跳到主要內容

臺灣博碩士論文加值系統

(18.97.14.86) 您好!臺灣時間:2025/02/09 02:13
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:鄭瑋婷
研究生(外文):Wei-Ting Cheng
論文名稱:Bcl-xL去醯胺基化與癌細胞對Cisplatin的敏感性呈正相關
論文名稱(外文):Bcl-xL Deamidation of Cancer Cells Correlates with Cisplatin-induced Cytotoxicity
指導教授:陳一村
指導教授(外文):I-Tsuen Chen
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:73
中文關鍵詞:去醯胺基化cisplatinBcl-xL
外文關鍵詞:deamidationcisplatinBcl-xL
相關次數:
  • 被引用被引用:0
  • 點閱點閱:179
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
近年來有研究指出,DNA損傷抗癌藥物可引起癌症細胞之Bcl-xL去醯胺基化,去醯胺基化後的Bcl-xL會失去抗凋亡活性,導致細胞凋亡;另人驚訝的是,這樣的現象會受到Rb的表現而抑制。在我們之前的研究中也發現,E1A可經由與Rb作用使卵巢癌細胞 (SKOV3.ip1) 對cisplatin敏感並引起Bcl-xL去醯胺基化。此外,證實了送入去醯胺基化的Bcl-xL (N52/66D) 到卵巢癌細胞中會促進細胞凋亡;而無法去醯胺基化的Bcl-xL (N52/66A) 則可保護細胞抵抗E1A引起的cisplatin敏感化。延續上述的實驗,在此我們觀察到去醯胺基化作用並不影響Bcl-xL與Bad之間的結合關係,而且外送p53至SKOV3.ip1細胞中,對cisplatin引起的細胞死亡和Bcl-xL去醯胺基化程度並無明顯影響。接著我們觀察四種Rb和p53基因表現狀態不同的癌細胞株,發現cisplatin引起之Bcl-xL去醯胺基化與細胞對cisplatin敏感程度密切相關,而且表現E1A並無法促使對cisplatin有抗藥性細胞 (wild-typed Rb) 之Bcl-xL去醯胺基化。在體外鹼性pH實驗中發現所有細胞都可被引起高比率的Bcl-xL去醯胺基化,由此推論,上述對cisplatin有抗藥性的細胞中無法引起Bcl-xL去醯胺基化的原因並非由於胺基酸52和66位置上發生突變所致。此外,Bcl-2的表現量在對cisplatin敏感與有抗藥性的細胞中有很大的差異,Bcl-2表達高則細胞抗藥性也高。最後,我們發現抗氧化劑N-acetylcysteine (NAC) 可阻斷cisplatin引起之Bcl-xL去醯胺基化和細胞凋亡,推測cisplatin引起Bcl-xL去醯胺基化的機制可能與ROS亦有關。
Previous studies have shown that chemotherapy causes deamidation of the protein Bcl-xL in tumor cells. This Bcl-xL deamidation inhibits its antiapoptotic ability and sensitizes tumor cells to cisplatin treatment. Surprisingly, Rb inhibits this process. To test this model, we have shown recently that E1A-mediated Rb inactivation in an ovarian cancer cell line (SKOV3.ip1) leads to Bcl-xL deamidation which contributes to cisplatin-induced apoptosis. Furthermore, ectopic expression of deamidated form of Bcl-xL (N52/66D) enhances cell death, whereas the nondeamidated Bcl-xL (N52/66A) protects E1A-mediated apoptosis. In this follow-up studies, we showed that BH3 protein bad interacts equally well with all three forms of Bcl-xL protein. In addition, ectopic expression of p53 did not enhance cell death or Bcl-xL deamidation in SKOV3.ip1. To test whether Bcl-xL deamidation occurs in other cancer cells, we selected four cancer cell lines with various Rb and p53 status. Our data show that the cell lines sensitive to cisplatin correlated with induction of Bcl-xL deamidation, whereas the cell lines resistant to cisplatin exhibited no induction of Bcl-xL deamidation. Interestingly, expression of E1A did not sensitize the cisplatin-resistant cell lines or Bcl-xL deamidation. Both the cisplatin-resistant cell lines are Rb wt. Furthermore, In vitro alkaline treatment induced Bcl-xL deamidation in these cell lines, suggesting that no induction of Bcl-xL deamidation in the cisplatin- resistant cell lines is not due to mutation of Bcl-xL at 55 and 66 residues. We also noticed that level of Bcl-2 was higher in the cisplatin-resistant cells than in the cisplatin-sensitive cells. Moreover, we found that N-acetylcysteine protected cells from cisplatin induced apoptosis and repressed Bcl-xL deamidation. This suggested that reactive oxygen species (ROS) may be involved in the induction of Bcl-xL deamidation by cisplatin.
