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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 胡孟君 | |
| dc.contributor.author | Min-Ju Hsu | en |
| dc.contributor.author | 許閔茹 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:48:34Z | - |
| dc.date.available | 2018-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-12 | |
| dc.identifier.citation | 參考文獻
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BROWN, A. Y. OKAMOTO and B. SHAN, 1999 CPF: An Orphan Nuclear Receptor That Regulates Liver-Specific Expression of the Human Cholesterol 7α -Hydroxylase Gene. P Natl Acad Sci USA 96: 6660-6665. OHKI, I., N. SHIMOTAKE, N. FUJITA, J.-G. JEE, T. IKEGAMI et al., 2001 Solution Structure of the Methyl-CpG Binding Domain of Human MBD1 in Complex with Methylated DNA. Cell 105: 487-497. OHNO, M., J. KOMAKINE, E. SUZUKI, M. NISHIZUKA, S. OSADA et al., 2010 Repression of the promoter activity mediated by liver receptor homolog-1 through interaction with ku proteins. Biol Pharm Bull 33: 784-791. OIWA, A., T. KAKIZAWA, T. MIYAMOTO, K. YAMASHITA, W. JIANG et al., 2007 Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1. Biochem Bioph Res Co 353: 895-901. OOSTERVEER, M. H., C. MATAKI, H. YAMAMOTO, T. HARACH, N. MOULLAN et al., 2012 LRH-1-dependent glucose sensing determines intermediary metabolism in liver. J Clin Invest 122: 2817-2826. PARE, J. F., D. MALENFANT, C. COURTEMANCHE, M. JACOB-WAGNER, S. ROY et al., 2004 The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J Biol Chem 279: 21206-21216. PARE, J. F., S. ROY, L. GALARNEAU and L. BELANGER, 2001 The mouse fetoprotein transcription factor (FTF) gene promoter is regulated by three GATA elements with tandem E box and Nkx motifs, and FTF in turn activates the Hnf3beta Hnf4alpha, and Hnf1alpha gene promoters. J Biol Chem 276: 13136-13144. PEZZI, V., R. SIRIANNI, A. CHIMENTO, M. MAGGIOLINI, S. BOURGUIBA et al., 2004 Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-1)/fetoprotein transcription factor in the rat testis: LRH-1 as a potential regulator of testicular aromatase expression. Endocrinology 145: 2186-2196. QIN, J., D. M. GAO, Q. F. JIANG, Q. ZHOU, Y. Y. KONG et al., 2004 Prospero-related homeobox (Prox1) is a corepressor of human liver receptor homolog-1 and suppresses the transcription of the cholesterol 7-alpha-hydroxylase gene. Mol Endocrinol 18: 2424-2439. RAUSA, F. M., L. GALARNEAU, L. BELANGER and R. H. COSTA, 1999 The nuclear receptor fetoprotein transcription factor is coexpressed with its target gene HNF-3beta in the developing murine liver, intestine and pancreas. Mech Develop 89: 185-188. SABLIN, E. P., I. N. KRYLOVA, R. J. FLETTERICK and H. A. INGRAHAM, 2003 Structural Basis for Ligand-Independent Activation of the Orphan Nuclear Receptor LRH-1. Mol Cell 11: 1575-1585. SCHOONJANS, K., J. S. ANNICOTTE, T. HUBY, O. A. BOTRUGNO, E. FAYARD et al., 2002 Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I. EMBO Rep 3: 1181-1187. SHIN, D. J., and T. F. 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RAINEY, 2001 Liver receptor homologue-1 is expressed in the adrenal and can regulate transcription of 11 beta-hydroxylase. J Mol Endocrinol 27: 255-258. XU, L., C. K. GLASS and M. G. ROSENFELD, 1999 Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev 9: 140-147. XU, L., Y. WEI, J. REBOUL, P. VAGLIO, T. H. SHIN et al., 2003 BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. Nature 425: 316-321. XU PING-LONG, K. Y.-Y., XIE YOU-HUA, WANG YUAN, 2003 Corepressor SMRT Specifically Represses the Transcriptional Activity of Orphan Nuclear Receptor hB1F hLRH-1. ACTA BIOCHIMICA et BIOPHYSICA SINICA. XU, P. L., Y. Q. LIU, S. F. SHAN, Y. Y. KONG, Q. ZHOU et al., 2004 Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1. Mol Endocrinol 18: 1887-1905. YAZAWA, T., Y. INAOKA, R. OKADA, T. MIZUTANI, Y. YAMAZAKI et al., 2010 PPAR-gamma coactivator-1alpha regulates progesterone production in ovarian granulosa cells with SF-1 and LRH-1. Mol Endocrinol 24: 485-496. ZHAO, Y., X. XIONG, L. JIA and Y. SUN, 2012 Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis. Cell Death Dis 3: e386. 賴財春, 2011 LRH-1 離胺酸 329 參與泛素─蛋白酶體依賴之蛋白質水解途徑. 生 理學研究所.臺灣大學. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61135 | - |
