 7834-7837.
10.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.
11.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.
12.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 carcinomas. Oncogene 21: 4830-4837.
13.Kinyamu, H. K., Chen, J., and Archer, T. K. (2005) Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors. J Mol Endocrinol 34: 281-297.
14.Yew, P. R. (2001) Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators. J Cell Physiol 187: 1-10.
15.Hansen, D. V., Hsu, J. Y., Kaiser, B. K., Jackson, P. K., and Eldridge, A. G. (2002) Control of the centriole and centrosome cycles by ubiquitination enzymes. Oncogene 21: 6209-6221.
16.VerPlank, L., Bouamr, F., LaGrassa, T. J., Agresta, B., Kikonyogo, A., Leis, J., and Carter, C. A. (2001) Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55(Gag). Proc Natl Acad Sci U S A 98: 7724-7729.
17.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 U S A 98: 1619-1624.
18.Verger, A., Perdomo, J., and Crossley, M. (2003) Modification with SUMO. A role in transcriptional regulation. EMBO Rep 4: 137-142.
19.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., Rich, R. L., Myszka, D. G., and Sundquist, W. I. (2001) Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107: 55-65.
20.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 U S A 92: 3100-3104.
21.Babst, M., Odorizzi, G., Estepa, E. J., and Emr, S. D. (2000) Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. Traffic 1: 248-258.
22.Bishop, N., Horman, A., and Woodman, P. (2002) Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol 157: 91-101.
23.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.
24.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.
25.Rountree, M. R., Bachman, K. E., and Baylin, S. B. (2000) DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet 25: 269-277.
26.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.
27.Sherr, C. J. (1993) Mammalian G1 cyclins. Cell 73: 1059-1065.
28.Sherr, C. J., and Roberts, J. M. (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9: 1149-1163.
29.Sherr, C. J. (1995) Mammalian G1 cyclins and cell cycle progression. Proc Assoc Am Physicians 107: 181-186.
30.Elledge, S. J. (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274: 1664-1672.
31.Sclafani, R. A., and Schauer, I. E. (1996) Cell cycle control and cancer: lessons from lung cancer. J Investig Dermatol Symp Proc 1: 123-127.
32.Sclafani, R. A. (1996) Cyclin dependent kinase activating kinases. Curr Opin Cell Biol 8: 788-794.
33.Amundson, S. A., Myers, T. G., and Fornace, A. J., Jr. (1998) Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress. Oncogene 17: 3287-3299.
34.Lakin, N. D., and Jackson, S. P. (1999) Regulation of p53 in response to DNA damage. Oncogene 18: 7644-7655.
35.Szemraj, J., Rozponczyk, E., Bartkowiak, J., Greger, J., and Oszajca, K. (2005) [Significance of MDM2 protein in the cell cycle]. Postepy Biochem 51: 44-51.
36.Sheikh, M. S., Chen, Y. Q., Smith, M. L., and Fornace, A. J., Jr. (1997) Role of p21Waf1/Cip1/Sdi1 in cell death and DNA repair as studied using a tetracycline-inducible system in p53-deficient cells. Oncogene 14: 1875-1882.
37.Zhang, H., Hannon, G. J., Casso, D., and Beach, D. (1994) p21 is a component of active cell cycle kinases. Cold Spring Harb Symp Quant Biol 59: 21-29.
38.Li, R., Waga, S., Hannon, G. J., Beach, D., and Stillman, B. (1994) Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature 371: 534-537.
39.Zhang, H., Hannon, G. J., and Beach, D. (1994) p21-containing cyclin kinases exist in both active and inactive states. Genes Dev 8: 1750-1758.
40.Ito, A., Kawaguchi, Y., Lai, C. H., Kovacs, J. J., Higashimoto, Y., Appella, E., and Yao, T. P. (2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. Embo J 21: 6236-6245.
41.Zhao, Y., Lu, S., Wu, L., Chai, G., Wang, H., Chen, Y., Sun, J., Yu, Y., Zhou, W., Zheng, Q., Wu, M., Otterson, G. A., and Zhu, W. G. (2006) Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1). Mol Cell Biol 26: 2782-2790.
