進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-0812200910441852
論文名稱(中文) 探討三價砷對Trichostatin A所引起的EB病毒再活化的影響
論文名稱(英文) Inhibitory Effect of Arsenite on Trichostatin A-Induced Epstein-Barr Virus Reactivation
校院名稱 成功大學
系所名稱(中) 生物化學研究所
系所名稱(英) Department of Biochemistry
學年度 91
學期 2
出版年 92
研究生(中文) 許芸燕
研究生(英文) Yun-Yan Shu
學號 s1690403
學位類別 碩士
語文別 中文
論文頁數 98頁
口試委員 指導教授-吳華林
口試委員-施桂月
口試委員-江美治
口試委員-林淑華
中文關鍵字   再活化  起動子  病毒 
英文關鍵字 lytic cycle  arsenic  reactivation  promoter  Epstein-Barr virus 
學科別分類
中文摘要 EB病毒(Epstein-Barr virus)是人類gammaherpesvirus的一種,主要感染人體的表皮細胞和淋巴細胞,EB病毒感染和infectious mononucleosis、Burkitt’s lymphoma、鼻咽癌、Hodgkin’s lymphoma、posttransplant lymphoproliferative diseases等疾病有密切相關。在EB病毒感染B淋巴球後,病毒會保持在潛伏性感染的狀態。病毒的再活化可能會使病毒大量產生,導致急性的危害。目前已知當身體的免疫力較低弱時,例如:器官移植和骨髓移植的病人,有可能使病毒再活化。因此抑制病毒再活化,亦可能可以減輕疾病的惡化。

EB病毒可藉由基因的表現來調控病毒的潛伏及再活化,當病毒再活化時,病毒基因依其被轉錄的順序可分為三類:前早期(immediate-early)、早期(early)、晚期(late)基因。EB病毒由潛伏狀態進入再活化狀態時,需要前早期基因BZLF1和BRLF1的表現,BZLF1基因產物Zta蛋白是轉錄因子(transcription factor),可調控病毒早期基因,並啟動一連串基因的表現,使EB病毒再活化。已經有報告指出在in vitro的系統中,有一些物質,例如:trichostatin A(TSA)、12-O-tetradecanoylphorbol-13-acetate(TPA)、calcium ionophore、butyrate及anti-immunoglobulin抗體可以誘發潛伏性感染細胞的EB病毒再活化。

砷(As)是一種致癌性物質(carcinogen),長期飲用含砷飲水的居民可能導致烏腳病和許多癌症。然而,有研究發現,三氧化二砷(arsenic trioxide, As2O3)可以用來治療急性前骨髓性白血病(acute promyelocytic leukemia, APL)。本實驗主要研究,在EB病毒潛伏感染的細胞中,三價砷— NaAsO2對EB病毒潛伏及再活化的影響。以組織蛋白去乙醯酯酶(histone deacetylase)抑制劑trichostatin A(TSA)處理P3HR1細胞(EBV-positive Burkitt’s lymphoma細胞),會促使EB病毒再活化並且Zta、Rta及EA-D蛋白的表現增加,而NaAsO2同時存在下會抑制Zta、Rta及EA-D蛋白的表現,且隨NaAsO2濃度的增加,抑制作用越顯著。此結果顯示,NaAsO2具有抑制EB病毒再活化的能力。此外,北方墨點法顯示,NaAsO2會抑制TSA所誘發的BRLF1/BZLF1 mRNA及BZLF1 mRNA表現。已知TSA是一種組織蛋白去乙醯酯酶抑制劑,於是進一步探討NaAsO2是否直接影響TSA的作用,而產生抑制的效果。實驗結果顯示,NaAsO2不影響TSA所造成的histone hyperacetylation。

接著進一步研究NaAsO2對BZLF1起動子(promoter)的影響,發現NaAsO2可以抑制BZLF1起動子的活性。經由BZLF1起動子序列截短分析,找出TSA的反應區可能是在BZLF1起動子-236至-156之間。最後探討protein kinase C (PKC)、phosphatidylinositol 3-kinase (PI3-kinase)和p38 mitogen-activated protein kinase (p38 MAPK)的抑制劑對TSA與NaAsO2作用的影響。結果發現,PI3-kinase抑制劑和p38 MAPK抑制劑不會影響BZLF1起動子的基本活性,但PKC抑制劑會影響BZLF1起動子的基本活性,此外,PI3-kinase抑制劑和p38 MAPK抑制劑皆會抑制TSA活化BZLF1起動子。然而,這三種抑制劑皆不會影響到NaAsO2抑制BZLF1起動子的能力。實驗結果顯示,NaAsO2會抑制EB病毒BZLF1基因轉錄,進而抑制EB病毒再活化。
英文摘要 Epstein-Barr virus is a human gammaherpesvirus that infects epithelial and lymphoid cells. EBV is the causative agent of infectious mononucleosis and is assosiated with Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma and posttransplant lymphoproliferative diseases. EBV establishes a latent infection in B lymphocytes. However, EBV can be reactivated in immunocompromised hosts such as organ-transplanted and bone marrow-transplanted patients. EBV reactivation and replication might lead to spread of the virus through the body, thus, attenuation of EBV reactivation might assist in reducing the disease risk for EBV-associated malignancies.