| dc.description.abstract | Liver receptor homolog-1 (LRH-1；NR5A2) 隸屬於NR5A 核受器家族，主要表現於肝臟、小腸、胰臟以及卵巢。LRH-1 對於發育、膽固醇的逆運輸、膽酸的恆定以及固醇類荷爾蒙的生成等扮演重要的角色。先前的研究指出，LRH-1 會和調控因子產生交互作用，進而調控許多下游基因的表現；然而，目前已知與 LRH-1 有交互作用的蛋白質並不多，因此我們希望藉由酵母菌雙雜交篩選，尋找與LRH-1
有交互作用的蛋白質，並且進一步探討它們調控 LRH-1 的功能。 將 LRH-1 建構至 LexA DNA binding domain (DBD) 下游，形成誘餌蛋白，針對建構於 GAL4 activation domain (AD) 的小鼠肝臟的 cDNA library 進行篩選。共得到58 種不同的蛋白質，從中挑選出7個蛋白質，分別為H3 histone, family 3B (H3f3b)、Methyl-CpG binding domain protein 1 (Mbd1)、Zinc finger protein 579 (Zfp579)、MYC-associated zinc finger protein (Maz)、Zinc finger and BTB domain containing 44 (Zbtb44)、Ring finger protein 128 (Rnf128) 和 Nuclear receptor subfamily 1 group H, member 4 (Nr1h4, FXR)。經由共同免疫沉澱法，證實這七個蛋 白質皆與 LRH-1 有交互作用。接著利用免疫螢光染色法，發現多數的蛋白質主要分佈於細胞核，與 LRH-1 的螢光表現重疊。後續經由功能性分析 (functional assay)，包括: 西方墨點法分析以及啟動子活性分析，觀察蛋白質是否會影響 LRH-1 蛋白質的表現量或是影響 LRH-1 調控啟動子的轉錄活性。 | zh_TW |
| dc.description.abstract | Liver receptor homolog-1 (LRH-1; NR5A2) is a member of the nuclear receptor NR5A subfamily. LRH-1 is predominantly found in liver, intestine, pancreas and ovary.In these tissues, LRH-1 plays a critical role in development, reverse cholesterol transport, bile-acid homeostasis and steroidogenesis. Previous studies have shown that
LRH-1 can interact with coregulators and regulate the expression of many downstream genes. However, there are only a few proteins which were known as LRH-1-interacting proteins. Therefore, we carried out a yeast two-hybrid screen to identify proteins that will interact with LRH-1 and investigate their physiological functions with LRH-1. LRH-1 was fused to the LexA DNA binding domain (DBD) as a bait, and performed screening of the mouse liver cDNA library fused to a GAL4 activation domain (AD). Eventually, we identified 58 proteins and chose 7 of them for further investigation. These proteins are H3 histone, family 3B (H3f3b), Methyl-CpG binding domain protein 1 (Mbd1), Zinc finger protein 579 (Zfp579), MYC-associated zinc finger protein (Maz), Zinc finger and BTB domain containing 44 (Zbtb44), Ring finger protein 128 (Rnf128) and Nuclear receptor subfamily 1 group H, member 4 (Nr1h4, FXR). The co-immunoprecipitation assay verified that all of the proteins interact with LRH-1. Moreover, the immunofluorence assay results demonstrate that most of the proteins are colocalized with LRH-1 in the nucleus. We further performed the functional assay, such as: Western blotting and promoter activity assay, to identify whether these proteins will affect LRH-1 protein expression or modulate the promoter activity through LRH-1. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:48:34Z (GMT). No. of bitstreams: 1 ntu-102-R00441011-1.pdf: 1607810 bytes, checksum: 7b87ab923ad6930b38426842b0096e27 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 致謝 .................................................................................................................................. I
中文摘要 ........................................................................................................................ III Abstract ........................................................................................................................... IV 圖次 ............................................................................................................................... VII 表次 .............................................................................................................................. VIII 第一章 序論 .................................................................................................................... 1 一、LRH-1 簡介 ..................................................................................................... 1 1. LRH-1 之蛋白質結構 ................................................................................. 1 2. LRH-1 之生理性功能 ................................................................................. 2 3. LRH-1 之輔調控因子 .................................................................................. 3 二、酵母菌雙雜交系統 (Yeast two-hybrid system) .............................................. 6 1. 原理 ............................................................................................................. 