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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 顏伯勳 | |
dc.contributor.author | Yu-Wei Lin | en |
dc.contributor.author | 林裕緯 | zh_TW |
dc.date.accessioned | 2021-06-07T18:06:15Z | - |
dc.date.copyright | 2012-09-19 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-24 | |
dc.identifier.citation | 1. Casanova JL, Abel L: Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol 2002, 20:581-620.
2. Casanova JL, Schurr E, Abel L, Skamene E: Forward genetics of infectious diseases: immunological impact. Trends Immunol 2002, 23(10):469-472. 3. Pan H, Yan BS, Rojas M, Shebzukhov YV, Zhou H, Kobzik L, Higgins DE, Daly MJ, Bloom BR, Kramnik I: Ipr1 gene mediates innate immunity to tuberculosis. Nature 2005, 434(7034):767-772. 4. Bloch DB, Nakajima A, Gulick T, Chiche JD, Orth D, de La Monte SM, Bloch KD: Sp110 localizes to the PML-Sp100 nuclear body and may function as a nuclear hormone receptor transcriptional coactivator. Mol Cell Biol 2000, 20(16):6138-6146. 5. Watashi K, Hijikata M, Tagawa A, Doi T, Marusawa H, Shimotohno K: Modulation of retinoid signaling by a cytoplasmic viral protein via sequestration of Sp110b, a potent transcriptional corepressor of retinoic acid receptor, from the nucleus. Mol Cell Biol 2003, 23(21):7498-7509. 6. Tosh K, Campbell SJ, Fielding K, Sillah J, Bah B, Gustafson P, Manneh K, Lisse I, Sirugo G, Bennett S et al: Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa. Proc Natl Acad Sci U S A 2006, 103(27):10364-10368. 7. Liang L, Zhao YL, Yue J, Liu JF, Han M, Wang H, Xiao H: Association of SP110 gene polymorphisms with susceptibility to tuberculosis in a Chinese population. Infect Genet Evol 2011, 11(5):934-939. 8. Harding CV, Boom WH: Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat Rev Microbiol 2010, 8(4):296-307. 9. Jo EK, Yang CS, Choi CH, Harding CV: Intracellular signalling cascades regulating innate immune responses to Mycobacteria: branching out from Toll-like receptors. Cell Microbiol 2007, 9(5):1087-1098. 10. Quesniaux VJ, Nicolle DM, Torres D, Kremer L, Guerardel Y, Nigou J, Puzo G, Erard F, Ryffel B: Toll-like receptor 2 (TLR2)-dependent-positive and TLR2-independent-negative regulation of proinflammatory cytokines by mycobacterial lipomannans. J Immunol 2004, 172(7):4425-4434. 11. Ishikawa E, Ishikawa T, Morita YS, Toyonaga K, Yamada H, Takeuchi O, Kinoshita T, Akira S, Yoshikai Y, Yamasaki S: Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 2009, 206(13):2879-2888. 12. Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, Agger EM, Stenger S, Andersen P, Ruland J et al: Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 2010, 184(6):2756-2760. 13. Franchi L, Park JH, Shaw MH, Marina-Garcia N, Chen G, Kim YG, Nunez G: Intracellular NOD-like receptors in innate immunity, infection and disease. Cell Microbiol 2008, 10(1):1-8. 14. Bonizzi G, Karin M: The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004, 25(6):280-288. 