目錄
摘要 3
Abstract 4
壹、緒論 6
順-雙胺雙氯鉑 (cisplatin) 6
E1A (Human adenovirus-5 early gene 1A) 7
Rb and E2F 9
Bcl-xL and Bad 11
Protein deamidation 12
Bcl-xL deamidation 13
貳、材料與實驗方法 16
一、材料 16
(一)細胞株: 16
(二)細胞培養材料: 16
(三)藥品: 17
(四)質體(plasmids): 17
(五)Markers: 17
(六)Membrane and Filter Paper: 18
(七)Kit, Reagents and Chemicals: 18
(八)抗體: 19
二、實驗方法 19
(一)細胞培養與操作 19
(二)轉型作用(Transformation) 21
(三)質體DNA製備(Plasmid DNA midi preparation) 21
(四)暫時性轉殖(Transient transfectoin) 22
(五)免疫沉澱(Immunoprecipitation) 23
(六)西方墨點法(Western blot) 23
(七)細胞存活率分析(MTT assay) 26
(九)Phosphatase的處理 27
(十)Bcl-xL deamidation ratio的計算法 27
參、實驗結果 28
一、Bcl-xL去醯胺基化後仍與凋亡蛋白Bad結合 28
二、異位性表現p53並不造成卵巢癌細胞 (p53-null;wild-type Rb) 的死亡。 29
三、異位性表現p53會選擇性抑制癌症細胞的增殖 29
四、異位性表現p53不影響cisplatin引起卵巢癌細胞之Bcl-xL去醯胺基化 30
五、在不同的癌細胞株中cisplatin引發不同程度的細胞死亡 31
六、Bcl-xL去醯胺基化與否與細胞對cisplatin的敏感度有關 32
七、 H1299和BT474細胞株中,暫時轉殖表現E1A無法促使cispaltin引起Bcl-xL去醯胺基化 32
八、在鹼性環境中Bcl-xL去醯胺基化明顯增加 33
九、Cisplatin引起之Bcl-xL修飾並非磷酸化作用(phosphorylation) 34
十、H1299和BT474兩株細胞具有高表達的Bcl-2蛋白 35
十二、N-Acetylcysteine保護細胞免於受到cisplatin傷害而凋亡 35
肆、實驗討論 37
伍、參考文獻 43
陸、圖表 54
附錄一 65
附錄二 67
附錄三 73
參考文獻
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.
Antonsson, B. (2001). Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion. Cell Tissue Res 306, 347-361.
Aritomi, M., Kunishima, N., Inohara, N., Ishibashi, Y., Ohta, S., and Morikawa, K. (1997). Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family. J Biol Chem 272, 27886-27892.
Baker, S. J., Markowitz, S., Fearon, E. R., Willson, J. K., and Vogelstein, B. (1990). Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249, 912-915.
Baptiste, N., and Prives, C. (2004). p53 in the cytoplasm: a question of overkill? Cell 116, 487-489.
Benhar, M., Dalyot, I., Engelberg, D., and Levitzki, A. (2001). Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress. Mol Cell Biol 21, 6913-6926.
Bosco, G., Du, W., and Orr-Weaver, T. L. (2001). DNA replication control through interaction of E2F-RB and the origin recognition complex. Nat Cell Biol 3, 289-295.
Chaney, S. G., and Vaisman, A. (1999). Specificity of platinum-DNA adduct repair. J Inorg Biochem 77, 71-81.
Chang, C. Y., Lin, Y. M., Lee, W. P., Hsu, H. H., and Chen, E. I. (2006). Involvement of Bcl-X(L) deamidation in E1A-mediated cisplatin sensitization of ovarian cancer cells. Oncogene 25, 2656-2665.
Chattopadhyay, D., Ghosh, M. K., Mal, A., and Harter, M. L. (2001). Inactivation of p21 by E1A leads to the induction of apoptosis in DNA-damaged cells. J Virol 75, 9844-9856.
Chau, B. N., and Wang, J. Y. (2003). Coordinated regulation of life and death by RB. Nat Rev Cancer 3, 130-138.