It has been known that EBV reactivation from latency is initiated by the expression of the viral immediate-early genes, BZLF1 and BRLF1. The BZLF1 gene product Zta is a transcription factor which transactivates EBV immediate-early and early genes. Reactivation of EBV in latently infected cells can be induced by various agents, including trichostatin A (TSA), 12-O-tetradecanoylphorbol-13-acetate (TPA), calcium ionophore, butyrate and anti-immunoglobulin.

Although long term exposure of arsenic compounds (As) might cause skin and various cancers, arsenic trioxide (As2O3) has been used successfully in the treatment of acute promyelocytic leukemia (APL). In this study, we analyzed the effects of sodium arsenite (NaAsO2) on the EBV latency and reactivation. As shown in the previous report (Li-Kwan Chang and Shih-Tung Liu, 2000), TSA induced EBV reactivation in P3HR1 cells, allowing the virus to synthesize three viral lytic proteins—Zta, Rta and EA-D. We found that NaAsO2 inhibited the expression of the EBV lytic proteins in TSA-treated cells. Northern blot analysis also demonstrated the biosynthesis of the BRLF1/BZLF1 bicistronic mRNA and BZLF1 mRNA was inhibited by NaAsO2. On the other hand, treatment with NaAsO2 did not alter the level of acetylation of histones H3 and H4 induced by TSA.

Furthermore, the TSA-induced BZLF1 promoter activation was suppressed by NaAsO2. In promoter reporter gene assays, a series of deletion of the BZLF1 promoter (Zp) were constructed and tested for their response to TSA. The data showed that the region from -236 to -156 bp of Zp is important for conferring responsiveness to TSA. Moreover, site-directed mutagenesis analysis of the BZLF1 promoter revealed that ZIA, ZIB and ZII elements were involved in TSA responsiveness. Finally, we examined the effects of inhibitors of protein kinase C, phosphatidylinositol 3-kinase (PI3-K) and p38 mitogen-activated protein kinase (MAPK) on the BZLF1 promoter activity. In the TSA-untreated cells, the basal activity of the BZLF1 promoter was not affected by p38 MAPK and PI3-kinase inhibitors. In contrast, the basal activity of the BZLF1 promoter was affected by a protein kinase C inhibitor. TSA-mediated activation of the BZLF1 promoter could be blocked by the p38 MAPK and PI3-kinase inhibitor. However, these inhibitors did not affect the inhibitory effect of NaAsO2 on the BZLF1 promoter activity. These results suggested that NaAsO2 could inhibit TSA-induced EBV reactivation by inhibiting the transcription of the EBV immediate-early genes, BZLF1 and BRLF1.