15. Karin M, Greten FR: NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005, 5(10):749-759. 16. Shih VF, Tsui R, Caldwell A, Hoffmann A: A single NFkappaB system for both canonical and non-canonical signaling. Cell Res 2011, 21(1):86-102. 17. Vallabhapurapu S, Karin M: Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 2009, 27:693-733. 18. Oeckinghaus A, Hayden MS, Ghosh S: Crosstalk in NF-kappaB signaling pathways. Nat Immunol 2011, 12(8):695-708. 19. Fujii Y, Shimizu T, Kusumoto M, Kyogoku Y, Taniguchi T, Hakoshima T: Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. EMBO J 1999, 18(18):5028-5041. 20. Schuhmann KM, Pfaller CK, Conzelmann KK: The measles virus V protein binds to p65 (RelA) to suppress NF-kappaB activity. J Virol 2011, 85(7):3162-3171. 21. Ciechanover A, Gonen H, Bercovich B, Cohen S, Fajerman I, Israel A, Mercurio F, Kahana C, Schwartz AL, Iwai K et al: Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105. Biochimie 2001, 83(3-4):341-349. 22. Moorthy AK, Savinova OV, Ho JQ, Wang VY, Vu D, Ghosh G: The 20S proteasome processes NF-kappaB1 p105 into p50 in a translation-independent manner. EMBO J 2006, 25(9):1945-1956. 23. Siggers T, Chang AB, Teixeira A, Wong D, Williams KJ, Ahmed B, Ragoussis J, Udalova IA, Smale ST, Bulyk ML: Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-kappaB family DNA binding. Nat Immunol 2012, 13(1):95-102. 24. Wang J, Wang X, Hussain S, Zheng Y, Sanjabi S, Ouaaz F, Beg AA: Distinct roles of different NF-kappa B subunits in regulating inflammatory and T cell stimulatory gene expression in dendritic cells. J Immunol 2007, 178(11):6777-6788. 25. Ilmarinen T, Eskelin P, Halonen M, Ruppell T, Kilpikari R, Torres GD, Kangas H, Ulmanen I: Functional analysis of SAND mutations in AIRE supports dominant inheritance of the G228W mutation. Hum Mutat 2005, 26(4):322-331. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16238 | - |
dc.description.abstract | 肺結核 (Tuberculosis) 係由結核分枝桿菌 (Mycobacterium tuberculosis) 所引起,目前是世界上最嚴重的公共衛生問題之一。根據先前文獻的證據顯示肺結核的感染輕重與宿主的基因可能有很大的關係。經過努力找尋,近年來科學家們發現在小鼠模式上找到 Ipr1 (intracellular pathogen resistance 1) 基因,其可能參與調控宿主先天免疫反應來幫助對抗結核分枝桿菌。而在人類身上也找到和 Ipr1蛋白具同源性的SP110 蛋白,其是核質體 (nuclear bodies) 組成成分之一,亦被報導參與細胞轉錄調控。SP110 主要的異構體有 SP110a、SP110b 及 SP110c。NF-κB 訊息傳導路徑主要是活化免疫反應的相關基因,在免疫反應中是至關重要的。所以我們想研究 SP110 是否會參與 NF-κB 的轉錄調控。NF-κB 轉錄因子家族總共有五個成員,分別是 RelA (p65)、RelB、c-Rel、NF-κB 1 (p105/p50) 及NF-κB 2 (p100/p52),兩個成員間皆可以形成偶合體 (dimer)。我們觀察到大量表現 SP110a、SP110b 及 SP110c會負向調控 NF-κB 的轉錄活性,即使是共同大量表現 RelA 的情況下亦有輕微負向調控。另外,我們的資料顯示,SP110 蛋白的C端片段可能會幫助 RelA 形成homodimer 而提高轉錄活性。然而,在 NF-κB 訊息傳導路徑引發發炎反應最主要的轉錄複合體 RelA-p50 heterodimer大量表現情況下,SP110 並沒有對該複合體有很明顯的負向調控。綜合以上,SP110 會負向調控以RelA homodimer為主的轉錄活性,而在 RelA-p50 heterodimer 則沒有明顯的負向調控。 | zh_TW |
dc.description.abstract | Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the most serious infectious diseases in the world. It is evident that host genetic factors may control the disease outcome of the infection. Previous studies have identified Ipr1 (intracellular pathogen resistance 1) gene, which locates on mouse chromosome 1, as a genetic factor regulating the host innate immunity against Mtb infection. Expression of the Ipr1 gene limited Mtb multiplication and facilitated apoptotic cell death of the Mtb-infected macrophages. The closest homologue of mouse Ipr1 protein is human SP110 protein, which is a component of nuclear bodies. The SP110 protein forms at least three isoforms, SP110a, SP110b, and SP110c, and may be involved in the regulation of cell division, cell death and immune system. The NF-κB transcription factor is a protein complex controlling the transcription of many genes that play a key role in regulating the immune response to infection. NF-κB represents homo- and heterodimers of five different family members: RelA (p65), RelB, c-Rel, p50/p105 (NF-κB 1), and p52/p100 (NF-κB 2). We observed that the overexpression of SP110a, SP110b, and SP110c down-regulated the transcriptional activity mediated by NF-κB and that co-overexpressed RelA with three SP110 isoforms also did it slightly. Furthermore, our data showed that the transcriptional activity of RelA homodimer was up-regulated through interacting with the C-terminal fragments of SP110 protein. But there seemed to be very limited effect of SP110 on down-regulating RelA-p50 heterodimer which is the major NF-κB complex controlling the inflammatory response. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:06:15Z (GMT). No. of bitstreams: 1 ntu-101-R99442032-1.pdf: 842990 bytes, checksum: ae07a53b8ce46908456276c70071f444 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii ABSTRACT iii 目錄 iv 圖列表 vii 表格列表 viii Chapter 1 前言 1 1.1 肺結核與個體基因多型性 1 1.2 SP110 核蛋白 1 1.3 結核分枝桿菌與宿主免疫反應 2 1.4 NF-κB 訊息傳導路徑 3 1.5 SP110 與 NF-κB 訊息傳導路徑 5 Chapter 2 材料與方法 6 2.1 材料 6 2.2 方法 9 2.2.1 JM109 勝任細胞之製備 9 2.2.2 質體建構 9 2.2.3 質體 DNA 之抽取製備 10 2.2.4 細胞培養 11 2.2.5 細胞轉染 11 2.2.6 報導基因試驗 12 2.2.7 細胞溶裂 12 2.2.8 蛋白定量 12 2.2.9 共同免疫沉澱法 13 2.2.10 蛋白質電泳與西方點墨轉漬法 13 Chapter 3 結果 15 3.1 質體建構與雙冷光報導基因試驗 15 3.2 SP110 大量表現時NF-κB 活性之報導基因試驗 15 3.3 SP110 大量表現對 RelA活性之影響 16 3.4 SP110 與 RelA 之共同免疫沉澱反應 16 3.5 不同SP110 片段大量表現對 RelA活性之影響 17 3.6 不同SP110 片段與 RelA之共同免疫沉澱反應 17 3.7 NF-κB 1 (p50) 之製備 18 3.8 SP110 大量表現對 RelA-p50活性之影響 19 3.9 SP110 大量表現結合 TNFα誘導作用對 RelA-p50活性之影響 19 Chapter 4 討論 20 4.1 SP110負向調控NF-κB的轉錄活性 20 4.2 SP110和RelA之間的交互作用 20 4.3 SP110的 C 端片段與SP110對NF-κB 活性的功能大相逕庭 21 4.4 SP110無法有效負向調控主要的發炎反應轉錄複合體RelA-p50 22 4.5 結語 23 Chapter 5 圖表 24 Chapter 6 表格 36 Chapter 7 參考文獻 38 | |
dc.language.iso | zh-TW | |
dc.title | SP110 與轉錄因子 NF-κB 交互作用之探討 | zh_TW |
dc.title | Characterization of Interaction of SP110 with Transcription Factor NF-κB | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳美齡,俞松良 | |
dc.subject.keyword | 核蛋白,轉錄因子, | zh_TW |
dc.subject.keyword | nuclear protein SP110,transcription factor NF-κB,Rel A, | en |
dc.relation.page | 41 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-07-24 | |
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 |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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