Chipuk, J. E., Maurer, U., Green, D. R., and Schuler, M. (2003). Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell 4, 371-381.
Classon, M., and Dyson, N. (2001). p107 and p130: versatile proteins with interesting pockets. Exp Cell Res 264, 135-147.
Datta, S. R., Brunet, A., and Greenberg, M. E. (1999). Cellular survival: a play in three Akts. Genes Dev 13, 2905-2927.
Davis, P. L., Shaiu, W. L., Scott, G. L., Iglehart, J. D., Hsieh, T. S., and Marks, J. R. (1998). Complex response of breast epithelial cell lines to topoisomerase inhibitors. Anticancer Res 18, 2919-2932.
Deverman, B. E., Cook, B. L., Manson, S. R., Niederhoff, R. A., Langer, E. M., Rosova, I., Kulans, L. A., Fu, X., Weinberg, J. S., Heinecke, J. W., et al. (2002). Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage. Cell 111, 51-62.
Donahue, B. A., Augot, M., Bellon, S. F., Treiber, D. K., Toney, J. H., Lippard, S. J., and Essigmann, J. M. (1990). Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin. Biochemistry 29, 5872-5880.
Downward, J. (1999). How BAD phosphorylation is good for survival. Nat Cell Biol 1, E33-35.
Dyson, N. (1998). The regulation of E2F by pRB-family proteins. Genes Dev 12, 2245-2262.
Egan, C., Bayley, S. T., and Branton, P. E. (1989). Binding of the Rb1 protein to E1A products is required for adenovirus transformation. Oncogene 4, 383-388.
el-Khateeb, M., Appleton, T. G., Gahan, L. R., Charles, B. G., Berners-Price, S. J., and Bolton, A. M. (1999). Reactions of cisplatin hydrolytes with methionine, cysteine, and plasma ultrafiltrate studied by a combination of HPLC and NMR techniques. J Inorg Biochem 77, 13-21.
Fattaey, A. R., Harlow, E., and Helin, K. (1993). Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes. Mol Cell Biol 13, 7267-7277.
Fink, D., Aebi, S., and Howell, S. B. (1998). The role of DNA mismatch repair in drug resistance. Clin Cancer Res 4, 1-6.
Flatmark, T., and Sletten, K. (1968). Multiple forms of cytochrome c in the rat. Precursor-product relationship between the main component Cy I and the minor components Cy II and Cy 3 in vivo. J Biol Chem 243, 1623-1629.
Flint, J., and Shenk, T. (1989). Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet 23, 141-161.
Friend, S. H., Bernards, R., Rogelj, S., Weinberg, R. A., Rapaport, J. M., Albert, D. M., and Dryja, T. P. (1986). A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643-646.
Frisch, S. M. (1991). Antioncogenic effect of adenovirus E1A in human tumor cells. Proc Natl Acad Sci U S A 88, 9077-9081.
Frisch, S. M., and Mymryk, J. S. (2002). Adenovirus-5 E1A: paradox and paradigm. Nat Rev Mol Cell Biol 3, 441-452.
Giaccone, G. (2000). Clinical perspectives on platinum resistance. Drugs 59 Suppl 4, 9-17; discussion 37-18.
Graham, F. L., van der Eb, A. J., and Heijneker, H. L. (1974). Size and location of the transforming region in human adenovirus type 5 DNA. Nature 251, 687-691.
Gross, A., McDonnell, J. M., and Korsmeyer, S. J. (1999). BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13, 1899-1911.
Harbour, J. W., and Dean, D. C. (2000). Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2, E65-67.
Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K., and Elledge, S. J. (1993). The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75, 805-816.
Harper, J. W., Elledge, S. J., Keyomarsi, K., Dynlacht, B., Tsai, L. H., Zhang, P., Dobrowolski, S., Bai, C., Connell-Crowley, L., Swindell, E., and et al. (1995). Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell 6, 387-400.
Hengartner, M. O. (2000). The biochemistry of apoptosis. Nature 407, 770-776.
Herrlich, P., and Bohmer, F. D. (2000). Redox regulation of signal transduction in mammalian cells. Biochem Pharmacol 59, 35-41.
Houweling, A., van den Elsen, P. J., and van der Eb, A. J. (1980). Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA. Virology 105, 537-550.
Howe, J. A., Mymryk, J. S., Egan, C., Branton, P. E., and Bayley, S. T. (1990). Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis. Proc Natl Acad Sci U S A 87, 5883-5887.