論文目次 中文摘要-------------------------------------------------------------------------- 1
Abstract---------------------------------------------------------------------------- 3
誌謝-------------------------------------------------------------------------------- 5
目錄-------------------------------------------------------------------------------- 6
表、圖、附錄目錄-------------------------------------------------------------- 9
縮寫檢索表----------------------------------------------------------------------- 10
緒論-------------------------------------------------------------------------------- 12
藥品及材料----------------------------------------------------------------------- 17
儀器-------------------------------------------------------------------------------- 23
材料與方法----------------------------------------------------------------------- 26
一、P3HR1細胞的培養----------------------------------------------------- 26
A. P3HR1細胞之繼代培養------------------------------------------- 27
B. 冷凍保存細胞------------------------------------------------------- 27
C. 解凍細胞------------------------------------------------------------- 28
D. 細胞計數------------------------------------------------------------- 28
二、西方墨點法(Western blot)----------------------------------------- 28
A. 收取細胞溶解液---------------------------------------------------- 28
B. 酸萃取法收取細胞蛋白質(Acid extraction of proteins from cells)----------------------------------------------------------------- 30
C. 蛋白質濃度測定---------------------------------------------------- 31
D. 西方墨點法(Western blot)------------------------------------- 33
三、北方墨點法(Northern blot)---------------------------------------- 38
A. 萃取細胞全部的RNA--------------------------------------------- 38
B. RNA電泳------------------------------------------------------------- 40
C. 轉漬程序------------------------------------------------------------- 42
D. 探針(probe)之製備--------------------------------------------- 43
E. 雜交法(hybridization)------------------------------------------ 44
四、DNA基本技術操作與菌種保存------------------------------------- 46
A. 小量質體DNA抽取(mini-preparation of plasmid DNA) 46
B. 瓊脂膠電泳(agarose gel electrophoresis)-------------------- 47
C. 限制酶切割---------------------------------------------------------- 48
D. 以電泳法回收DNA(recovery of DNA fragment)--------- 49
E. 接合反應(ligation)---------------------------------------------- 52
F. E. coli competent cells (DH5α strain)之製備--------------------- 53
G. 形質轉移(transformation)-------------------------------------- 55
H. 核酸定序分析(DNA sequencing)----------------------------- 57
I. 長期菌種保存-------------------------------------------------------- 57
五、EB病毒BZLF1基因起動子(promoter)截短與突變的構築 57
A. EB病毒BZLF1基因起動子截短的構築:-156Zp和-132Zp的構築----------------------------------------------------------------- 57
B. EB病毒BZLF1基因起動子突變的構築:-236Zp(MZIA)、-236Zp(MZIB)和-236Zp(MZII)的構築---------------------------
60
C. 構築的質體DNA進行核酸定序--------------------------------- 63
六、BZLF1基因起動子(promoter)的活性分析--------------------- 64
A. P3HR1細胞的暫時性轉染(transient transfection)-電穿孔法(electroporation)-------------------------------------------
64
B. Luciferase報告基因的活性分析---------------------------------- 65
結果-------------------------------------------------------------------------------- 67
一、NaAsO2對EB病毒Zta、Rta及EA-D等蛋白質表現的影響-- 67
二、NaAsO2對EB病毒BZLF1 mRNA表現的影響------------------ 68
三、NaAsO2對EB病毒BZLF1起動子(promoter)的影響------------ 69
四、NaAsO2不影響TSA所造成的histone hyperacetylation--------- 69
五、尋找BZLF1起動子上TSA的response element------------------ 70
六、探討PKC、PI3-kinase和p38 MAPK的抑制劑對TSA與NaAsO2作用的影響----------------------------------------------------
71
討論-------------------------------------------------------------------------------- 72
參考文獻-------------------------------------------------------------------------- 76
表----------------------------------------------------------------------------------- 84
圖----------------------------------------------------------------------------------- 85
附錄-------------------------------------------------------------------------------- 95
自述-------------------------------------------------------------------------------- 98
參考文獻 Abernathy, C. O., Liu, Y.-P., Longfellow, D., Aposhian, H. V., Beck, B., Fowler, B., Goyer, R., Menzer, R., Rossman, T., Thompson, C. and Waalkes, M. Arsenic: health effects, mechanisms of actions, and research issues. Environ. Health Perspect. 107: 593-597 (1999).