42.Le Frere-Belda, M. A., Gil Diez de Medina, S., Daher, A., Martin, N., Albaud, B., Heudes, D., Abbou, C. C., Thiery, J. P., Zafrani, E. S., Radvanyi, F., and Chopin, D. (2004) Profiles of the 2 INK4a gene products, p16 and p14ARF, in human reference urothelium and bladder carcinomas, according to pRb and p53 protein status. Hum Pathol 35: 817-824.
43.Bulten, J., van der Avoort, I. A., Melchers, W. J., Massuger, L. F., Grefte, J. M., Hanselaar, A. G., and de Wilde, P. C. (2006) p14(ARF) and p16(INK4A), two products of the same gene, are differently expressed in cervical intraepithelial neoplasia. Gynecol Oncol
44.Ivanchuk, S. M., Mondal, S., Dirks, P. B., and Rutka, J. T. (2001) The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth. J Neurooncol 51: 219-229.
45.Yamasaki, L. (2003) Role of the RB tumor suppressor in cancer. Cancer Treat Res 115: 209-239.
46.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 U S A 95: 1595-1600.
47.Ruland, J., Sirard, C., Elia, A., MacPherson, D., Wakeham, A., Li, L., de la 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 U S A 98: 1859-1864.
48.Grossman, S. R., Perez, M., Kung, A. L., Joseph, M., Mansur, C., Xiao, Z. X., Kumar, S., Howley, P. M., and Livingston, D. M. (1998) p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol Cell 2: 405-415.
49.Thomas, A., and White, E. (1998) Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53 apoptotic function. Genes Dev 12: 1975-1985.
50.Todd, C., and Reynolds, N. J. (1998) Up-regulation of p21WAF1 by phorbol ester and calcium in human keratinocytes through a protein kinase C-dependent pathway. Am J Pathol 153: 39-45.
51.Martinez, L. A., Chen, Y., Fischer, S. M., and Conti, C. J. (1999) Coordinated changes in cell cycle machinery occur during keratinocyte terminal differentiation. Oncogene 18: 397-406.
52.Di Cunto, F., Topley, G., Calautti, E., Hsiao, J., Ong, L., Seth, P. K., and Dotto, G. P. (1998) Inhibitory function of p21Cip1/WAF1 in differentiation of primary mouse keratinocytes independent of cell cycle control. Science 280: 1069-1072.
53.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 U S A 99: 5430-5435.
54.Denning, M. F. (2004) Epidermal keratinocytes: regulation of multiple cell phenotypes by multiple protein kinase C isoforms. Int J Biochem Cell Biol 36: 1141-1146.
55.Herman, J. G., Merlo, A., Mao, L., Lapidus, R. G., Issa, J. P., Davidson, N. E., Sidransky, D., and Baylin, S. B. (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 55: 4525-4530.
56.Reed, A. L., Califano, J., Cairns, P., Westra, W. H., Jones, R. M., Koch, W., Ahrendt, S., Eby, Y., Sewell, D., Nawroz, H., Bartek, J., and Sidransky, D. (1996) High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res 56: 3630-3633.
57.Kashiwagi, M., Ohba, M., Chida, K., and Kuroki, T. (2002) Protein kinase C eta (PKC eta): its involvement in keratinocyte differentiation. J Biochem (Tokyo) 132: 853-857.
58.Missero, C., Di Cunto, F., Kiyokawa, H., Koff, A., and Dotto, G. P. (1996) The absence of p21Cip1/WAF1 alters keratinocyte growth and differentiation and promotes ras-tumor progression. Genes Dev 10: 3065-3075.
59.Missero, C., Calautti, E., Eckner, R., Chin, J., Tsai, L. H., Livingston, D. M., and Dotto, G. P. (1995) Involvement of the cell-cycle inhibitor Cip1/WAF1 and the E1A-associated p300 protein in terminal differentiation. Proc Natl Acad Sci U S A 92: 5451-5455.
60.Grana, X., Garriga, J., and Mayol, X. (1998) Role of the retinoblastoma protein family, pRB, p107 and p130 in the negative control of cell growth. Oncogene 17: 3365-3383.
