請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40578完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 葉秀慧 | |
| dc.contributor.author | Min-Ju Lu | en |
| dc.contributor.author | 盧珉如 | zh_TW |
| dc.date.accessioned | 2021-06-14T16:51:59Z | - |
| dc.date.available | 2013-08-08 | |
| dc.date.copyright | 2008-08-08 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-29 | |
| dc.identifier.citation | [1] D. M. Parkin, F. Bray, J. Ferlay, and P. Pisani, 'Estimating the world cancer burden: Globocan 2000,' Int J Cancer, vol. 94, pp. 153-6, Oct 15 2001.
[2] C. J. Chen, M. W. Yu, and Y. F. Liaw, 'Epidemiological characteristics and risk factors of hepatocellular carcinoma,' J Gastroenterol Hepatol, vol. 12, pp. S294-308, Oct 1997. [3] P. J. Chen and D. S. Chen, 'Hepatitis B virus infection and hepatocellular carcinoma: molecular genetics and clinical perspectives,' Semin Liver Dis, vol. 19, pp. 253-62, 1999. [4] W. R. Kim, R. S. Brown, Jr., N. A. Terrault, and H. El-Serag, 'Burden of liver disease in the United States: summary of a workshop,' Hepatology, vol. 36, pp. 227-42, Jul 2002. [5] K. Hatanaka, M. Kudo, T. Fukunaga, K. Ueshima, H. Chung, Y. Minami, Y. Sakaguchi, S. Hagiwara, A. Orino, and Y. Osaki, 'Clinical characteristics of NonBNonC- HCC: Comparison with HBV and HCV related HCC,' Intervirology, vol. 50, pp. 24-31, 2007. [6] K. Maekawa, N. Imagawa, M. Nagamatsu, and S. Harada, 'Molecular cloning of a novel protein-tyrosine phosphatase containing a membrane-binding domain and GLGF repeats,' FEBS Lett, vol. 337, pp. 200-6, Jan 10 1994. [7] J. Saras, L. Claesson-Welsh, C. H. Heldin, and L. J. Gonez, 'Cloning and characterization of PTPL1, a protein tyrosine phosphatase with similarities to cytoskeletal-associated proteins,' J Biol Chem, vol. 269, pp. 24082-9, Sep 30 1994. [8] D. Banville, S. Ahmad, R. Stocco, and S. H. Shen, 'A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases,' J Biol Chem, vol. 269, pp. 22320-7, Sep 2 1994. [9] T. Sato, S. Irie, S. Kitada, and J. C. Reed, 'FAP-1: a protein tyrosine phosphatase that associates with Fas,' Science, vol. 268, pp. 411-5, Apr 21 1995. [10] F. D. Ciccarelli, P. Bork, and E. Kerkhoff, 'The KIND module: a putative signalling domain evolved from the C lobe of the protein kinase fold,' Trends Biochem Sci, vol. 28, pp. 349-52, Jul 2003. [11] A. H. Chishti, A. C. Kim, S. M. Marfatia, M. Lutchman, M. Hanspal, H. Jindal, S. C. Liu, P. S. Low, G. A. Rouleau, N. Mohandas, J. A. Chasis, J. G. Conboy, P. Gascard, Y. Takakuwa, S. C. Huang, E. J. Benz, Jr., A. Bretscher, R. G. Fehon, J. F. Gusella, V. Ramesh, F. Solomon, V. T. Marchesi, S. Tsukita, K. B. Hoover, and et al., 'The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane,' Trends Biochem Sci, vol. 23, pp. 281-2, Aug 1998. [12] M. A. Pearson, D. Reczek, A. Bretscher, and P. A. Karplus, 'Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain,' Cell, vol. 101, pp. 259-70, Apr 28 2000. [13] K. Hamada, T. Shimizu, T. Matsui, S. Tsukita, and T. Hakoshima, 'Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain,' EMBO J, vol. 19, pp. 4449-62, Sep 1 2000. [14] L. Herrmann, T. Dittmar, and K. S. Erdmann, 'The protein tyrosine phosphatase PTP-BL associates