Adamson, A. L., Darr, D., Holley-Guthrie, E., Johnson, R. A., Mauser, A., Swenson, J. and Kenney, S. Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun N-terminal kinases. J. Virol. 74: 1224-1233 (2000).
Andrews, J. M., Newbound, G. C., Oglesbee, M., Brady, J. N. and Lairmore, M. D. The cellular stress response enhances human T-cell lymphotropic virus type 1 basal gene expression through the core promoter region of the long terminal repeat. J. Virol. 71: 741-745 (1997).
Andrews, J. M., Oglesbee, M. J., Trevino, A. V., Guyot, D. J., Newbound, G. C. and Lairmore, M. D. Enhanced human T-cell lymphotropic virus type I expression following induction of the cellular stress response. Virology 208: 816-820 (1995).
Biggin, M., Bodescot, M., Perricaudet, M. and Farrell, P. Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells. J. Virol. 61: 3120-3132 (1987).
Boom, R., Sol, C. J. A., Minnaar, R. P., Geelen, J. L. M. C., Raap, A. K., Van Der Noordaa, J. Induction of gene expression under human cytomegalovirus immediate early enhancer-promoter control by inhibition of protein synthesis is cell cycle-dependent. J. Gen. Virol. 69: 1179-1193 (1988).
Burkitt, D. A children's cancer dependent on climatic factors. Nature 194: 232-234 (1962).
Chang, L.-K. and Liu, S.-T. Activation of the BRLF1 promoter and lytic cycle of Epstein-Barr virus by histone acetylation. Nucleic Acids Res. 28: 3918-3925 (2000).
Chang, Y.-N., Dong, D. L.-Y., Hayward, G. S. and Hayward, S. D. The Epstein-Barr virus Za transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif. J. Virol. 64: 3358-3369 (1990).
Chen, G.-Q., Shi, X.-G., Tang, W., Xiong, S.-M., Zhu, J., Cai, X., Han, Z.-G., Ni, J.-H., Shi, G.-Y., Jia, P.-M., Liu, M.-M., He, K.-L., Niu, C., Ma, J., Zhang, P., Zhang, T.-D., Paul, P., Naoe, T., Kitamura, K., Miller, W., Waxman, S., Wang, Z.-Y., de The, H., Chen, S.-J. and Chen, Z. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood 89: 3345-3353 (1997).
Chen, G.-Q., Zhu, J., Shi, X.-G., Ni, J.-H., Zhong, H.-J., Si, G.-Y., Jin, X.-L., Tang, W., Li, X.-S., Xong, S.-M., Shen, Z.-X., Sun, G.-L., Ma, J., Zhang, P., Zhang, T.-D., Gazin, C., Naoe, T., Chen, S.-J., Wang, Z.-Y. and Chen, Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bc1-2 expression and modulation of PML-RARα/PML proteins. Blood 88: 1052-1061 (1996).
Chen, H., Liu, J., Merrick, B. A. and Waalkes, M. P. Genetic events associated with arsenic-induced malignant transformation: applications of cDNA microarray technology. Mol. Carcinog. 30: 79-87 (2001).
Chevallier-Greco, A., Manet, E., Chavrier, P., Mosnier, C., Buillie, J. and Sergeant, A. Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO J. 5: 3243-3249 (1986).
Chiang, H. S., Guo, H. R., Hong, C. L., Lin, S. M. and Lee, E. F. The incidence of bladder cancer in the black foot disease endemic area in Taiwan. Br. J. Urol. 71: 274-278 (1993).
Chiou, H.-Y., Hsueh, Y.-M., Liaw, K.-F., Horng, S.-F., Chiang, M.-H., Pu, Y.-S., Lin, J. S.-N., Huang, C.-H. and Chen, C.-J. Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow-up study in Taiwan. Cancer Res. 55: 1296-1300 (1995).