61.Liao, W. T., Chang, K. L., Yu, C. L., Chen, G. S., Chang, L. W., and Yu, H. S. (2004) Arsenic induces human keratinocyte apoptosis by the FAS/FAS ligand pathway, which correlates with alterations in nuclear factor-kappa B and activator protein-1 activity. J Invest Dermatol 122: 125-129.
62.Ponec, M., Boelsma, E., Gibbs, S., and Mommaas, M. (2002) Characterization of reconstructed skin models. Skin Pharmacol Appl Skin Physiol 15 Suppl 1: 4-17.
63.Mehul, B., Asselineau, D., Bernard, D., Leclaire, J., Regnier, M., Schmidt, R., and Bernerd, F. (2004) Gene expression profiles of three different models of reconstructed human epidermis and classical cultures of keratinocytes using cDNA arrays. Arch Dermatol Res 296: 145-156.
64.Herson, M. R., Mathor, M. B., Altran, S., Capelozzi, V. L., and Ferreira, M. C. (2001) In vitro construction of a potential skin substitute through direct human keratinocyte plating onto decellularized glycerol-preserved allodermis. Artif Organs 25: 901-906.
65.Khavari, P. A. (2006) Modelling cancer in human skin tissue. Nat Rev Cancer 6: 270-280.
66.Fuchs, E., and Green, H. (1979) Multiple keratins of cultured human epidermal cells are translated from different mRNA molecules. Cell 17: 573-582.
67.Roop, D. R., Krieg, T. M., Mehrel, T., Cheng, C. K., and Yuspa, S. H. (1988) Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis. Cancer Res 48: 3245-3252.
68.Burgdorf, S., Leister, P., and Scheidtmann, K. H. (2004) TSG101 interacts with apoptosis-antagonizing transcription factor and enhances androgen receptor-mediated transcription by promoting its monoubiquitination. J Biol Chem 279: 17524-17534.
69.Hennings, H., Michael, D., Cheng, C., Steinert, P., Holbrook, K., and Yuspa, S. H. (1980) Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell 19: 245-254.
70.Denning, M. F., Dlugosz, A. A., Williams, E. K., Szallasi, Z., Blumberg, P. M., and Yuspa, S. H. (1995) Specific protein kinase C isozymes mediate the induction of keratinocyte differentiation markers by calcium. Cell Growth Differ 6: 149-157.
71.Wagner, K. U., Dierisseau, P., Rucker, E. B., 3rd, Robinson, G. W., and Hennighausen, L. (1998) Genomic architecture and transcriptional activation of the mouse and human tumor susceptibility gene TSG101: common types of shorter transcripts are true alternative splice variants. Oncogene 17: 2761-2770.
72.Apt, D., Watts, R. M., Suske, G., and Bernard, H. U. (1996) High 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.
73.Noe, V., Alemany, C., Nicolas, M., and Ciudad, C. J. (2001) Sp1 involvement in the 4beta-phorbol 12-myristate 13-acetate (TPA)-mediated increase in resistance to methotrexate in Chinese hamster ovary cells. Eur J Biochem 268: 3163-3173.
74.Goldberg, H. I., Lockwood, S. A., Wyatt, S. W., and Crossett, L. S. (1994) Trends and differentials in mortality from cancers of the oral cavity and pharynx in the United States, 1973-1987. Cancer 74: 565-572.
75.Fan, C. Y. (2001) Genetic alterations in head and neck cancer: interactions among environmental carcinogens, cell cycle control, and host DNA repair. Curr Oncol Rep 3: 66-71.
76.Thomas, G. R., Nadiminti, H., and Regalado, J. (2005) Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol 86: 347-363.
77.Chin, D., Boyle, G. M., Williams, R. M., Ferguson, K., Pandeya, N., Pedley, J., Campbell, C. M., Theile, D. R., Parsons, P. G., and Coman, W. B. (2005) Novel markers for poor prognosis in head and neck cancer. Int J Cancer 113: 789-797.
78.Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K., and Carson, D. A. (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368: 753-756.
