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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 生物化學暨分子生物學科研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/39204
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dc.contributor.advisor林榮耀
dc.contributor.authorFa-Han Leeen
dc.contributor.author李法漢zh_TW
dc.date.accessioned2021-06-13T17:24:18Z-
dc.date.available2005-01-31
dc.date.copyright2005-01-31
dc.date.issued2005
dc.date.submitted2005-01-26
dc.identifier.citation1. Pawson, T. and T. Hunter, Signal transduction and growth control in normal and cancer cells. Curr Opin Genet Dev, 1994. 4(1): p. 1-4.
2. Malumbres, M. and A. Carnero, Cell cycle deregulation: a common motif in cancer. Prog Cell Cycle Res, 2003. 5: p. 5-18.
3. Zender, L., et al., VP22-mediated intercellular transport of p53 in hepatoma cells in vitro and in vivo. Cancer Gene Ther, 2002. 9(6): p. 489-96.
4. Maruta, H., et al., G proteins, phosphoinositides, and actin-cytoskeleton in the control of cancer growth. Microsc Res Tech, 1999. 47(1): p. 61-6.
5. Hirohashi, S. and Y. Kanai, Cell adhesion system and human cancer morphogenesis. Cancer Sci, 2003. 94(7): p. 575-81.
6. Malliri, A. and J.G. Collard, Role of Rho-family proteins in cell adhesion and cancer. Curr Opin Cell Biol, 2003. 15(5): p. 583-9.
7. Rinker-Schaeffer, C.W., M.A. Chekmareva, and J.L. Mohler, The role of motility proteins and metastasis-suppressor genes in prostate cancer progression. Stem Cells, 1996. 14(5): p. 508-16.
8. Banyard, J. and B.R. Zetter, The role of cell motility in prostate cancer. Cancer Metastasis Rev, 1998. 17(4): p. 449-58.
9. Lin, M. and K.L. van Golen, Rho-regulatory proteins in breast cancer cell motility and invasion. Breast Cancer Res Treat, 2004. 84(1): p. 49-60.
10. Taniai, N., et al., Adrenal metastasis from hepatocellular carcinoma (HCC): report of 3 cases. Hepatogastroenterology, 1999. 46(28): p. 2523-8.
11. Cheng, L., et al., Risk of prostate carcinoma death in patients with lymph node metastasis. Cancer, 2001. 91(1): p. 66-73.
12. Whang-Peng, J. and Y. Chao, Clinical trials of HCC in Taiwan. Hepatogastroenterology, 1998. 45(24): p. 1937-43.
13. Tsai, C.C., et al., Large-scale sequencing analysis of the full-length cDNA library of human hepatocellular carcinoma. J Biomed Sci, 2003. 10(6 Pt 1): p. 636-43.
14. Field, J., et al., Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein. Cell, 1990. 61(2): p. 319-27.
15. Freeman, N.L., et al., An actin monomer binding activity localizes to the carboxyl-terminal half of the Saccharomyces cerevisiae cyclase-associated protein. J Biol Chem, 1995. 270(10): p. 5680-5.
16. Matviw, H., G. Yu, and D. Young, Identification of a human cDNA encoding a protein that is structurally and functionally related to the yeast adenylyl cyclase-associated CAP proteins. Mol Cell Biol, 1992. 12(11): p. 5033-40.
17. Freeman, N.L., et al., A conserved proline-rich region of the Saccharomyces cerevisiae cyclase-associated protein binds SH3 domains and modulates cytoskeletal localization. Mol Cell Biol, 1996. 16(2): p. 548-56.
18. Gieselmann, R. and K. Mann, ASP-56, a new actin sequestering protein from pig platelets with homology to CAP, an adenylate cyclase-associated protein from yeast. FEBS Lett, 1992. 298(2-3): p. 149-53.
19. Gottwald, U., et al., Identification of a cyclase-associated protein (CAP) homologue in Dictyostelium discoideum and characterization of its interaction with actin. Mol Biol Cell, 1996. 7(2): p. 261-72.
20. Freeman, N.L. and J. Field, Mammalian homolog of the yeast cyclase associated protein, CAP/Srv2p, regulates actin filament assembly. Cell Motil Cytoskeleton, 2000. 45(2): p. 106-20.
21. Moriyama, K. and I. Yahara, Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover. J Cell Sci, 2002. 115(Pt 8): p. 1591-601.
22. Bertling, E., et al., Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell, 2004. 15(5): p. 2324-34.
23. Pawlak, G. and D.M. Helfman, Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev, 2001. 11(1): p. 41-7.
24. Yu, J., et al., A cytoskeletal localizing domain in the cyclase-associated protein, CAP/Srv2p, regulates access to a distant SH3-binding site. J Biol Chem, 1999. 274(28): p. 19985-91.
25. Hotulainen, P., et al., ADF and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Non-Muscle Cells. Mol Biol Cell, 2004.
26. Bamburg, J.R., Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol, 1999. 15: p. 185-230.
27. Carlier, M.F., F. Ressad, and D. Pantaloni, Control of actin dynamics in cell motility. Role of ADF/cofilin. J Biol Chem, 1999. 274(48): p. 33827-30.
28. McGough, A., B. Pope, and A. Weeds, The ADF/cofilin family: accelerators of actin reorganization. Results Probl Cell Differ, 2001. 32: p. 135-54.
29. McGough, A., et al., Cofilin changes the twist of F-actin: implications for actin filament dynamics and cellular function. J Cell Biol, 1997. 138(4): p. 771-81.
30. Moriyama, K., K. Iida, and I. Yahara, Phosphorylation of Ser-3 of cofilin regulates its essential function on actin. Genes Cells, 1996. 1(1): p. 73-86.
31. Nebl, G., S.C. Meuer, and Y. Samstag, Dephosphorylation of serine 3 regulates nuclear translocation of cofilin. J Biol Chem, 1996. 271(42): p. 26276-80.
32. Yahara, I., et al., A role of cofilin/destrin in reorganization of actin cytoskeleton in response to stresses and cell stimuli. Cell Struct Funct, 1996. 21(5): p. 421-4.
33. Bullions, L.C. and A.J. Levine, The role of beta-catenin in cell adhesion, signal transduction, and cancer. Curr Opin Oncol, 1998. 10(1): p. 81-7.
34. Cavallaro, U. and G. Christofori, Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer, 2004. 4(2): p. 118-32.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/39204-
dc.description.abstract腺核苷環化酶結合蛋白(cyclase-associated protein)最早是在酵母菌中被發現的一個具有雙重功能的特殊蛋白,其胺基端功能區被發現和腺核苷環化酶/環腺單核苷之訊息傳遞有關,羧基端則具有一肌動球蛋白結合功能區。然而隨著演化的進行,胺基端功能區逐漸失去原有的特性,相對的羧基端功能區則具有高度的保留性。在豬和黏菌的研究則發現CAP能隔絕肌動球蛋白而造成細胞內微絲的瓦解。除了胺基端和羧基端之外,CAP的中間區段則含有兩個多重脯胺酸片段,分別為P1及P2。已知P2片段具有SH3結合能力,而P1片段的功能則屬未知。如此,CAP在高等真核細胞中應和調控微絲的形成有關,但其在細胞生理上的定位,尚不明朗。
本實驗室近年來致力於肝癌相關基因的研究。藉著高速大量的核酸定序分析,我們在一個C型肝炎肝細胞癌(HCV-infected hepatocellular carcinoma)全長cDNA基因庫中發現數個具有缺陷的cDNA,其中包含人類第一型腺核苷環化酶結合蛋白(CAP1)的缺陷突變株。序列比對分析的結果顯示,此一缺陷將造成CAP1第97個甲胺酸到第319個脯胺酸被刪除(
zh_TW
dc.description.abstractCyclase-associated protein (CAP) was first identified in yeast. Yeast CAP is a special bifunctional protein whose N-terminal domain interacts with the adenylyl cyclase, and C-terminal has a G-actin binding activity and an actin binding domain. In higher eukaryotes, CAP protein loses its ability to interact with adenylyl cyclase, while the actin binding ability is conserved during evolution. Studies in Dictyostelium discoideum and porcine CAP homologs suggested that CAP can act as an actin-squestering factor which causes F-actin depolymerization. Another important functional domain lies within the internal part of CAP, which contains two poly-proline motifs, P1 and P2. The less conserved P2 motif has been proved to be a SH3-binding domain, while the function of the highly conserved P1 motif is still not clear. Previous studies of yeast CAP have shown that the P2 motif is responsible for CAP’s cytoskeletal localization. In brief, CAP and its homologs are believed to regulate actin cytoskeleton, although the actual biological functions of CAP protein have not yet been determined.
By high-throughput sequence analysis of a human hepatocellular carcinoma (HCC) full-length cDNA library (constructed from a human hepatitis C virus infected cancer patient’s tumor and normal tissue), a deletion mutant (
en
dc.description.provenanceMade available in DSpace on 2021-06-13T17:24:18Z (GMT). No. of bitstreams: 1
ntu-94-R91442021-1.pdf: 699649 bytes, checksum: 676b427a32d313ad3c5339a3eac63a94 (MD5)
Previous issue date: 2005
en
dc.description.tableofcontentsList of Figures ii
中文摘要 1
Abstract 2-3
Introduction 4-6
Materials and Methods 7-24
Materials 7
Plasmids costruction 8-12
Plasmids maxi-preparation by ultracentrifugation 12-15
Transient transfection and protein expression 15-20
Confocal microscopy 20-22
Co-immunoprecipitation 22-24
Real-time PCR 24
Results 25-31
Discussion 32-39
References 40-43
Figures 44-49
Legends 50-53
dc.language.isoen
dc.subject肝癌zh_TW
dc.subject腺核&#33527zh_TW
dc.subject環化脢結合蛋白zh_TW
dc.subjectCAP1en
dc.subjectHCCen
dc.subjectcyclase-associated protein 1en
dc.subjectcofilinen
dc.title針對二候選肝癌基因之功能性研究zh_TW
dc.titleStudies on The Function of Two Hepatocellular Carcinoma Candidate Genes--Cyclase-associated Protein 1 and Cofilinen
dc.typeThesis
dc.date.schoolyear93-1
dc.description.degree碩士
dc.contributor.oralexamcommittee錢宗良,張明富,呂紹俊,廖大修
dc.subject.keyword腺核&#33527,環化脢結合蛋白,肝癌,zh_TW
dc.subject.keywordcofilin,CAP1,cyclase-associated protein 1,HCC,en
dc.relation.page53
dc.rights.note有償授權
dc.date.accepted2005-01-27
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept生物化學暨分子生物學研究所zh_TW
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