Choi, H. S., Lee, J. H., Park, J. G. and Lee, Y. I. Trichostatin A, a histone deacetylase inhibitor, activates the IGFBP-3 promoter by upregulating Sp1 activity in hepatoma cells: alteration of the Sp1/Sp3/HDAC1 multiprotein complex. Biochem. Biophys. Res. Commun. 296: 1005-1012 (2002).
Chou, W.-C., Hawkins, A. L., Barrett, J. F., Griffin, C. A. and Dang, C. V. Arsenic inhibition of telomerase transcription leads to genetic instability. J. Clin. Invest. 108: 1541-1547 (2001).
Daibata, M., Speck, S. H., Mulder, C. and Sairenji, T. Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells. Virology 198: 446-454 (1994).
Darr, C. D., Mauser, A. and Kenney, S. Epstein-Barr virus immediate-early protein BRLF1 induces the lytic form of viral replication through a mechanism involving phosphatidylinositol-3 kinase activation. J. Virol. 75: 6135-6142 (2001).
Eickhoff, B., Germeroth, L., Stahl, C., Köhler, G., Rüller, S., Schlaak, M. and van der Bosch, J. Trichostatin A-mediated regulation of gene expression and protein kinase activities: reprogramming tumor cells for ribotoxic stress-induced apoptosis. Biol. Chem. 381: 1127-1132 (2000).
El-Sabban, M. E., Nasr, R., Dbaibo, G., Hermine, O., Abboushi, N., Quignon, F., Ameisen, J. C., Bex, F., de Thé, H. and Bazarbachi, A. Arsenic-interferon-α—triggered apoptosis in HTLV-I transformed cells is associated with tax down-regulation and reversal of NF-κB activation. Blood 96: 2849-2855 (2000).
Faggioni, A., Zompetta, C., Grimaldi, S., Barile, G., Frati, L. and Lazdins, J. Calcium modulation activates Epstein-Barr virus genome in latently infected cells. Science 232: 1554-1556 (1986).
Fahmi, H., Cochet, C., Hmama, Z., Opolon, P. and Joab, I. Transforming growth factor beta 1 stimulates expression of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA by an indirect mechanism which requires the MAPK kinase pathway. J. Virol. 74: 5810-5818 (2000).
Farrell, P. J., Rowe, D. T., Rooney, C. M. and Kouzarides, T. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO J. 8: 127-132 (1989).
Fixman, E. D., Hayward, G. S. and Hayward, S. D. Replication of Epstein-Barr virus oriLyt: lack of a dedicated virally encoded origin-binding protein and dependence on Zta in cotransfection assays. J. Virol. 69: 2998-3006 (1995).
Flemington, E. and Speck, S. H. Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1. J. Virol. 64: 1227-1232 (1990)a.
Flemington, E. and Speck, S. H. Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1. J. Virol. 64: 1217-1226 (1990)b.
Flemington, E. K., Goldfeld, A. E. and Speck, S. H. Efficient transcription of the Epstein-Barr virus immediate-early BZLF1 and BRLF1 genes requires protein synthesis. J. Virol. 65: 7073-7077 (1991).
Fukuda, M., Ikuta, K., Yanagihara, K., Tajima, M., Kuratsune, H., Kurata, T. and Sairenji, T. Effect of transforming growth factor-β1 on the cell growth and Epstein-Barr virus reactivation in EBV-infected epithelial cell lines. Virology 288: 109-118 (2001).
Gao, X., Ikuta, K., Tajima, M. and Sairenji, T. 12-O-tetradecanoylphorbol-13-acetate induces Epstein-Barr virus reactivation via NF-κB and AP-1 as regulated by protein kinase C and mitogen-activated protein kinase. Virology 286: 91-99 (2001).