Huang, D. C., and Strasser, A. (2000). BH3-Only proteins-essential initiators of apoptotic cell death. Cell 103, 839-842.
Huang, Z. (2000). Bcl-2 family proteins as targets for anticancer drug design. Oncogene 19, 6627-6631.
Hubberstey, A. V., Pavliv, M., and Parks, R. J. (2002). Cancer therapy utilizing an adenoviral vector expressing only E1A. Cancer Gene Ther 9, 321-329.
Jacobson, M. D. (1996). Reactive oxygen species and programmed cell death. Trends Biochem Sci 21, 83-86.
Johnson, B. A., Shirokawa, J. M., and Aswad, D. W. (1989). Deamidation of calmodulin at neutral and alkaline pH: quantitative relationships between ammonia loss and the susceptibility of calmodulin to modification by protein carboxyl methyltransferase. Arch Biochem Biophys 268, 276-286.
Kelekar, A., and Thompson, C. B. (1998). Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8, 324-330.
Kelland, L. R. (1993). New platinum antitumor complexes. Crit Rev Oncol Hematol 15, 191-219.
Kelland, L. R. (2000). Preclinical perspectives on platinum resistance. Drugs 59 Suppl 4, 1-8; discussion 37-38.
Kern, S. E., Pietenpol, J. A., Thiagalingam, S., Seymour, A., Kinzler, K. W., and Vogelstein, B. (1992). Oncogenic forms of p53 inhibit p53-regulated gene expression. Science 256, 827-830.
Kharbanda, S., Pandey, P., Schofield, L., Israels, S., Roncinske, R., Yoshida, K., Bharti, A., Yuan, Z. M., Saxena, S., Weichselbaum, R., et al. (1997). Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis. Proc Natl Acad Sci U S A 94, 6939-6942.
Langerak A.D., Dreisbach L.P. (2001) Chemotherapy regimens and cancer care. Landes Bioscience, Georgetown, Texas.
Lee, W. H., Bookstein, R., Hong, F., Young, L. J., Shew, J. Y., and Lee, E. Y. (1987). Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235, 1394-1399.
Levine, A. J. (1997). p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.
Li, C., and Thompson, C. B. (2002). Cancer. DNA damage, deamidation, and death. Science 298, 1346-1347.
Lindner, H., and Helliger, W. (2001). Age-dependent deamidation of asparagine residues in proteins. Exp Gerontol 36, 1551-1563.
Lipinski, M. M., and Jacks, T. (1999). The retinoblastoma gene family in differentiation and development. Oncogene 18, 7873-7882.
Masuda, H., Tanaka, T., and Takahama, U. (1994). Cisplatin generates superoxide anion by interaction with DNA in a cell-free system. Biochem Biophys Res Commun 203, 1175-1180.
Meier, P., Finch, A., and Evan, G. (2000). Apoptosis in development. Nature 407, 796-801.
Minn, A. J., Velez, P., Schendel, S. L., Liang, H., Muchmore, S. W., Fesik, S. W., Fill, M., and Thompson, C. B. (1997). Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature 385, 353-357.
Mittnacht, S., Lees, J. A., Desai, D., Harlow, E., Morgan, D. O., and Weinberg, R. A. (1994). Distinct sub-populations of the retinoblastoma protein show a distinct pattern of phosphorylation. Embo J 13, 118-127.
Morgenbesser, S. D., Williams, B. O., Jacks, T., and DePinho, R. A. (1994). p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 371, 72-74.
Muchmore, S. W., Sattler, M., Liang, H., Meadows, R. P., Harlan, J. E., Yoon, H. S., Nettesheim, D., Chang, B. S., Thompson, C. B., Wong, S. L., et al. (1996). X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 381, 335-341.
Muller, P., Ceskova, P., and Vojtesek, B. (2005). Hsp90 is essential for restoring cellular functions of temperature-sensitive p53 mutant protein but not for stabilization and activation of wild-type p53: implications for cancer therapy. J Biol Chem 280, 6682-6691.
Mulligan, G., and Jacks, T. (1998). The retinoblastoma gene family: cousins with overlapping interests. Trends Genet 14, 223-229.
Mymryk, J. S., Shire, K., and Bayley, S. T. (1994). Induction of apoptosis by adenovirus type 5 E1A in rat cells requires a proliferation block. Oncogene 9, 1187-1193.
