(3.235.245.219) 您好!臺灣時間:2021/05/07 21:23
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:賴吉慶
研究生(外文):Ji-Ching Lai
論文名稱:人類乳突病毒感染誘發ubiquitin蛋白表現和台灣不抽菸女性肺癌形成之相關性研究
論文名稱(外文):The association of induction of ubiquitin overexpression by human papillomavirus 16/18 with lung cancer among nonsmoking Taiwanese women
指導教授:李 輝
指導教授(外文):Huei Lee
學位類別:碩士
校院名稱:中山醫學院
系所名稱:毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:83
中文關鍵詞:人類乳突病毒肺癌
外文關鍵詞:ubiquitinHPVlung cancer
相關次數:
  • 被引用被引用:0
  • 點閱點閱:134
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
肺癌是台灣地區第一大癌症死亡原因,過去研究指出腫瘤形成通常是經由抑癌基因的突變和蛋白之不穩定而造成去活化所致。過去本研究室已發現肺癌患者發生p53基因的突變頻率遠較其他國家的肺癌為低。同時以免疫組織化學分析法偵測肺腫瘤中p53, p21WAF-1以及Rb蛋白有表現之頻率遠低於過去報告。已知ubiquitin proteasomal pathway參與蛋白的分解,因此本研究擬分析在肺腫瘤形成過程中ubiquitin蛋白是否過度表現而活化ubiquitin proteasomal pathway將p53、p21WAF-1蛋白去活化,因此本研究收集128個肺腫瘤和36個非癌症正常肺組織,以免疫組織染色法分析ubiquitin蛋白在肺組織的表現,結果發現肺癌患者之ubiquitin蛋白僅8個樣品為不表現或低表現,其餘皆為過度表現,而非癌症控制組沒有任何一個樣品為過度表現。因此肺腫瘤組織ubiquitin蛋白表現率明顯高於非癌症控制組 (P=0.001)。並由ubiquitin蛋白與p53、p21WAF-1蛋白表現分析,發現ubiquitin在肺腫瘤組織切片的表現與p53、p21WAF-1蛋白的消失有關,並利用proteasome inhibitor在肺癌細胞 (CL-3) 證實肺癌中p53與p21WAF-1蛋白是經由ubiquitin proteasome pathway所調控。
最近本研究室發現不抽菸女性肺癌患者之人類乳突狀病毒16、18型 (human papillomavirus 16/18, HPV 16/18)感染率顯著高於不抽菸和抽菸男性肺癌患者,同時又發現女性肺癌患者之p53突變頻率不到5%,但p53蛋白有70%無法以免疫染色偵測。因此推測HPV可能誘發ubiquitin蛋白表現,而將p53蛋白分解。故本研究以in situ RT-PCR分析肺癌中HPV 16/18 E6 mRNA表現、ubiquitin蛋白與p53蛋白的消失相關性,結果發現感染HPV 16有E6 mRNA表現的女性肺癌患者經由活化ubiquitin蛋白表現參與p53蛋白之去活化。經由ubiquitin proteosomal pathway來解釋p53蛋白去活化的女性肺癌患者僅有37% (10/27),在沒有HPV 16 E6 mRNA表現,而p53蛋白存在之女性患者有14.8% (4/27),因此可由HPV16感染而表現E6 mRNA的女性患者有一半以上之女性肺癌患者可由E6 活化ubiquitin proteosomal pathway來解釋p53蛋白之去活化。因此ubiquitin在肺腫瘤化過程中過度表現有部分原因是經由HPV感染所致。

Lung cancer is the leading cause of cancer death in Taiwanese women since 1982. Although less than 10% of female lung cancer patients are smokers, high lung cancer mortality ratio of male: female in Taiwan (2:1) was observed. The etiological factor remains unknown. We hypothesize that ubiquitin proteasome system may be associated with lung cancer development based on high prevalence of tumor suppressor gene (p53 or p21WAF-1) negative immunostainings in Taiwanese female lung cancer compared to male lung cancer. In this study, 128 lung tumor cases and 36 non-tumor controls were collected to examine ubiquitin protein expressions by immunohistochemistry. Our data indicated that frequencies of ubiquitin overexpression in lung tumor cases were significantly higher than in non-cancer controls (P=0.0001). To understand whether ubiquitin expression is associated with p53 and p21 inactivation, the immunostaining data of ubiquitin, p53 and p21 were analyzed. The reverse correlation between ubiquitin and p21WAF-1 and/or p53 protein was observed respectively (P=0.006 for p21WAF-1, P=0.237 for p53). To confirm the association, proteasome inhibitor MG-132 was used in lung cancer cell line CL-3 and western blot analysis data showed that p21 and p53 protein levels significantly increased in the addition of proteasome inhibitor MG-132. This result suggests that ubiquitin proteasomal pathway was involved in p21 and p53 protein degradation in lung cancer.
Our recent report indicated that high frequency of HPV 16/18 infection in Taiwanese non-smoking female lung cancer compared to non-smoking and smoking male lung cancer. Our preliminary data showed that high frequency of p53 negative immunostaining in female lung cancer was observed than male lung cancer. We hypothesize that HPV 16/18 E6 protein may be associated with p53 inactivation medicating through ubiquitin proteasomal pathway. Thus, the correlation between HPV 16/18 E6 mRNA expression and p53 immunostaining in lung tumors was statistically analyzed. The correlation was only observed in non-smoking female lung tumors. Our data showed that 10 of 27 (37%) of non-smoking female lung tumors with p53 negative immunostaining had HPV 16 E6 mRNA and ubiquitin positive expressions. On the contrast, 4 of 27 (14.8%) of non-smoking female lung tumors with p53 immunostaining did not have HPV 16 E6 mRNA and ubiquitin expressions. Therefore, high frequencies of p53 negative immunostainings in Taiwanese non-smoking female lung cancer patients may be associated with HPV 16 infection to cause ubiquitin proteasomal pathway activation.

目 錄
壹、中文摘要 1
貳、文獻綜論 3
一、p53抑癌蛋白結構與功能及在肺癌相關研究 3
二、p21WAF-1/CIP-1抑癌基因在結構與功能相關研究 4
三、Ubiquitin proteasome pathway 5
四、人類乳突狀病毒基本介紹 8
五、p53抑癌基因去活化相關研究 11
參、研究動機 14
肆、材料與方法 18
一、腫瘤組織 18
三、組織檢體來源 18
二、材料與藥品 19
四、免疫組織化學染色法 21
五、細胞培養 23
六、蛋白定量與分析 24
七、西方墨點法 24
八、DNA萃取與純化 26
九、基因多型性分析 27
十、統計分析 29
伍、結果與討論 30
一、肺癌與非癌症病患ubiquitin蛋白表現之比較 30
二、肺癌組織ubiquitin蛋白與p53、p21WAF-1蛋白
表現之相關性 32
三、肺癌組織ubiquitin蛋白與腫瘤抑制蛋白p53、
人類乳突狀病毒相關性 36
四、人類乳突狀病毒E6 mRNA對ubiquitin 細胞核
表現相關性 38
五、p21WAF-1抑癌基因與腫瘤相關性 41
陸、參考文獻 44
柒、圖與表 60
捌、英文摘要 81

Barak Y. Juven T. Haffner R. Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J.1993.12 (2): 461-8.
Beer-Romero P, Glass S, Rolfe M. Antisense targeting of E6AP elevates p53 in HPV-infected cells but not in normal cells. Oncogene 1997.14 (5): 595-602.
Blagosklonny MV, Wu GS, Omura S, El-Deiry WS. Proteasome-dependent regulation of p21WAF1/CIP1 expression. : Biochem Biophys Res Commun 1996. 227 (2): 564-9.
Bossola M, Muscaritoli M, Costelli P, Bellantone R, Pacelli F, Busquets S, Argiles J, Lopez-Soriano FJ, Civello IM, Baccino FM, Fanelli FR, Doglietto GB.Increased muscle ubiquitin mRNA levels in gastric cancer patientsAm J Physiol Regul Integr Comp Physiol. 2001. 280 (5): R1518-23.
Bond JA, Blaydes JP, Rowson J, Haughton MF, Smith JR, Wynford-Thomas D, Wyllie FS. Mutant p53 rescues human diploid cells from senescence without inhibiting the induction of SDI1/WAF1. Cancer Res 1995. 55 (11): 2404-9.
Brown JP, Pagano M. Mechanism of p53 degradation. Biochim Biophys Acta 1997. 1332 (2): O1-6.
Cayrol C, Ducommun B. Interaction with cyclin-dependent kinases and PCNA modulates proteasome-dependent degradation of p21. Oncogene 1998. 17 (19): 2437-44.
Chao Y, Shih YL, Chiu JH, Chau GY, Lui WY, Yang WK, Lee SD, Huang TS. Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepatocellular carcinoma. Cancer Res 1998. 58 (5): 985-90.
Chen L. Agrawal S. Zhou W. Zhang R. Chen J. Synergistic activation of p53 by inhibition of MDM2 expression and DNA damage. Proc. Natl. Acad. Sci. 1998 U.S.A. 95 (1): 195-200.
Chen CY. Oliner JD. Zhan Q. Fornace AJ Jr. Vogelstein B. Kastan MB. Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway. Proc. Natl. Acad. Sci. U.S.A. 1994 91 (7): 2684-8.
Chen J-T Inversely prognostic vaules of p21WAF-1/CIP1 focal and diffuse expressions in non-small cell lung cancer. 1998 Submitted.
Cheng YW, Chiou HL, Sheu GT, Hsieh LL, Chen JT, Chen CY, Su JM, Lee H. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res 2001. 61 (7): 2799-803.
Ciechanover A, Schwartz AL. The ubiquitin-mediated proteolytic pathway: mechanisms of recognition of the proteolytic substrate and involvement in the degradation of native cellular proteins. FASEB J 1994. 8 (2): 182-91.
Crook T, Ludwig RL, Marston NJ, Willkomm D, Vousden KH. Sensitivity of p53 lysine mutants to ubiquitin-directed degradation targeted by human papillomavirus E6. Virology 1996. 217 (1): 285-92.
Department of Healthy, The Executive Yuan Republic of China: General health statistics, in Healthy and Vital Statistics, Republic of China, Taipei, Twain, ROC, 1996, 88-111.
El-Deiry WS. Tokino T. Waldman T. Oliner JD. Velculescu VE. Burrell M. Hill DE. Healy E. Rees JL. Hamilton SR. et al. Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res. 1995 55 (13): 2910-9.
El-Deiry WS. Tokino T. Velculescu VE. Levy DB. Parsons R. Trent JM. Lin D. Mercer WE. Kinzler KW. Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 75 (4): 817-25.
Facher EA, Becich MJ, Deka A, Law JC. Association between human cancer and two polymorphisms occurring together in the p21Waf1/Cip1 cyclin-dependent kinase inhibitor gene. Cancer 1997. 79 (12): 2424-9.
Finlay CA. p53 loss of function: implications for the processes of immortalization and tumorigenesis. Bioessays 1992. 14 (8): 557-60.
Fukuchi K, Tomoyasu S, Nakamaki T, Tsuruoka N, Gomi K. DNA damage induces p21 protein expression by inhibiting ubiquitination in ML-1 cells. Biochim Biophys Acta 1998. 1404 (3): 405-11.
Gao YT. Blot WJ. Zheng W. Ershow AG. Hsu CW. Levin LI. Zhang R. Fraumeni JF Jr. Lung cancer among Chinese women. Int. J. Cancer 1987 40 (5): 604-9, 87.
Greenblatt MS. Bennett WP. Hollstein M. Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994 54 (18): 4855-78.
Govers R, ten Broeke T, van Kerkhof P, Schwartz AL, Strous GJ. Identification of a novel ubiquitin conjugation motif, required for ligand-induced internalization of the growth hormone receptor. EMBO J. 1999. 18 (1): 28-36.
Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J, Slingerland J, Krek W. Skp2 is oncogenic and overexpressed in human cancers. Proc Natl Acad Sci U S A 2001. 98 (9): 5043-8.
Harris CC. Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. J. Natl. Cancer Inst. 88 (20): 1442-55, 1996.
Hershko A, Ganoth D, Sudakin V, Dahan A, Cohen LH, Luca FC, Ruderman JV, Eytan E. Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2. J. Biol Chem 1994. 269 (7): 4940-6.
Hicke L.Gettin' down with ubiquitin: turning off cell-surface receptors, transporters and channels. Trends Cell Biol 1999. 9 (3): 107-12.
Hildesheim A, Schiffman MH, Gravitt PE et al. Persistence of type-specific human papillomaviurs infection among cytologically normal women, J Infect Dis.1994; 169:235-40.
Hiro-omi Kanayama, Keiji Tanaka, Masashi Aki, Susumu Kagawa, Hiromasa Miyaji, Mitsuo Satoh, Fumio Okada, Seiji Sato, Naoki Shimbara, and Akira Ichihara.:Change in Expressions of Proteasome and Ubiquitin Genes in Human Renal Cancer Cells. Cancer Resescher, 1991, 51, 6677-6685.
Hochstrasser M. Protein degradation or regulation: Ub the judge. Cell 1996. 84 (6): 813-5.
Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 1997. 420 (1): 25-7.
Hussain SP. Harris CC. Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res. 1998 58 (18): 4023-37.
Jentsch S, Schlenker S. Selective protein degradation: a journey's end within the proteasome. Cell 1995. 82 (6): 881-4.
Kanayama H, Tanaka K, Aki M, Kagawa S, Miyaji H, Satoh M, Okada F, Sato S, Shimbara N, Ichihara A. Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells. Cancer Res 1991. 51 (24): 6677-85.
Kastan MB. Onyekwere O. Sidransky D. Vogelstein B. Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51 1991 (23 Pt 1): 6304-11.
Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ Jr. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 1992. 71 (4): 587-97.
King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 1995. 81 (2): 279-88.
Koo LC, Ho JH. Worldwide epidemiological patterns of lung cancer in nonsmokers. Int J Epidemiol 1990; 19 Suppl 1:S14-23.
Kotani S, Tanaka H, Yasuda H, Todokoro K. Regulation of APC activity by phosphorylation and regulatory factors. J Cell Biol 1999 Aug 23; 146 (4): 791-800.
Kuan-Ying Yu. Gender differences in p53 gene mutation, p53, mdm2 protein expressions and mdm2 splicing transcripts in Taiwanese non-small lung cancer patients. 2000 Master Thesis
Lane DP. Cancer. P53, guardian of the genome. Nature. 358 (6381): 15-6, 1992.
Laney JD. Hochstrasser M. Substrate targeting in the ubiquitin system. [Review] [25 refs] Cell. 1999 97 (4): 427-30.
Leptak C, Ramon y Cajal S, Kulke R, Horwitz BH, Riese DJ 2nd, Dotto GP, DiMaio D. Tumorigenic transformation of murine keratinocytes by the E5 genes of bovine papillomavirus type 1 and human papillomavirus type 16. J. Virol 1991. 65 (12): 7078-83.
Levine AJ. P53, the cellular gatekeeper for growth and division. Cell 1997 Feb 7; 88 (3): 323-31.
You J, Pickart CM. A hect domain e3 enzyme assembles novel polyubiquitin chains. J Biol Chem 2001. 276 (23): 19871-8.
Li X, Coffino P. High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation. J Virol 1996. 70 (7): 4509-16.
Lukas J, Groshen S, Saffari B, Niu N, Reles A, Wen WH, Felix J, Jones LA, Hall FL, Press MF. WAF1/Cip1 gene polymorphism and expression in carcinomas of the breast, ovary, and endometrium. Am J Pathol 1997. 150 (1): 167-75.
Lu X. Lane DP. Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell. 1993 75 (4): 765-78.
Macri E, Loda M. Role of p27 in prostate carcinogenesis. Cancer Metastasis Rev 1998-99; 17 (4): 337-44.
Maki CG, Huibregtse JM, Howley PM. In vivo ubiquitination and proteasome-mediated degradation of p53 (1). Cancer Res 1996. 56 (11): 2649-54
Maltzman W. Czyzyk L. UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol. Cell. Biol. 1984 4 (9): 1689-94.
Marchetti A, Doglioni C, Barbareschi M, Buttitta F, Pellegrini S, Bertacca G, Chella A, Merlo G, Angeletti CA, Dalla Palma P, Bevilacqua G. p21 RNA and protein expression in non-small cell lung carcinomas: evidence of p53-independent expression and association with tumoral differentiation Oncogene 1996. 12 (6): 1319-24.
Mark Rolfe, M.Isable Chiu, Michele Pagano: The ubiquitin-mediated proteolytic pathway as a therapeutic area. J Mol Med 1997, 75:5-17.
McLaughlin PM, Helfrich W, Kok K, Mulder M, Hu SW, Brinker MG, Ruiters MH, de Leij LF, Buys CH. The ubiquitin-activating enzyme E1-like protein in lung cancer cell lines. Int. J. Cancer 2000. 85 (6): 871-6.
Michieli P, Chedid M, Lin D, Pierce JH, Mercer WE, Givol D. Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res 1994. 54 (13): 3391-5.
Mimnaugh EG, Chen HY, Davie JR, Celis JE, Neckers L. Rapid deubiquitination of nucleosomal histones in human tumor cells caused by proteasome inhibitors and stress response inducers: effects on replication, transcription, translation, and the cellular stress response. Biochemistry 1997. 36 (47): 14418-29.
Miyashita T. Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995 80 (2): 293-9.
Momand J, Wu HH, Dasgupta G. MDM2--master regulator of the p53 tumor suppressor protein. Gene 2000. 242 (1-2): 15-29.
Moll UM, Riou G, Levine AJ. Moll UM, Riou G, Levine AJ. Proc Natl Acad Sci U S A 1992. 89 (15): 7262-6.
Moro A, Perea SE, Pantoja C, Santos A, Arana MD, Serrano IFNalpha 2b induces apoptosis and proteasome-mediated degradation of p27Kip1 in a human lung cancer cell line. Oncol Rep 2001. 8 (2): 425-9.
Okamoto K, Beach D. Cyclin G is a transcriptional target of the p53 tumor suppressor protein. EMBO J. 1994. 13 (20): 4816-22.
Oliner JD. Pietenpol JA. Thiagalingam S. Gyuris J. Kinzler KW. Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993 362 (6423): 857-60.
Orian A, Whiteside S, Israel A, Stancovski I, Schwartz AL, Ciechanover A. Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105. Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation. J Biol Chem 1995. 270 (37): 21707-14.
Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell 1994. 78 (5): 773-85.
Palefsky JM, Holly EA. Molecular virology and epidemiology of human papillomavirus and cervical cancer. Cancer Epidemiol Biomarkers Prev 1995. (4): 415-28.
Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ. P53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science 1995. 267 (5200): 1024-7.
Parkin DM, Pisani P, Ferlay. J Estimates of the worldwide mortality form eighteen major cancer in 1985. Implication for prevention and projections of future burden. J Int 1993; 55:891-903.
Piccini A, Storey A, Massimi P, Banks L. Mutations in the human papillomavirus type 16 E2 protein identify multiple regions of the protein involved in binding to E1. J Gen Virol 1995. 76 (Pt 11): 2909-13.
Pim D, Collins M, Banks L. Human papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor. Oncogene 1992. (1): 27-32.
Reihsaus E, Kohler M, Kraiss S, Oren M, Montenarh M. Regulation of the level of the oncoprotein p53 in non-transformed and transformed cells. Oncogene 1990. 5 (1): 137-45.
Sarnow P, Ho YS, Williams J, Levine AJ. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell 1982. 28(2): 387-94.
Scheffner M. Ubiquitin, E6-AP, and their role in p53 inactivation. Pharmacol Ther 1998. 78(3): 129-39.
Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proc Natl Acad Sci U S A 1995. 92 (24): 11259-63.
Schlegel R, Phelps WC, Zhang YL, Barbosa M. Quantitative keratinocyte assay detects two biological activities of Human. Papollomavirus DNA and identifies viral types associated with cervical carcinomas. EMBO J. 1988. 7 (10): 3181-7.
Selvakumaran M. Lin HK. Miyashita T. Wang HG. Krajewski S. Reed JC. Hoffman B. Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene. 9 (6): 1791-8, 1994.
Shih CM, Lin PT, Wang HC, Huang WC, Wang YC. Lack of evidence of association of p21WAF1/CIP1 polymorphism with lung cancer susceptibility and prognosis in Taiwan. Jpn J Cancer Res 2000. 91 (1): 9-15.
Shimizu T, Miwa W, Nakamori S, Ishikawa O, Konishi Y, Sekiya T. Absence of a mutation of the p21/WAF1 gene in human lung and pancreatic cancers. Jpn J Cancer Res 1996. 87 (3): 275-8.
Slingerland J, Pagano M. Regulation of the cdk inhibitor p27 and its deregulation in cancer. J Cell Physiol 2000. 183 (1): 10-7.
Smith SE. Koegl M. Jentsch S. Role of the ubiquitin/proteasome system in regulated protein degradation in Saccharomyces cerevisiae. [Review] [107 refs] Biological Chemistry. 1996 377 (7-8): 437-46.
Soini Y, Nuorva K, Kamel D, Pollanen R, Vahakangas K, Lehto VP, Paakko P. Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma. Thorax 1996. 51 (9): 887-93.
Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J, Luca FC, Ruderman JV, Hershko A. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell 1995. 6 (2): 185-97.
Srivenugopal KS, Yuan XH, Friedman HS, Ali-Osman F. Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltransferase in human and murine tumor cells following inactivation with O6-benzylguanine or 1,3-bis (2-chloroethyl)-1-nitrosourea. Biochemistry 1996. 35 (4): 1328-34.
Stancovski I, Gonen H, Orian A, Schwartz AL, Ciechanover A. Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic system in vivo and in vitro: identification and characterization of the conjugating enzymes. Mol Cell Biol 1995. 15 (12): 7106-16.
Strous GJ, Govers R. The ubiquitin-proteasome system and endocytosis. J Cell Sci 1999. 112 (Pt 10): 1417-23.
Takahashi T. Takahashi T. Suzuki H. Hida T. Sekido Y. Ariyoshi Y. Ueda R. The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern. Oncogene 1991.6 (10): 1775-8.
Takagi Y, Koo LC, Osada H, Ueda R, Kyaw K, Ma CC, Suyama M, Saji S, Takahashi T, Tominaga S, et al. Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women in Hong Kong. Cancer Res 1995. 55 (22): 5354-7.
Talis AL, Huibregtse JM, Howley PM. The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells J Biol Chem 1998. 273(11): 6439-45.
Treier M, Staszewski LM, Bohmann D. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain. Cell 1994. 78 (5): 787-98.
Tsurumi C, Ishida N, Tamura T, Kakizuka A, Nishida E, Okumura E, Kishimoto T, Inagaki M, Okazaki K, Sagata N, et al. Degradation of c-Fos by the 26S proteasome is accelerated by c-Jun and multiple protein kinases. Mol Cell Biol 1995. 15 (10): 5682-7.
Vali U, Kilk A, Ustav M. Bovine papillomavirus oncoprotein E5 affects the arachidonic acid metabolism in cells. Int J Biochem Cell Biol 2001. 33 (3): 227-35.
Xi LF, Demers GW, Koutskv LA et al. Analysis of human papillomairus type 16 variant indicates establishment of persistent infection. J Infect Dis 1995; 172:747-55.
Zur Hausen H. Human pathogenic papillomaviruses. Berlin: Springer-Verlag, 1994:83-100.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