Geelen, J. L. M. C., Boom, R., Klaver, G. P. M., Minnaar, R. P., Feltkamp, M. C. W., Van Milligen, F. J., Sol, C. J. A. and Van Der Noordaa, J. Transcriptional activation of the major immediate early transcription unit of human cytomegalovirus by heat-shock, arsenic and protein synthesis inhibitors. J. Gen. Virol. 68: 2925-2931 (1987).
Gustafsson, A., Levitsky, V., Zou, J.-Z., Frisan, T., Dalianis, T., Ljungman, P., Ringden, O., Winiarski, J., Emberg, I. and Masucci, M. G. Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Blood 95: 807-814 (2000).
Hanto, D. W., Frizzera, G., Gajl-Peczalska, K. J. and Simmons, R. L. Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation 39: 461-472 (1985).
Heydorn, K. Environmental variation of arsenic levels in human blood determines by neutron activation analysis. Clin. Chim. Acta. 28: 349-357 (1970).
Holley-Guthrie, E. A., Quinlivan, E. B., Mar, E.-C. and Kenney, S. The Epstein-Barr virus (EBV) BMRF1 promoter for early antigen (EA-D) is regulated by the EBV transactivators, BRLF1 and BZLF1, in a cell-specific manner. J. Virol. 64: 3753-3759 (1990).
Hu, Y., Jin, X. and Snow, E. T. Effect of arsenic on transcription factor AP-1 and NF-κB DNA binding activity and related gene expression. Toxicol. Lett. 133: 33-45 (2002).
Hughes, M. F. Arsenic toxicity and potential mechanisms of action. Toxicol. Lett. 133: 1-16 (2002).
Jenkins, P. J., Binne, U. K. and Farrell, P. J. Histone acetylation and reactivation of Epstein-Barr virus from latency. J. Virol. 74: 710-720 (2000).
Kapahi, P., Takahashi, T., Natoli, G., Adams, S. R., Chen, Y., Tsien, R. Y. and Karin, M. Inhibition of NF-κB activation by arsenite through reaction with a critical cysteine in the activation loop of IκB kinase. J. Biol. Chem. 275: 36062-36066 (2000).
Kenagy, D. N., Schlesinger, Y., Weck, K., Ritter, J. H., Gaudreault-Keener, M. M. and Storch, G. A. Epstein-Barr virus DNA in peripheral blood leukocytes of patients with posttransplant lymphoproliferative disease. Transplantation 60: 547-554 (1995).
Kenney, S., Kamine, J., Holley-Guthrie, E., Lin, J.-C., Mar, E.-C. and Pagano, J. The Epstein-Barr virus (EBV) BZLF1 immediate-early gene product differentially affects latent versus productive EBV promoters. J. Virol. 63: 1729-1736 (1989).
Kitchin, K. T. Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol. Appl. Pharmacol. 172: 249-261 (2001).
Lee, T.-C., Oshimura, M. and Barrett, J. C. Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture. Carcinogenesis 6: 1421-1426 (1985).
Lieberman, P. M. and Berk, A. J. In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein-Barr virus Zta protein. J. Virol. 64: 2560-2568 (1990).
Liu, P., Liu, S. and Speck, S. H. Identification of a negative cis element within the ZII domain of the Epstein-Barr virus lytic switch BZLF1 gene promoter. J. Virol. 72: 8230-8239 (1998).
Liu, S., Liu, P., Borras, A., Chatila, T. and Speck, S. H. Cyclosporin A-sensitive induction of the Epstein-Barr virus lytic switch is mediated via a novel pathway involving a MEF2 family member. EMBO J. 16: 143-153 (1997)a.
Liu, S., Borras, A. M., Liu, P., Suske, G. and Speck, S. H. Binding of the ubiquitous cellular transcription factors Sp1 and Sp3 to the ZI domains in the Epstein-Barr virus lytic switch BZLF1 gene promoter. Virology 228: 11-18 (1997)b.