with the midbody and is involved in the regulation of cytokinesis,' Mol Biol Cell, vol. 14, pp. 230-40, Jan 2003. [15] E. Cuppen, M. van Ham, B. Pepers, B. Wieringa, and W. Hendriks, 'Identification and molecular characterization of BP75, a novel bromodomain-containing protein,' FEBS Lett, vol. 459, pp. 291-8, Oct 15 1999. [16] K. Maekawa, N. Imagawa, A. Naito, S. Harada, O. Yoshie, and S. Takagi, 'Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats,' Biochem J, vol. 337 ( Pt 2), pp. 179-84, Jan 15 1999. [17] S. Irie, T. Hachiya, S. Rabizadeh, W. Maruyama, J. Mukai, Y. Li, J. C. Reed, D. E. Bredesen, and T. A. Sato, 'Functional interaction of Fas-associated phosphatase-1 (FAP-1) with p75(NTR) and their effect on NF-kappaB activation,' FEBS Lett, vol. 460, pp. 191-8, Oct 29 1999. [18] E. Cuppen, H. Gerrits, B. Pepers, B. Wieringa, and W. Hendriks, 'PDZ motifs in PTP-BL and RIL bind to internal protein segments in the LIM domain protein RIL,' Mol Biol Cell, vol. 9, pp. 671-83, Mar 1998. [19] K. K. Murthy, K. Clark, Y. Fortin, S. H. Shen, and D. Banville, 'ZRP-1, a zyxin-related protein, interacts with the second PDZ domain of the cytosolic protein tyrosine phosphatase hPTP1E,' J Biol Chem, vol. 274, pp. 20679-87, Jul 16 1999. [20] E. Cuppen, M. van Ham, D. G. Wansink, A. de Leeuw, B. Wieringa, and W. Hendriks, 'The zyxin-related protein TRIP6 interacts with PDZ motifs in the adaptor protein RIL and the protein tyrosine phosphatase PTP-BL,' Eur J Cell Biol, vol. 79, pp. 283-93, Apr 2000. [21] C. Gross, R. Heumann, and K. S. Erdmann, 'The protein kinase C-related kinase PRK2 interacts with the protein tyrosine phosphatase PTP-BL via a novel PDZ domain binding motif,' FEBS Lett, vol. 496, pp. 101-4, May 11 2001. [22] S. Vincent and J. Settleman, 'The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization,' Mol Cell Biol, vol. 17, pp. 2247-56, Apr 1997. [23] M. van Ham, H. Croes, J. Schepens, J. Fransen, B. Wieringa, and W. Hendriks, 'Cloning and characterization of mCRIP2, a mouse LIM-only protein that interacts with PDZ domain IV of PTP-BL,' Genes Cells, vol. 8, pp. 631-44, Jul 2003. [24] J. Saras, P. Franzen, P. Aspenstrom, U. Hellman, L. J. Gonez, and C. H. Heldin, 'A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1,' J Biol Chem, vol. 272, pp. 24333-8, Sep 26 1997. [25] D. Lin, G. D. Gish, Z. Songyang, and T. Pawson, 'The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif,' J Biol Chem, vol. 274, pp. 3726-33, Feb 5 1999. [26] P. Zimmermann, K. Meerschaert, G. Reekmans, I. Leenaerts, J. V. Small, J. Vandekerckhove, G. David, and J. Gettemans, 'PIP(2)-PDZ domain binding controls the association of syntenin with the plasma membrane,' Mol Cell, vol. 9, pp. 1215-25, Jun 2002. [27] A. Palmer, M. Zimmer, K. S. Erdmann, V. Eulenburg, A. Porthin, R. Heumann, U. Deutsch, and R. Klein, 'EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP-BL phosphatase,' Mol Cell, vol. 9, pp. 725-37, Apr 2002. [28] K. S. Erdmann, 'The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions,' Eur J Biochem, vol. 270, pp. 4789-98, Dec 2003. [29] K. S. Erdmann, J. Kuhlmann, V. Lessmann, L. Herrmann, V. Eulenburg, O. Muller, and R. Heumann, 