79.Sanchez-Cespedes, M., Esteller, M., Wu, L., Nawroz-Danish, H., Yoo, G. H., Koch, W. M., Jen, J., Herman, J. G., and Sidransky, D. (2000) Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res 60: 892-895.
80.Bartkova, J., Lukas, J., Guldberg, P., Alsner, J., Kirkin, A. F., Zeuthen, J., and Bartek, J. (1996) The p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis. Cancer Res 56: 5475-5483.
81.Nilsson, K., Svensson, S., and Landberg, G. (2004) Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior. Mod Pathol 17: 1464-1474.
82.Villar-Garea, A., and Esteller, M. (2004) Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int J Cancer 112: 171-178.
83.Toh, Y., Yamamoto, M., Endo, K., Ikeda, Y., Baba, H., Kohnoe, S., Yonemasu, H., Hachitanda, Y., Okamura, T., and Sugimachi, K. (2003) Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma. Oncol Rep 10: 333-338.
84.Zhu, G., Reynolds, L., Crnogorac-Jurcevic, T., Gillett, C. E., Dublin, E. A., Marshall, J. F., Barnes, D., D''Arrigo, C., Van Trappen, P. O., Lemoine, N. R., and Hart, I. R. (2003) Combination of microdissection and microarray analysis to identify gene expression changes between differentially located tumour cells in breast cancer. Oncogene 22: 3742-3748.
85.Coombes, M. M., Briggs, K. L., Bone, J. R., Clayman, G. L., El-Naggar, A. K., and Dent, S. Y. (2003) Resetting the histone code at CDKN2A in HNSCC by inhibition of DNA methylation. Oncogene 22: 8902-8911.
86.Weinberger, P. M., Yu, Z., Haffty, B. G., Kowalski, D., Harigopal, M., Sasaki, C., Rimm, D. L., and Psyrri, A. (2004) Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer. Clin Cancer Res 10: 5684-5691.
87.McDermott, K. M., Zhang, J., Holst, C. R., Kozakiewicz, B. K., Singla, V., and Tlsty, T. D. (2006) p16(INK4a) prevents centrosome dysfunction and genomic instability in primary cells. PLoS Biol 4: e51.
88.Richon, V. M., Sandhoff, T. W., Rifkind, R. A., and Marks, P. A. (2000) Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc Natl Acad Sci U S A 97: 10014-10019.
89.Yoshida, M., Horinouchi, S., and Beppu, T. (1995) Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays 17: 423-430.
90.Sambucetti, L. C., Fischer, D. D., Zabludoff, S., Kwon, P. O., Chamberlin, H., Trogani, N., Xu, H., and Cohen, D. (1999) Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem 274: 34940-34947.
91.Zhong, Q., Chen, Y., Jones, D., and Lee, W. H. (1998) Perturbation of TSG101 protein affects cell cycle progression. Cancer Res 58: 2699-2702.
92.Marks, P., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., and Kelly, W. K. (2001) Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1: 194-202.
93.Mei, S., Ho, A. D., and Mahlknecht, U. (2004) Role of histone deacetylase inhibitors in the treatment of cancer (Review). Int J Oncol 25: 1509-1519.
94.Robertson, K. D., Ait-Si-Ali, S., Yokochi, T., Wade, P. A., Jones, P. L., and Wolffe, A. P. (2000) DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet 25: 338-342.
95.Magnaghi-Jaulin, L., Groisman, R., Naguibneva, I., Robin, P., Lorain, S., Le Villain, J. P., Troalen, F., Trouche, D., and Harel-Bellan, A. (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391: 601-605.
96.David, G., Neptune, M. A., and DePinho, R. A. (2002) SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological activities. J Biol Chem 277: 23658-23663.
97.Yang, S. H., and Sharrocks, A. D. (2004) SUMO promotes HDAC-mediated transcriptional repression. Mol Cell 13: 611-617.
98.Gill, G. (2004) SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18: 2046-2059.
99.Myers, E. L., and Allen, J. F. (2002) Tsg101, an inactive homologue of ubiquitin ligase e2, interacts specifically with human immunodeficiency virus type 2 gag polyprotein and results in increased levels of ubiquitinated gag. J Virol 76: 11226-11235.
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