6 2. 優點與限制 ................................................................................................. 7 三、研究目的 .......................................................................................................... 8 第二章 材料與方法 ........................................................................................................ 9 一、酵母菌株 .......................................................................................................... 9 二、酵母菌表現質體 .............................................................................................. 9 三、培養基與試劑的配製 .................................................................................... 10 四、轉型質體至酵母菌 ......................................................................................... 11 五、酵母菌中誘餌蛋白質表現分析 .................................................................... 12 六、西方墨點法分析 ............................................................................................ 13 七、組胺酸 (Histidine) 與 X-gal 測試 .............................................................. 14 八、酵母菌雙雜交篩選 ........................................................................................ 14 九、X-gal 陽性菌落 cDNA 之確認 .................................................................... 15 十、第二次 X-gal 測試 ....................................................................................... 16 十一、細胞培養 .................................................................................................... 17 十二、細胞表現質體 ............................................................................................ 17 十三、候選蛋白質質體建構 ................................................................................ 18 十四、暫時性轉染法 (Transient transfection) ..................................................... 23 十五、冷光酶活性分析 (Luciferase assay) ......................................................... 24 十六、細胞蛋白質表現分析 ................................................................................ 24 十七、共同免疫沉澱法 (Co-immunoprecipitation) ............................................ 25 十八、免疫螢光染色法 (Immunofluorence) ....................................................... 26 十九、統計分析 .................................................................................................... 27 第三章 結果 .................................................................................................................. 28 一、酵母菌表現誘餌蛋白質 ................................................................................ 28 二、誘餌蛋白質背景活性測試 ............................................................................ 28 三、酵母菌雙雜交篩選 ........................................................................................ 30 四、證明候選蛋白質與 LRH-1 之間有交互作用的關係 ................................. 31 五、候選蛋白質與 LRH-1 的功能性分析 ......................................................... 31 第四章 討論 .................................................................................................................. 35 參考文獻 ........................................................................................................................ 39 | |
| dc.language.iso | zh-TW | |
| dc.subject | 啟動子活性分析 | zh_TW |
| dc.subject | LRH-1 | zh_TW |
| dc.subject | 西方墨點法分析 | zh_TW |
| dc.subject | 免疫螢光染色法 | zh_TW |
| dc.subject | 共同免疫沉澱法 | zh_TW |
| dc.subject | 酵母菌雙雜交篩選 | zh_TW |
| dc.subject | promoter activity assay | en |
| dc.subject | yeast two-hybrid screen | en |
| dc.subject | co-immunoprecipitation assay | en |
| dc.subject | immunofluorence assay | en |
| dc.subject | Western blotting | en |
| dc.subject | LRH-1 | en |
| dc.title | 利用酵母菌雙雜交技術找尋在小鼠肝中與 LRH-1
有交互作用的蛋白質 | zh_TW |
| dc.title | Application of yeast two-hybrid screen to identify
LRH-1-interacting proteins in mouse liver | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭瓊娟,繆希椿,徐立中 | |
| dc.subject.keyword | LRH-1,酵母菌雙雜交篩選,共同免疫沉澱法,免疫螢光染色法,西方墨點法分析,啟動子活性分析, | zh_TW |
| dc.subject.keyword | LRH-1,yeast two-hybrid screen,co-immunoprecipitation assay,immunofluorence assay,Western blotting,promoter activity assay, | en |
| dc.relation.page | 59 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| 顯示於系所單位： | 生理學科所 | |
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