'The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain,' Oncogene, vol. 19, pp. 3894-901, Aug 10 2000. [30] V. N. Ivanov, P. Lopez Bergami, G. Maulit, T. A. Sato, D. Sassoon, and Z. Ronai, 'FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface,' Mol Cell Biol, vol. 23, pp. 3623-35, May 2003. [31] G. Bompard, C. Puech, C. Prebois, F. Vignon, and G. Freiss, 'Protein-tyrosine phosphatase PTPL1/FAP-1 triggers apoptosis in human breast cancer cells,' J Biol Chem, vol. 277, pp. 47861-9, Dec 6 2002. [32] T. Miyazaki, Y. Atarashi, S. Yasumura, I. Minatoya, K. Ogawa, M. Iwamoto, M. Minemura, Y. Shimizu, T. A. Sato, A. Watanabe, and T. Sugiyama, 'Fas-associated phosphatase-1 promotes Fas-mediated apoptosis in human colon cancer cells: novel function of FAP-1,' J Gastroenterol Hepatol, vol. 21, pp. 84-91, Jan 2006. [33] M. A. Buendia, 'Genetics of hepatocellular carcinoma,' Semin Cancer Biol, vol. 10, pp. 185-200, Jun 2000. [34] N. Kusano, K. Shiraishi, K. Kubo, A. Oga, K. Okita, and K. Sasaki, 'Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: their relationship to clinicopathological features,' Hepatology, vol. 29, pp. 1858-62, Jun 1999. [35] P. Laurent-Puig, P. Legoix, O. Bluteau, J. Belghiti, D. Franco, F. Binot, G. Monges, G. Thomas, P. Bioulac-Sage, and J. Zucman-Rossi, 'Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis,' Gastroenterology, vol. 120, pp. 1763-73, Jun 2001. [36] A. Marchio, P. Pineau, M. Meddeb, B. Terris, P. Tiollais, A. Bernheim, and A. Dejean, 'Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients,' Oncogene, vol. 19, pp. 3733-8, Aug 3 2000. [37] H. Okabe, I. Ikai, K. Matsuo, S. Satoh, H. Momoi, T. Kamikawa, N. Katsura, R. Nishitai, O. Takeyama, M. Fukumoto, and Y. Yamaoka, 'Comprehensive allelotype study of hepatocellular carcinoma: potential differences in pathways to hepatocellular carcinoma between hepatitis B virus-positive and -negative tumors,' Hepatology, vol. 31, pp. 1073-9, May 2000. [38] V. Boige, P. Laurent-Puig, P. Fouchet, J. F. Flejou, G. Monges, P. Bedossa, P. Bioulac-Sage, F. Capron, A. Schmitz, S. Olschwang, and G. Thomas, 'Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype,' Cancer Res, vol. 57, pp. 1986-90, May 15 1997. [39] A. Marchio, M. Meddeb, P. Pineau, G. Danglot, P. Tiollais, A. Bernheim, and A. Dejean, 'Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization,' Genes Chromosomes Cancer, vol. 18, pp. 59-65, Jan 1997. [40] H. Nagai, P. Pineau, P. Tiollais, M. A. Buendia, and A. Dejean, 'Comprehensive allelotyping of human hepatocellular carcinoma,' Oncogene, vol. 14, pp. 2927-33, Jun 19 1997. [41] S. H. Yeh, P. J. Chen, M. Y. Lai, and D. S. Chen, 'Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma: association with elevated alpha-fetoprotein production,' Gastroenterology, vol. 110, pp. 184-92, Jan 1996. [42] S. H. Yeh, D. C. Wu, C. Y. Tsai, T. J. Kuo, W. C. Yu, Y. S. Chang, C. L. Chen, C. F. Chang, D. S. Chen, and P. J. Chen, 'Genetic characterization of fas-associated phosphatase-1 as a putative tumor suppressor gene on chromosome 4q21.3 in hepatocellular carcinoma,' Clin Cancer Res, vol. 12, pp. 1097-108, Feb 15 2006. [43] M. Dromard, G. Bompard, M. Glondu-Lassis, C. Puech, D. Chalbos, and G. Freiss, 'The putative tumor suppressor gene PTPN13/PTPL1 induces apoptosis through insulin receptor substrate-1 dephosphorylation,' Cancer Res, vol. 67, pp. 6806-13, Jul 15 2007. [44] J. H. Zhu, R. Chen, W. Yi, G. T. Cantin, C. Fearns, Y. Yang, J. R. Yates, 3rd, and J. D. Lee, 'Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signaling,' Oncogene, vol. 27, pp. 2525-31, Apr 17 2008. [45] R. Moll, W. W. Franke, D. L. Schiller, B. Geiger, and R. Krepler, 'The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells,' Cell, vol. 31, pp. 11-24, Nov 1982. [46] H. Herrmann and U. Aebi, 'Intermediate filaments and their associates: multi-talented structural elements specifying cytoarchitecture and cytodynamics,' Curr Opin Cell Biol, vol. 12, pp. 79-90, Feb 2000. [47] N. O. Ku, P. Strnad, B. H. Zhong, G. Z. Tao, and M. B. Omary, 'Keratins let liver live: Mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies,' Hepatology, vol. 46, pp. 1639-49, Nov 2007. [48] M. B. Omary, P. A. Coulombe, and W. H. McLean, 'Intermediate filament proteins and their associated diseases,' N Engl J Med, vol. 351, pp. 2087-100, Nov 11 2004. [49] N. O. Ku, J. M. Darling, S. M. Krams, C. O. Esquivel, E. B. Keeffe, R. K. Sibley, Y. M. Lee, T. L. Wright, and M. B. Omary, 'Keratin 8 and 18 mutations are risk factors for developing liver disease of multiple etiologies,' Proc Natl Acad Sci U S A, vol. 100, pp. 6063-8, May 13 2003. [50] N. O. Ku, T. L. Wright, N. A. Terrault, R. Gish, and M. B. Omary, 'Mutation of human keratin 18 in association with cryptogenic cirrhosis,' J Clin Invest, vol. 99, pp. 19-23, Jan 1 1997. [51] N. O. Ku, J. K. Lim, S. M. Krams, C. O. Esquivel, E. B. Keeffe, T. L. Wright, D. A. Parry, and M. B. Omary, 'Keratins as susceptibility genes for end-stage liver disease,' Gastroenterology, vol. 129, pp. 885-93, Sep 2005. [52] P. Strnad, T. C. Lienau, G. Z. Tao, L. C. Lazzeroni, F. Stickel, D. Schuppan, and M. B. Omary, 'Keratin variants associate with progression of fibrosis during chronic hepatitis C infection,' Hepatology, vol. 43, pp. 1354-63, Jun 2006. [53] N. O. Ku, S. Michie, R. G. Oshima, and M. B. Omary, 'Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant,' J Cell Biol, vol. 131, pp. 1303-14, Dec 1995. [54] K. Zatloukal, S. W. French, C. Stumptner, P. Strnad, M. Harada, D. M. Toivola, M. Cadrin, and M. B. Omary, 'From Mallory to Mallory-Denk bodies: what, how and why?,' Exp Cell Res, vol. 313, pp. 2033-49, Jun 10 2007. [55] N. O. Ku, R. Gish, T. L. Wright, and M. B. Omary, 'Keratin 8 mutations in patients with cryptogenic liver disease,' N Engl J Med, vol. 344, pp. 1580-7, May 24 2001. [56] W. W. Franke, H. Denk, E. Schmid, M. Osborn, and K. Weber, 'Ultrastructural, biochemical, and immunologic characterization of Mallory bodies in livers of griseofulvin-treated mice. Fimbriated rods of filaments containing prekeratin-like polypeptides,' Lab Invest, vol. 40, pp. 207-20, Feb 1979. [57] L. Nan, F. Bardag-Gorce, Y. Wu, J. Li, B. A. French, and S. W. French, 'Mallory body forming cells express the preneoplastic hepatocyte phenotype,' Exp Mol Pathol, vol. 80, pp. 109-18, Apr 2006. [58] N. F. Bence, R. M. Sampat, and R. R. Kopito, 'Impairment of the ubiquitin-proteasome system by protein aggregation,' Science, vol. 292, pp. 1552-5, May 25 2001. [59] Q. X. Yuan, N. Marceau, B. A. French, P. Fu, and S. W. French, 'Mallory body induction in drug-primed mouse liver,' Hepatology, vol. 24, pp. 603-12, Sep 1996. [60] H. Denk, F. Gschnait, and K. Wolff, 'Hepatocellar hyalin (Mallory bodies) in long term griseofulvin-treated mice: a new experimental model for the study of hyalin formation,' Lab Invest, vol. 32, pp. 773-6, Jun 1975. [61] H. Yokoo, T. R. Harwood, D. Racker, and S. Arak, 'Experimental production of Mallory bodies in mice by diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine,' Gastroenterology, vol. 83, pp. 109-13, Jul 1982. [62] K. Zatloukal, C. Stumptner, M. Lehner, H. Denk, H. Baribault, L. G. Eshkind, and W. W. Franke, 'Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies,' Am J Pathol, vol. 156, pp. 1263-74, Apr 2000. [63] I. Nakamichi, D. M. Toivola, P. Strnad, S. A. Michie, R. G. Oshima, H. Baribault, and M. B. Omary, 'Keratin 8 overexpression promotes mouse Mallory body formation,' J Cell Biol, vol. 171, pp. 931-7, Dec 19 2005. [64] C. Stumptner, M. B. Omary, P. Fickert, H. Denk, and K. Zatloukal, 'Hepatocyte cytokeratins are hyperphosphorylated at multiple sites in human alcoholic hepatitis and in a mallory body mouse model,' Am J Pathol, vol. 156, pp. 77-90, Jan 2000. [65] P. Strnad, M. Harada, M. Siegel, R. A. Terkeltaub, R. M. Graham, C. Khosla, and M. B. Omary, 'Transglutaminase 2 regulates mallory body inclusion formation and injury-associated liver enlargement,' Gastroenterology, vol. 132, pp. 1515-26, Apr 2007. [66] C. Stumptner, A. Fuchsbichler, H. Heid, K. Zatloukal, and H. Denk, 'Mallory body--a disease-associated type of sequestosome,' Hepatology, vol. 35, pp. 1053-62, May 2002. [67] D. M. Toivola, G. Z. Tao, A. Habtezion, J. Liao, and M. B. Omary, 'Cellular integrity plus: organelle-related and protein-targeting functions of intermediate filaments,' Trends Cell Biol, vol. 15, pp. 608-17, Nov 2005. [68] S. Kim and P. A. Coulombe, 'Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm,' Genes Dev, vol. 21, pp. 1581-97, Jul 1 2007. [69] P. A. Coulombe, O. Bousquet, L. Ma, S. Yamada, and D. Wirtz, 'The 'ins' and 'outs' of intermediate filament organization,' Trends Cell Biol, vol. 10, pp. 420-8, Oct 2000. [70] M. B. Omary, N. O. Ku, J. Liao, and D. Price, 'Keratin modifications and solubility properties in epithelial cells and in vitro,' Subcell Biochem, vol. 31, pp. 105-40, 1998. [71] I. Izawa and M. Inagaki, 'Regulatory mechanisms and functions of intermediate filaments: a study using site- and phosphorylation state-specific antibodies,' Cancer Sci, vol. 97, pp. 167-74, Mar 2006. [72] M. Inagaki, Y. Nishi, K. Nishizawa, M. Matsuyama, and C. Sato, 'Site-specific phosphorylation induces disassembly of vimentin filaments in vitro,' Nature, vol. 328, pp. 649-52, Aug 13-19 1987. [73] M. Inagaki, Y. Gonda, K. Nishizawa, S. Kitamura, C. Sato, S. Ando, K. Tanabe, K. Kikuchi, S. Tsuiki, and Y. Nishi, 'Phosphorylation sites linked to glial filament disassembly in vitro locate in a non-alpha-helical head domain,' J Biol Chem, vol. 265, pp. 4722-9, Mar 15 1990. [74] M. Inagaki, Y. Gonda, M. Matsuyama, K. Nishizawa, Y. Nishi, and C. Sato, 'Intermediate filament reconstitution in vitro. The role of phosphorylation on the assembly-disassembly of desmin,' J Biol Chem, vol. 263, pp. 5970-8, Apr 25 1988. [75] T. Yano, T. Tokui, Y. Nishi, K. Nishizawa, M. Shibata, K. Kikuchi, S. Tsuiki, T. Yamauchi, and M. Inagaki, 'Phosphorylation of keratin intermediate filaments by protein kinase C, by calmodulin-dependent protein kinase and by cAMP-dependent protein kinase,' Eur J Biochem, vol. 197, pp. 281-90, Apr 23 1991. [76] M. Peter, J. Nakagawa, M. Doree, J. C. Labbe, and E. A. Nigg, 'In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase,' Cell, vol. 61, pp. 591-602, May 18 1990. [77] E. Fuchs and D. W. Cleveland, 'A structural scaffolding of intermediate filaments in health and disease,' Science, vol. 279, pp. 514-9, Jan 23 1998. [78] D. M. Toivola, N. O. Ku, E. Z. Resurreccion, D. R. Nelson, T. L. Wright, and M. B. Omary, 'Keratin 8 and 18 hyperphosphorylation is a marker of progression of human liver disease,' Hepatology, vol. 40, pp. 459-66, Aug 2004. [79] K. Zatloukal, C. Stumptner, A. Fuchsbichler, P. Fickert, C. Lackner, M. Trauner, and H. Denk, 'The keratin cytoskeleton in liver diseases,' J Pathol, vol. 204, pp. 367-76, Nov 2004. [80] P. A. Coulombe and M. B. Omary, ''Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments,' Curr Opin Cell Biol, vol. 14, pp. 110-22, Feb 2002. [81] N. O. Ku, S. A. Michie, R. M. Soetikno, E. Z. Resurreccion, R. L. Broome, and M. B. Omary, 'Mutation of a major keratin phosphorylation site predisposes to hepatotoxic injury in transgenic mice,' J Cell Biol, vol. 143, pp. 2023-32, Dec 28 1998. [82] L. Wells, K. Vosseller, and G. W. Hart, 'Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc,' Science, vol. 291, pp. 2376-8, Mar 23 2001. [83] H. Denk, C. Stumptner, and K. Zatloukal, 'Mallory bodies revisited,' J Hepatol, vol. 32, pp. 689-702, Apr 2000. [84] E. Candi, E. Tarcsa, J. J. Digiovanna, J. G. Compton, P. M. Elias, L. N. Marekov, and P. M. Steinert, 'A highly conserved lysine residue on the head domain of type II keratins is essential for the attachment of keratin intermediate filaments to the cornified cell envelope through isopeptide crosslinking by transglutaminases,' Proc Natl Acad Sci U S A, vol. 95, pp. 2067-72, Mar 3 1998. [85] N. O. Ku and M. B. Omary, 'Keratins turn over by ubiquitination in a phosphorylation-modulated fashion,' J Cell Biol, vol. 149, pp. 547-52, May 1 2000. [86] N. O. Ku and M. B. Omary, 'Effect of mutation and phosphorylation of type I keratins on their caspase-mediated degradation,' J Biol Chem, vol. 276, pp. 26792-8, Jul 20 2001. [87] R. G. Oshima, H. Baribault, and C. Caulin, 'Oncogenic regulation and function of keratins 8 and 18,' Cancer Metastasis Rev, vol. 15, pp. 445-71, Dec 1996. [88] M. Harada, P. Strnad, E. Z. Resurreccion, N. O. Ku, and M. B. Omary, 'Keratin 18 overexpression but not phosphorylation or filament organization blocks mouse Mallory body formation,' Hepatology, vol. 45, pp. 88-96, Jan 2007. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40578 | - |
| dc.description.abstract | Fas-associated phosphatase-1 (FAP-1)基因屬於protein tyrosine phosphatase的一員。根據本實驗室先前之位置選殖研究指出，FAP-1有可能是位於染色體4q21-23上之一可能參與肝癌之腫瘤抑制基因，但其參與肝癌過程真正的功能角色仍未釐清。
因為FAP-1結構中有很多protein-protein interacting domain，包括KIND domain、FERM domain、5個PDZ domain，於細胞中為一會與許多蛋白質交互作用之scaffold 蛋白。要了解FAP-1在肝臟疾病扮演的功能性角色，我們的策略是在肝細胞中尋找會與FAP-1有交互作用的蛋白質。本實驗室先前利用yeast two hybrid system在liver cDNA library以FAP-1的N’端為餌，找到一個新的FAP-1 associated protein，Keratin 18 (K18)，目前已知K18會與Keratin 8 (K8)形成非共價結合的heterodimer，共同組成肝細胞中主要的intermediate filaments (IFs)。 | zh_TW |
| dc.description.abstract | Fas-associated phosphates-1 (FAP-1) is a member of protein tyrosine phosphatases. According to our previous positional cloning studies, FAP-1 might serve as a potential candidate tumor suppressor gene at chromosome 4q21-23. But its function role in hepatocarcinogenesis still remains unknown.
FAP-1 contains several protein-protein interacting domains, including KIND domain, FERM domain, five PDZ domains, and thus might function as a scaffold protein. Therefore, aiming to study the functional role of FAP-1 in liver diseases, we took the approach by searching for its novel interacting protein in hepatocytes. Aided by yeast two hybrid screening of liver cDNA library, we have previously identified that Keratin 18 (K18) can interact with the N’ terminal domain of FAP-1. K18 forms the obligate non-covalent heterodimer together with its partner Keratin 8 (K8), which constitutes as the major component of the intermediate filaments (IFs) of hepatocytes. To investigate the functional effect of FAP-1 on K8/K18 IFs, the specific objectives of this study contain (1) the effect of FAP-1 on K8/K18 protein expression and specific post translational modifications (PTM), mainly focused on phosphorylation and ubiquitination; (2) the molecular mechanism underlying how FAP-1 regulates K8/K18 IFs; (3) the functional effect of FAP-1 on the structure of K8/K18 IFs. We took approach to knockdown the FAP-1 in PLC5 cells by lenti-si-RNA and then evaluate the resulting effect on the expression and PTMs of K8/K18 (loss of function approach). We found that FAP-1 knockdown can increase the protein level of K8/K18, but no significant effect on K8/K18 phosphorylation was identified. The results from quantitative PCR did not find obvious RNA changes in accordance with the changes of protein level, suggesting that FAP-1 regulates the protein level of K8/K18 might not only occur at the RNA level. Another line of evidence comes from the system we established in 293T cells, which express high level of endogenous FAP-1. By co-transfecting of K8 and K18 expression constructs into 293T cells, the K8/K18 IFs can be artificially estalished. Knockdown of FAP-1 in 293T cells caused dramatic enhance of K8/K18 protein expression level. Again, the results of quantitative PCR also supports that the effect on K8/K18 proteins might not only occur at RNA level. To further address the molecular mechanisms underlying FAP-1 affects the protein level of K8/K18, we focused on its influence on the stability of K8/K18 proteins. The results both from cyclohexamide and MG132 treatments suggested that FAP-1 might affect the protein level through regulating their protein stability. Finally, to investigate the functional effect of FAP-1 on K8/K18 IFs, FAP-1 was transfected into Huh-7 cells, which did not express FAP-1, for its effect on the K8/K18 IFs. The preliminary results showed that overexpression of FAP-1 can change the structure of K8/K18 IFs, leading to peri-nuclear aggregations, which seems to be dependent on its phosphatase activity. The results of current study supported the functional effect of FAP-1 on the protein level of K8/K18 and further suggested its influence on their protein stability as one possible mechanism. The functional role of FAP-1, through regulating the stability of K8/K18, in liver diseases is worthy to be further investigated. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-14T16:51:59Z (GMT). No. of bitstreams: 1 ntu-97-R95445109-1.pdf: 12014193 bytes, checksum: 9c8340533fc000cbc63562506f16ec44 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 口試委員會審定書……………………………………………………………………ii
致謝……………………………………………………………………………...……iii 中文摘要…………………………………………………………..………………….iv 英文摘要……...............................................................................................................vi 序論……………………………………………………………………………………1 肝癌的危險因子…………………………………………………………………....1 FAP-1蛋白質之分子結構………………………………………………………….1 FAP-1蛋白質之生理功能………………………………………………………….2 FAP-1與肝癌發展形成的關係…………………………………………………….3 Intermediate Filament (IF) Keratin 8/18與肝臟疾病之關聯………………………4 肝細胞中Mallory body (MB)與K8/K18 IF之相關性…………………………….5 肝細胞中Keratin 8/18 Intermediate Filament所受之調控………………………..7 研究目的……………………………………………………………………………..10 材料及方法…………………………………………………………………………..12 結果…………………………………………………………………………………..21 I. 利用降低FAP-1表現量的方式探討FAP-1對於K18的影響…………………21 I-1. 於表現FAP-1的PLC5細胞中利用si-RNA降低FAP-1表現量會增加 K8以及K18蛋白質的表現量……………………………………………………21 I-2. FAP-1主要影響K8/K18的表現量而非磷酸化修飾…………….…………..22 I-3. 利用定量PCR探討FAP-1影響K8/K18是否發生在RNA level之調控…..23 I-4. 於FAP-1表現量高的293T細胞中探討FAP-1對K8及K18表現量的 影響………………………………………………………………………………...24 I-5. 利用定量PCR於293T細胞株探討FAP-1影響K8及K18蛋白質是否 發生在RNA level………………………………………………………………….24 II. 探討FAP-1影響K8/K18蛋白質表現量之分子機制………………………….25 II-1. 利用cyclohexamide抑制蛋白質生合成探討FAP-1對K18蛋白質穩 定度之影響…………………………………………………………………….......25 II-2. 利用MG132抑制proteosome活性探討FAP-1對K18蛋白質降解之 影響………………………………………………………………………………...26 III. 探討FAP-1對於K8/K18 IFs結構的影響……………………………………..26 III-1. 利用si-RNA降低PLC5細胞中FAP-1表現量觀察其對於K8/K18 IFs 結構之影響………………………………..……………………………………….27 III-2. 利用外送FAP-1表現質體到Huh-7細胞中觀察其對K8/K18 IFs結構 之影響……………………………………………………………………………...27 結果討論……………………………………………………………………………..29 參考文獻……………………………………………………………………………..34 圖附錄……………………………………………………………………………..…43 | |
| dc.language.iso | zh-TW | |
| dc.subject | 去磷酸 | zh_TW |
| dc.subject | 角質蛋白 | zh_TW |
| dc.subject | 中間絲 | zh_TW |
| dc.subject | intermediate filaments | en |
| dc.subject | FAP-1 | en |
| dc.subject | Keratin-8 | en |
| dc.subject | Keratin-18 | en |
| dc.title | 探討FAP-1去磷酸酶基因對於中間絲角質蛋白Keratin-8與Keratin-18的功能性影響 | zh_TW |
| dc.title | The Functional Effect of Fas-Associated Phosphatase-1 (FAP-1) on Keratin 8/18 Intermediate Filaments | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳培哲,周祖述 | |
| dc.subject.keyword | 去磷酸,中間絲,角質蛋白, | zh_TW |
| dc.subject.keyword | FAP-1,Keratin-8,Keratin-18,intermediate filaments, | en |
| dc.relation.page | 57 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-97-1.pdf 未授權公開取用 | 11.73 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。