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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 張茂山(Mau-Sun Chang) | |
dc.contributor.author | Hao-Yen Chang | en |
dc.contributor.author | 張皓衍 | zh_TW |
dc.date.accessioned | 2021-06-15T06:10:20Z | - |
dc.date.available | 2010-08-16 | |
dc.date.copyright | 2010-08-16 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-13 | |
dc.identifier.citation | Amin HM, Medeiros LJ, Ma Y, Feretzaki M, Das P, Leventaki V, Rassidakis GZ, O'Connor SL, McDonnell TJ, Lai R. (2003) Inhibition of JAK3 induces apoptosis and decreases anaplastic lymphoma kinase activity in anaplastic large cell lymphoma. Oncogene 22: 5399-5407.
Armstrong F, Duplantier MM, Trempat P, Hieblot C, Lamant L, Espinos E, Racaud-Sultan C, Allouche M, Campo E, Delsol G, Touriol C. (2004) Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells. Oncogene 23: 6071-6782. Bai RY, Dieter P, Peschel C, Morris SW, Duyster J. (1998) Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity. Mol Cell Biol 18: 6951-6961. Bai RY, Ouyang T, Miething C, Morris SW, Peschel C, Duyster J. (2000) Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway. Blood 96: 4319-4327. Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugières L, Terrier-Lacombe MJ, Haralambieva E, Pulford K, Pileri S, Morris SW, Mason DY, Delsol G. (1998) ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood 91: 2076-2084. Bowden ET, Stoica GE, Wellstein A. (2002) Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase. J Biol Chem 277: 35862-35868. Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S. (2008) Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455: 971-974. Cheung HH, Lynn Kelly N, Liston P, Korneluk RG. (2006) Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs. Exp Cell Res 312: 2347-2357. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325: 834-840. Cools J, Wlodarska I, Somers R, Mentens N, Pedeutour F, Maes B, De Wolf-Peeters C, Pauwels P, Hagemeijer A, Marynen P. (2002) Identification of Novel Fusion Partners of ALK, the Anaplastic Lymphoma Kinase, in Anaplastic Large-Cell Lymphoma and Inflammatory Myofibroblastic Tumor. Genes Chromosomes Cancer 34: 354-362. Davenport EL, Moore HE, Dunlop AS, Sharp SY, Workman P, Morgan GJ, Davies FE. (2007) Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Blood 110: 2641-2649. Degoutin J, Brunet-de Carvalho N, Cifuentes-Diaz C, Vigny M. (2009) ALK (Anaplastic Lymphoma Kinase) expression in DRG neurons and its involvement in neuron-Schwann cells interaction. Eur J Neurosci 29: 275-286. Denuc A, Marfany G. (2010) SUMO and ubiquitin paths converge. Biochem Soc Trans 38: 34-39. Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP. (2008) A quantitative atlas of mitotic phosphorylation. PNAS 105: 10762-10767. Duyster J, Bai RY, Morris SW. (2001) Translocations involving anaplastic lymphoma kinase (ALK). Oncogene 20: 5623-5637. Ferri KF, Kroemer G. (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3: E255-263. Han G, Ye M, Zhou H, Jiang X, Feng S, Jiang X, Tian R, Wan D, Zou H, Gu J. (2008) Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography. Proteomics 8: 1346-1361. Hurley SP, Clary DO, Copie V, Lefcort F. (2006) Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system. J Comp Neurol 495: 202-212. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y. (2008) Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci 24: 161-166. Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T, Mori S, Ratzkin B, Yamamoto T. (1997) Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 14: 439-449. Khoury JD, Medeiros LJ, Rassidakis GZ, Yared MA, Tsioli P, Leventaki V, Schmitt-Graeff A, Herling M, Amin HM, Lai R. (2003) Differential expression and clinical significance of tyrosine-phosphorylated STAT3 in ALK+ and ALK- anaplastic large cell lymphoma. Clin Cancer Res 9: 3692-3699. Khoury JD, Rassidakis GZ, Medeiros LJ, Amin HM, Lai R. (2004) Methylation of SHP1 gene and loss of SHP1 protein expression are frequent in systemic anaplastic large cell lymphoma. Blood 104:1580-1581. Kikuno R, Nagase T, Suyama M, Waki M, Hirosawa M, Ohara O. (2000) HUGE: a database for human large proteins identified in the Kazusa cDNA sequencing project. Nucleic Acids Res 28: 331-332. Kuo AH, Stoica GE, Riegel AT, Wellstein A. (2007) Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase. Oncogene 26: 859-869. Ladanyi