Nakajima, T., Morita, K., Ohi, N., Arai, T., Nozaki, N., Kikuchi, A., Osaka, F., Yamao, F., and Oda, K. (1996). Degradation of topoisomerase IIalpha during adenovirus E1A-induced apoptosis is mediated by the activation of the ubiquitin proteolysis system. J Biol Chem 271, 24842-24849.
Nemunaitis, J., and O'Brien, J. (2002). Head and neck cancer: gene therapy approaches. Part II: genes delivered. Expert Opin Biol Ther 2, 311-324.
Nevins, J. R. (1998). Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ 9, 585-593.
Nevins, J. R. (2001). The Rb/E2F pathway and cancer. Hum Mol Genet 10, 699-703.
Nielsen, S. J., Schneider, R., Bauer, U. M., Bannister, A. J., Morrison, A., O'Carroll, D., Firestein, R., Cleary, M., Jenuwein, T., Herrera, R. E., and Kouzarides, T. (2001). Rb targets histone H3 methylation and HP1 to promoters. Nature 412, 561-565.
Ohki, R., Nemoto, J., Murasawa, H., Oda, E., Inazawa, J., Tanaka, N., and Taniguchi, T. (2000). Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase. J Biol Chem 275, 22627-22630.
Ozols, R. F. (1991). Ovarian cancer: new clinical approaches. Cancer Treat Rev 18 Suppl A, 77-83.
Pickering, M. T., and Kowalik, T. F. (2006). Rb inactivation leads to E2F1-mediated DNA double-strand break accumulation. Oncogene 25, 746-755.
Pinto, A. L., and Lippard, S. J. (1985). Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta 780, 167-180.
Poirier, M. C., Reed, E., Ozols, R. F., Fasy, T., and Yuspa, S. H. (1987). DNA adducts of cisplatin in nucleated peripheral blood cells and tissues of cancer patients. Prog Exp Tumor Res 31, 104-113.
Poirier, M. C., Shamkhani, H., Reed, E., Tarone, R. E., and Gupta-Burt, S. (1992). DNA adducts induced by platinum drug chemotherapeutic agents in human tissues. Prog Clin Biol Res 374, 197-212.
Pomerantz, J., Schreiber-Agus, N., Liegeois, N. J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H. W., et al. (1998). The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92, 713-723.
Prabhu, S. D., Wang, G., Luo, J., Gu, Y., Ping, P., and Chandrasekar, B. (2003). Beta-adrenergic receptor blockade modulates Bcl-X(S) expression and reduces apoptosis in failing myocardium. J Mol Cell Cardiol 35, 483-493.
Robinson, A. B. (1974). Evolution and the distribution of glutaminyl and asparaginyl residues in proteins. Proc Natl Acad Sci U S A 71, 885-888.
Robinson, A. B., McKerrow, J. H., and Cary, P. (1970). Controlled deamidation of peptides and proteins: an experimental hazard and a possible biological timer. Proc Natl Acad Sci U S A 66, 753-757.
Robinson, A. B., McKerrow, J. H., and Legaz, M. (1974). Sequence dependent deamidation rates for model peptides of cytochrome C. Int J Pept Protein Res 6, 31-35.
Robinson, A. B., Scotchler, J. W., and McKerrow, J. H. (1973). Rates of nonenzymatic deamidation of glutaminyl and asparaginyl residues in pentapeptides. J Am Chem Soc 95, 8156-8159.
Robinson, N. E. (2002). Protein deamidation. Proc Natl Acad Sci U S A 99, 5283-5288.
Robinson, N. E., and Robinson, A. B. (2001). Deamidation of human proteins. Proc Natl Acad Sci U S A 98, 12409-12413.
Rowe, D. T., Graham, F. L., and Branton, P. E. (1983). Intracellular localization of adenovirus type 5 tumor antigens in productively infected cells. Virology 129, 456-468.
Royzman, I., Austin, R. J., Bosco, G., Bell, S. P., and Orr-Weaver, T. L. (1999). ORC localization in Drosophila follicle cells and the effects of mutations in dE2F and dDP. Genes Dev 13, 827-840.
Ruley, H. E. (1983). Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature 304, 602-606.
Samuelson, A. V., and Lowe, S. W. (1997). Selective induction of p53 and chemosensitivity in RB-deficient cells by E1A mutants unable to bind the RB-related proteins. Proc Natl Acad Sci U S A 94, 12094-12099.