Lucas, K. G., Burton, R. L., Zimmerman, S. E., Wang, J., Cornetta, K. G., Robertson, K. A., Lee, C. H. and Emanuel, D. J. Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the determination of patients at risk for EBV-induced lymphoproliferative disease after stem cell transplantation. Blood 91: 3654-3661 (1998).
Luka, J., Kallin, B. and Klein, G. Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate. Virology 94: 228-231 (1979).
Manet, E., Gruffat, H., Trescol-Biemont, M. C., Moreno, N., Chambard, P., Giot, J. F. and Sergeant, A. Epstein-Barr virus bicistronic mRNAs generated by facultative splicing code for two transcriptional transactivators. EMBO J. 8: 1819-1826 (1989).
Mauser, A., Holley-Guthrie, E., Simpson, D., Kaufmann, W. and Kenney, S. The Epstein-Barr virus immediate-early protein BZLF1 induces both a G2 and a mitotic block. J. Virol. 76: 10030-10037 (2002).
Niu, C., Yan, H., Yu, T., Sun, H.-P., Liu, J.-X., Li, X.-S., Wu, W., Zhang, F.-Q., Chen, Y., Zhou, L., Li, J.-M., Zeng, X.-Y., Yang, R.-R. O., Yuan, M.-M., Ren, M.-Y., Gu, F.-Y., Cao, Q., Gu, B.-W., Su, X.-Y., Chen, G.-Q., Xiong, S.-M., Zhang, T.-D., Waxman, S., Wang, Z.-Y., Chen, Z., Hu, J., Shen, Z.-X. and Chen, S.-J. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 94: 3315-3324 (1999).
Patel, J., McLeod, L. E., Vries, R. G. J., Flynn, A., Wang, X. and Proud, C. G. Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors. Eur. J. Biochem. 269: 3076-3085 (2002).
Perkins, C., Kim, C. N., Fang, G. and Bhalla, K. N. Arsenic induces apoptosis of multidrug-resistant human myeloid leukemia cells that express Bcr-Abl or overexpress MDR, MRP, Bcl-2, or Bcl-xL. Blood 95: 1014-1022 (2000).
Roboz, G. J., Dias, S., Lam, G., Lane, W. J., Soignet, S. L., Jr, R. P. W. and Rafii, S. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96: 1525-1530 (2000).
Roizman, B., Whitley, R. J. and Lopez, C. The human herpesviruses. Raven Press. New York. pp. 107-172 (1993).
Rooney, C. M., Rowe, D. T., Ragot, T. and Farrell, P. J. The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. J. Virol. 63: 3109-3116 (1989).
Roussel, R. R. and Barchowsky, A. Arsenic inhibits NF-κB-mediated gene transcription by blocking IκB kinase activity and IκBα phosphorylation and degradation. Arch. Biochem. Biophys. 377: 204-212 (2000).
Schepers, A., Pich, D. and Hammerschmidt, W. A transcription factor with homology to the AP-1 family links RNA transcription and DNA replication in the lytic cycle of Epstein-Barr virus. EMBO J. 12: 3921-3929 (1993).
Shen, Z.-X., Chen, G.-Q., Ni, J.-H., Li, X.-S., Xiong, S.-M., Qiu, Q.-Y., Zhu, J., Tang, W., Sun, G.-L., Yang, K.-Q., Chen, Y., Zhou, L., Fang, Z.-W., Wang, Y.-T., Ma, J., Zhang, P., Zhang, T.-D., Chen, S.-J., Chen, Z. and Wang, Z.-Y. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. clinical efficacy and pharmacokinetics in relapsed patients. Blood 89: 3354-3360 (1997).
Shimizu, N. and Takada, K. Analysis of the BZLF1 promoter of Epstein-Barr virus: identification of an anti-immunoglobulin response sequence. J. Virol. 67: 3240-3245 (1993).
Sinclair, A. J., Brimmell, M., Shanahan, F. and Farrell, P. J. Pathways of activation of the Epstein-Barr virus productive cycle. J. Virol. 65: 2237-2244 (1991).
Smith, A. H., Goycolea, M., Haque, R. and Biggs, M. L. Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water. Am. J. Epidemiol. 147: 660-669 (1998).