M, Cavalchire G. (1996) Detection of the NPM-ALK genomic rearrangement of Ki-1 lymphoma and isolation of the involved NPM and ALK introns. Diagn Mol Pathol 5: 154-158. Lorén CE, Englund C, Grabbe C, Hallberg B, Hunter T, Palmer RH. (2003) A crucial role for the Anaplastic lymphoma kinase receptor tyrosine kinase in gut development in Drosophila melanogaster. EMBO Rep 4: 781-786. Lowe EJ, Sposto R, Perkins SL, Gross TG, Finlay J, Zwick D, Abromowitch M. (2009) Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: Final results of children's cancer group study 5941. Pediatr Blood Cancer 52: 335-339. Marzec M, Kasprzycka M, Liu X, Raghunath PN, Wlodarski P, Wasik MA. (2007) Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf. Oncogene 26: 813-821. Mathas S, Kreher S, Meaburn KJ, Jöhrens K, Lamprecht B, Assaf C, Sterry W, Kadin ME, Daibata M, Joos S, Hummel M, Stein H, Janz M, Anagnostopoulos I, Schrock E, Misteli T, Dörken B. (2009) Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma. PNAS 106: 5831-5836. Méndez J, Stillman B. (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol 20: 8602-8612. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT. (1994) Fusion of a kinase gene, ALK, to a nucleolar protein gene,NPM, in non-Hodgkin’s lymphoma. Science 263: 1281–1284. Morris SW, Xue L, Ma Z, Kinney MC. (2001) Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma. Br J Haematol 113: 275-295. Mossé YP, Wood A, Maris JM. (2009) Inhibition of ALK signaling for cancer therapy. Clin Cancer Res 15: 5609-5614. Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O. (2000) Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res 7: 273-281. Palmer RH, Vernersson E, Grabbe C, Hallberg B. (2009) Anaplastic lymphoma kinase: signalling in development and disease. Biochem J 420: 345-361. Pulford K, Lamant L, Espinos E, Jiang Q, Xue L, Turturro F, Delsol G, Morris SW. (2004) The emerging normal and disease-related roles of anaplastic lymphoma kinase. Cell Mol Life Sci 61: 2939-2953. Rassidakis GZ, Feretzaki M, Atwell C, Grammatikakis I, Lin Q, Lai R, Claret FX, Medeiros LJ, Amin HM. (2005) Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma. Blood 105: 827-829. Römisch K. (2005) Endoplasmic reticulum-associated degradation. Annu Rev Cell Dev Biol 21: 435-456. Schröder M, Kaufman RJ. (2005) ER stress and the unfolded protein response. Mutat Res 569: 29-63. Soldani S and Scovassi AI (2002) Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7: 321-328. Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H, Schwarting R, Lennert K. (1985) The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 66: 848-858. Suzuki T, Lu J, Zahed M, Kita K, Suzuki N. (2007) Reduction of GRP78 expression with siRNA activates unfolded protein response leading to apoptosis in HeLa cells. Arch Biochem Biophys 468: 1-14. Tanimoto R, Sakaguchi M, Abarzua F, Kataoka K, Kurose K, Murata H, Nasu Y, Kumon H, Huh NH. (2010) Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3. Int J Cancer 126: 1562-1569. Touriol C, Greenland C, Lamant L, Pulford K, Bernard F, Rousset T, Mason DY, Delsol G. (2000) Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like). Blood 95: 3204-3207. Wasik MA, Zhang Q, Marzec M, Kasprzycka M, Wang HY, Liu X. (2009) Anaplastic lymphoma kinase (ALK)-induced malignancies: novel mechanisms of cell transformation and potential therapeutic approaches. Semin Oncol 36: S27-35. Xu D, Perez RE, Rezaiekhaligh MH, Bourdi M, Truog WE. (2009) Knockdown of ERp57 increases BiP/GRP78 induction and protects against hyperoxia and tunicamycin-induced apoptosis. Am J Physiol Lung Cell Mol Physiol 297: L44-51. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47644 | - |
dc.description.abstract | KIAA1618/ALO17是在異生性大細胞淋巴瘤 (Anaplastic large cell lymphoma, ALCL) 病例中所發現的功能未知蛋白,由1063個胺基酸組成,在這些ALCL病例中,KIAA1618的N端 (胺基酸序列1-1008) 與異生性淋巴瘤激酶 (Anaplastic lymphoma kinase, ALK) 的C端 (胺基酸序列 1058-1620 ) 形成新的融合蛋白,根據先前的研究,融合蛋白與致癌性有密切的關係。為了研究KIAA1618的功能,將含有HA-tag KIAA1618的質體DNA轉染HEK293T細胞,利用免疫沉澱收取表現蛋白,根據銀離子染色與西方墨點法的結果,KIAA1618表現在接近170 kDa的位置,比預測大小118.43 kDa來的高。分層萃取與免疫螢光染色顯示KIAA1618主要分布於細胞質。利用In vivo ubiquitination assay,顯示在MG132 (proteasome inhibitor) 處理下,KIAA1618具有多泛素化的特性,而利用誘發內質網壓力的藥物也可以發現類似的特性。進一步,凋亡細胞偵測顯示大量表現KIAA1618的HeLa細胞對於Tunicamycin (N-glycosylation inhibitor)與Thapsigargin (Ca2+ pump inhibitor) 處理有較高的耐受性;比較在兩種藥物處理下蛋白質的表現量,結果發現在大量表現KIAA1618的HeLa細胞,Grp78的表現量和PARP-1的斷裂都有顯著降低。總結實驗結果,KIAA1618可能會增加細胞對內質網壓力的耐受性。 | zh_TW |
dc.description.abstract | KIAA1618/ALO17 is a novel protein discovered from the cases of the anaplastic large cell lymphoma (ALCL). A chimeric protein created due to a translocation of the N-terminal KIAA1618 protein (a.a. 1-1008) fused with the C-terminal truncated anaplastic lymphoma kinase (ALK, a.a. 1058-1620). According to the reported cases of ALCL, the oncogenesis is highly correlated with this chimeric protein. Nonetheless, the physiological function of KIAA1618 is still remained unclear. Using HA-tagged KIAA1618 to transfect HEK293 cells, silver-stain and Western blotting results showed that KIAA1618 migrated at approximate 170 kDa on SDS-PAGE which is much higher than an estimated 118.43 kDa from the predicted 1063 amino acids of KIAA1618 cDNA. Subcellular fraction and immunofluorescence staining revealed a predominant cytosolic distribution of KIAA1618. In vivo ubiquitination assay showed that KIAA1618 was poly-ubiquitinated with the addition of MG132, a proteasome inhibitor. A similar result was found when cells were exposed to some ER stress drugs. Moreover, apoptotic detections showed that KIAA1618 overexpressing HeLa cells were resistant to Tunicamycin and Thapsigargin treatment, an N-glycosylation inhibitor and a Ca2+ pump inhibitor, compared with control cells. Finally, a significant decrease in the expression level of Grp78 and PARP-1 cleavage was found in KIAA1618 overexpressing compared with control cells treated with Tunicamycin and Thapsigargin. Collectively, these results suggested that KIAA1618 may render cells resistance to ER stress. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:10:20Z (GMT). No. of bitstreams: 1 ntu-99-R97b46023-1.pdf: 8677729 bytes, checksum: 93bae261bbd0a10a5c747bf0fd632ade (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 中文摘要………………………………………………………………………….........i
英文摘要……………………………………………...……………………………….ii 縮寫表………………………………………………………………………………...iii 目錄………………………………………………………………………………….. .v 第一章 前言…………………………………………………………………………..1 1.1 異生性大細胞淋巴瘤(Anaplastic large cell lymphoma,ALCL)…………1 1.2 異生性淋巴瘤激酶 (Anaplastic lymphoma kinase,ALK)……………….2 1.3 ALK融合蛋白………………………………………………………………3 1.4 ALK融合蛋白的致癌性訊息傳遞…………………………………………4 1.5 KIAA1618/ALO17 (ALK lymphoma oligomerization partner on chromosome 17)…………………………………………………………………6 1.6 研究動機……………………………………………………………............7 第二章 材料與方法…………………………………………………………………..8 2.1.1 細胞株培養……………………………………………………………….8 2.1.2細胞計數…………………………………………………………………..8 2.1.3 加藥處理………………………………………………………………….8 2.2.1 細胞蛋白質萃取 (Whole cell extract)………………………………...…9 2.2.2 染色質分離 (Chromatin fractionation)…………………………………..9 2.3.1 凋亡細胞偵測:Propidium Iodide核酸染色..........................................10 2.3.2 凋亡細胞偵測:FITC-Annexin V/Propidium Iodide雙重染色................10 2.4 免疫沉澱…………………………………………………………..……..11 2.5 免疫螢光染色……………………………………………………..……..12 2.6.1 基因轉染………………………………………………………………...12 2.6.2 大量表現細胞株建立…………………………………………………...13 2.6.3 In vivo ubiquitination assay……………………………………………...13 2.7.1 SDS-PAGE膠體電泳……………………………………………………14 2.7.2 西方墨點法…………………………………………………………...…15 2.7.3 銀離子染色…………………………………………………………...…15 2.8 In gel digestion…………………...……………………………………..16 第三章 實驗結果……………………………………………………………………17 3.1 KIAA1618蛋白質的表現大小……………………………………………17 3.2 KIAA1618在細胞內的分布………………………………………………17 3.3 透過LC-MS/MS尋找KIAA1618可能的關連蛋白…………………….18 3.4 KIAA1618具有泛素化的特性…………………….....................………18 3.5 大量表現KIAA1618的HeLa細胞受到Tunicamycin與Thapsigargin處理時的反應…................................................................................................….19 3.6 大量表現KIAA1618的HeLa細胞受到Tunicamycin與Thapsigargin處理時的蛋白表現量………………....................................…………...………..20 第四章 總結與討論…………………………………………………………………22 第五章 實驗結果圖表………………………………………………………………25 附錄…………………………………………………………………………………..37 參考文獻……………………………………………………………………………..40 | |
dc.language.iso | zh-TW | |
dc.title | 異生性淋巴瘤激酶相關蛋白KIAA1618的研究 | zh_TW |
dc.title | Studies on an ALK related novel protein KIAA1618 | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張震東(Geen-Dong Chang),張世宗(Shih-Chung Chang),朱家瑩(Chia-Ying Chu) | |
dc.subject.keyword | 異生性大細胞淋巴瘤,異生性淋巴瘤激酶, | zh_TW |
dc.subject.keyword | KIAA1618,ALO17, | en |
dc.relation.page | 45 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-15 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科學研究所 | zh_TW |
顯示於系所單位: | 生化科學研究所 |
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