Sanchez-Prieto, R., Quintanilla, M., Cano, A., Leonart, M. L., Martin, P., Anaya, A., and Ramon y Cajal, S. (1996). Carcinoma cell lines become sensitive to DNA-damaging agents by the expression of the adenovirus E1A gene. Oncogene 13, 1083-1092.
Schmitt, C. A., and Lowe, S. W. (1999). Apoptosis and therapy. J Pathol 187, 127-137.
Scotchler, J. W., and Robinson, A. B. (1974). Deamidation of glutaminyl residues: dependence on pH, temperature, and ionic strength. Anal Biochem 59, 319-322.
Shao, R., Karunagaran, D., Zhou, B. P., Li, K., Lo, S. S., Deng, J., Chiao, P., and Hung, M. C. (1997). Inhibition of nuclear factor-kappaB activity is involved in E1A-mediated sensitization of radiation-induced apoptosis. J Biol Chem 272, 32739-32742.
Shiraiwa, N., Inohara, N., Okada, S., Yuzaki, M., Shoji, S., and Ohta, S. (1996). An additional form of rat Bcl-x, Bcl-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells. J Biol Chem 271, 13258-13265.
Shisler, J., Duerksen-Hughes, P., Hermiston, T. M., Wold, W. S., and Gooding, L. R. (1996). Induction of susceptibility to tumor necrosis factor by E1A is dependent on binding to either p300 or p105-Rb and induction of DNA synthesis. J Virol 70, 68-77.
Siddik, Z. H. (2003). Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279.
Smardova, J., Pavlova, S., Svitakova, M., Grochova, D., and Ravcukova, B. (2005). Analysis of p53 status in human cell lines using a functional assay in yeast: detection of new non-sense p53 mutation in codon 124. Oncol Rep 14, 901-907.
Stephens, C., and Harlow, E. (1987). Differential splicing yields novel adenovirus 5 E1A mRNAs that encode 30 kd and 35 kd proteins. Embo J 6, 2027-2035.
Takehara, T., Liu, X., Fujimoto, J., Friedman, S. L., and Takahashi, H. (2001). Expression and role of Bcl-xL in human hepatocellular carcinomas. Hepatology 34, 55-61.
Takehara, T., and Takahashi, H. (2003). Suppression of Bcl-xL deamidation in human hepatocellular carcinomas. Cancer Res 63, 3054-3057.
Trimarchi, J. M., and Lees, J. A. (2002). Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3, 11-20.
Ulfendahl, P. J., Linder, S., Kreivi, J. P., Nordqvist, K., Sevensson, C., Hultberg, H., and Akusjarvi, G. (1987). A novel adenovirus-2 E1A mRNA encoding a protein with transcription activation properties. Embo J 6, 2037-2044.
Vaux, D. L., and Korsmeyer, S. J. (1999). Cell death in development. Cell 96, 245-254.
Weinberg, R. A. (1991). Tumor suppressor genes. Science 254, 1138-1146.
Weinberg, R. A. (1995). The retinoblastoma protein and cell cycle control. Cell 81, 323-330.
Whyte, P., Buchkovich, K. J., Horowitz, J. M., Friend, S. H., Raybuck, M., Weinberg, R. A., and Harlow, E. (1988). Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334, 124-129.
Yoshimoto, T., Uchino, H., He, Q. P., Li, P. A., and Siesjo, B. K. (2001). Cyclosporin A, but not FK506, prevents the downregulation of phosphorylated Akt after transient focal ischemia in the rat. Brain Res 899, 148-158.
Yu, D., Wolf, J. K., Scanlon, M., Price, J. E., and Hung, M. C. (1993). Enhanced c-erbB-2/neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A. Cancer Res 53, 891-898.
Yu, D. H., Scorsone, K., and Hung, M. C. (1991). Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene. Mol Cell Biol 11, 1745-1750.
Zafarullah, M., Li, W. Q., Sylvester, J., and Ahmad, M. (2003). Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 60, 6-20.
Zamble, D. B., and Lippard, S. J. (1995). Cisplatin and DNA repair in cancer chemotherapy. Trends Biochem Sci 20, 435-439.
Zhao, R., Yang, F. T., and Alexander, D. R. (2004). An oncogenic tyrosine kinase inhibits DNA repair and DNA-damage-induced Bcl-xL deamidation in T cell transformation. Cancer Cell 5, 37-49.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top