Sommers, S. C. and McManus, R. G. Multiple arsenical cancers of skin and internal organs. Cancer 6: 347-359 (1953).
Speck, S. H., Chatila, T. and Flemington, E. Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol. 5: 399-405 (1997).
Stevens, S. J. C., Verschuuren, E. A. M., Pronk, I., van der Bij, W., Harmsen, M. C., The, T. H., Meijer, C. J. L. M., van der Brule, A. J. C. and Middeldorp, J. M. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood 97: 1165-1171 (2001).
Takada, K. and Ono, Y. Synchronous and sequential activation of latently infected Epstein-Barr virus genomes. J. Virol. 63: 445-449 (1989).
Takahashi, M., Barrett, J. C. and Tsutsui, T. Transformation by inorganic arsenic compounds of normal Syrian hamster embryo cells into a neoplastic state in which they become anchorage-independent and cause tumors in newborn hamsters. Int. J. Cancer 99: 629-634 (2002).
Tseng, C.-H., Chong, C.-K., Chen, C.-J. and Tai, T.-Y. Dose-response relationship between peripheral vascular disease and ingested inorganic arsenic among residents in blackfoot disease endemic villages in Taiwan. Atherosclerosis 120: 125-133 (1996).
Tsuda, T., Babazono, A., Yamamoto, E., Kurumatani, N., Mino, Y., Ogawa, T., Kishi, Y. and Aoyama, H. Ingested arsenic and internal cancer: a historical cohort study followed for 33 years. Am. J. Epidemiol. 141: 198-209 (1995).
Um, S.-J., Lee, S.-Y., Kim, E.-J., Myoung, J., Namkoong, S.-E. and Park, J.-S. Down-regulation of human papillomavirus E6/E7 oncogene by arsenic trioxide in cervical carcinoma cells. Cancer Lett. 181: 11-22 (2002).
Urier, G., Buisson, M., Chambard, P. and Sergeant, A. The Epstein-Barr virus early protein EB1 activates transcription from different responsive elements including AP-1 binding sites. EMBO J. 8: 1447-1453 (1989).
Van Esser, J. W. J., van der Holt, B., Meijer, E., Niesters, H. G. M., Trenschel, R., Thijsen, S. F. T., van Loon, A. M., Frassoni, F., Bacigalupo, A., Schaefer, U. W., Osterhaus, A. D. M. E., Gratama, J. W., Löwenberg, B., Verdonck, L. F. and Cornelissen, J. J. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell—depleted SCT. Blood 98: 972-978 (2001).
Vasconcelos, D., Norrby, E. and Oglesbee, M. The cellular stress response increases measles virus-induced cytopathic effect. J. Gen. Virol. 79: 1769-1773 (1998).
Wang, Y.-C. J., Huang, J.-M. and Montalvo, E. A. Characterization of proteins binding to the ZII element in the Epstein-Barr virus BZLF1 promoter: transactivation by ATF1. Virology 227: 323-330 (1997).
Wang, Z.-G., Rivi, R., Delva, L., König, A., Scheinberg, D. A., Gambacorti-Passerini, C., Gabrilove, J. L., Jr, R. P. W. and Pandolfi, P. P. Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARα independent manner. Blood 92: 1497-1504 (1998).
Yoshida, M., Kijima, M., Akita, M. and Beppu, T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J. Biol. Chem. 265: 17174-17179 (1990)a.
Yoshida, M., Hoshikawa, Y., Koseki, K., Mori, K. and Beppu, T. Structural specificity for biological activity of trichostatin A, a specific inhibitor of mammalian cell cycle with potent differentiation-inducing activity in friend leukemia cells. J. Antibiotics XLIII: 1101-1106 (1990)b.
Zalani, S., Holley-Guthrie, E. A., Gutsch, D. E. and Kenney, S. C. The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor. J. Virol. 66: 7282-7292 (1992).
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2097-08-14起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2097-08-14起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw