請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53601完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳光超(Guang-Ghao Chen) | |
| dc.contributor.author | YUEH-LING PAI | en |
| dc.contributor.author | 白玥伶 | zh_TW |
| dc.date.accessioned | 2021-06-16T02:26:13Z | - |
| dc.date.available | 2020-08-31 | |
| dc.date.copyright | 2015-08-31 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-05 | |
| dc.identifier.citation | Amerik, A.Y., and Hochstrasser, M. (2004). Mechanism and function of deubiquitinating enzymes. Biochimica et biophysica acta 1695, 189-207. Bingol, B., Tea, J.S., Phu, L., Reichelt, M., Bakalarski, C.E., Song, Q., Foreman, O., Kirkpatrick, D.S., and Sheng, M. (2014). The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 510, 370-375. Chen, X., Zhang, B., and Fischer, J.A. (2002). A specific protein substrate for a deubiquitinating enzyme: Liquid facets is the substrate of Fat facets. Genes development 16, 289-294. Choi, A.M., Ryter, S.W., and Levine, B. (2013). Autophagy in human health and disease. The New England journal of medicine 368, 1845-1846. Clague, M.J., and Urbe, S. (2010). Ubiquitin: same molecule, different degradation pathways. Cell 143, 682-685. Du, Y., Yang, D., Li, L., Luo, G., Li, T., Fan, X., Wang, Q., Zhang, X., Wang, Y., and Le, W. (2009). An insight into the mechanistic role of p53-mediated autophagy induction in response to proteasomal inhibition-induced neurotoxicity. Autophagy 5, 663-675. Glick, D., Barth, S., and Macleod, K.F. (2010). Autophagy: cellular and molecular mechanisms. The Journal of pathology 221, 3-12. Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006). Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889. He, C., and Klionsky, D.J. (2009). Regulation mechanisms and signaling pathways of autophagy. Annual review of genetics 43, 67-93. Herrmann, J., Lerman, L.O., and Lerman, A. (2007). Ubiquitin and ubiquitin-like proteins in protein regulation. Circulation research 100, 1276-1291. Hershko, A., and Ciechanover, A. (1998). The ubiquitin system. Annual review of biochemistry 67, 425-479. Jiao, H., Su, G.Q., Dong, W., Zhang, L., Xie, W., Yao, L.M., Chen, P., Wang, Z.X., Liou, Y.C., and You, H. (2015). Chaperone-like protein p32 regulates ULK1 stability and autophagy. Cell death and differentiation. Jung, C.H., Ro, S.H., Cao, J., Otto, N.M., and Kim, D.H. (2010). mTOR regulation of autophagy. FEBS letters 584, 1287-1295. Katsiarimpa, A., Kalinowska, K., Anzenberger, F., Weis, C., Ostertag, M., Tsutsumi, C., Schwechheimer, C., Brunner, F., Huckelhoven, R., and Isono, E. (2013). The deubiquitinating enzyme AMSH1 and the ESCRT-III subunit VPS2.1 are required for autophagic degradation in Arabidopsis. The Plant cell 25, 2236-2252. Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884. Korolchuk, V.I., Menzies, F.M., and Rubinsztein, D.C. (2010). Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems. FEBS letters 584, 1393-1398. Kovacs, L., Nagy, O., Pal, M., Udvardy, A., Popescu, O., and Deak, P. (2015). Role of the deubiquitylating enzyme DmUsp5 in coupling ubiquitin equilibrium to development and apoptosis in Drosophila melanogaster. PloS one 10, e0120875. Kuang, E., Okumura, C.Y., Sheffy-Levin, S., Varsano, T., Shu, V.C., Qi, J., Niesman, I.R., Yang, H.J., Lopez-Otin, C., Yang, W.Y., et al. (2012). Regulation of ATG4B stability by RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection. PLoS genetics 8, e1003007. Kuang, E., Qi, J., and Ronai, Z. (2013). Emerging roles of E3 ubiquitin ligases in autophagy. Trends in biochemical sciences 38, 453-460. Levine, B., and Klionsky, D.J. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Developmental cell 6, 463-477. Lilienbaum, A. (2013). Relationship between the proteasomal system and autophagy. International journal of biochemistry and molecular biology 4, 1-26. Low, P., Varga, A., Pircs, K., Nagy, P., Szatmari, Z., Sass, M., and Juhasz, G. (2013). Impaired proteasomal degradation enhances autophagy via hypoxia signaling in Drosophila. BMC cell biology 14, 29. Maiuri, M.C., Zalckvar, E., Kimchi, A., and Kroemer, G. (2007). Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature reviews Molecular cell biology 8, 741-752. McEwan, D.G., and Dikic, I. (2011). The Three Musketeers of Autophagy: phosphorylation, ubiquitylation and acetylation. Trends in cell biology 21, 195-201. Mesquita, F.S., Thomas, M., Sachse, M., Santos, A.J., Figueira, R., and Holden, D.W. (2012). The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. PLoS pathogens 8, e1002743. Mizuno, E., Kobayashi, K., Yamamoto, A., Kitamura, N., and Komada, M. (2006). A deubiquitinating enzyme UBPY regulates the level of protein ubiquitination on endosomes. Traffic 7, 1017-1031. Mizushima, N. (2007). Autophagy: process and function. Genes development 21, 2861-2873. Mizushima, N., Levine, B., Cuervo, A.M., and Klionsky, D.J. (2008). Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075. Nazio, F., Strappazzon, F., Antonioli, M., Bielli, P., Cianfanelli, V., Bordi, M., Gretzmeier, C., Dengjel, J., Piacentini, M., Fimia, G.M., et al. (2013). mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nature cell biology 15, 406-416. Nijman, S.M., Luna-Vargas, M.P., Velds, A., Brummelkamp, T.R., Dirac, A.M., Sixma, T.K., and Bernards, R. (2005). A genomic and functional inventory of deubiquitinating enzymes. Cell 123, 773-786. Oliveira, A.M., Hsi, B.L., Weremowicz, S., Rosenberg, A.E., Dal Cin, P., Joseph, N., Bridge, J.A., Perez-Atayde, A.R., and Fletcher, J.A. (2004). USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer research 64, 1920-1923. Pandey, U.B., Nie, Z., Batlevi, Y., McCray, B.A., Ritson, G.P., Nedelsky, N.B., Schwartz, S.L., DiProspero, N.A., Knight, M.A., Schuldiner, O., et al. (2007). HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859-863. Pickart, C.M., and Eddins, M.J. (2004). Ubiquitin: structures, functions, mechanisms. Biochimica et biophysica acta 1695, 55-72. Platta, H.W., Abrahamsen, H., Thoresen, S.B., and Stenmark, H. (2012). Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1. The Biochemical journal 441, 399-406. Poeck, B., Fischer, S., Gunning, D., Zipursky, S.L., and Salecker, I. (2001). Glial cells mediate target layer selection of retinal axons in the developing visual system of Drosophila. Neuron 29, 99-113. Sarraf, S.A., Raman, M., Guarani-Pereira, V., Sowa, M.E., Huttlin, E.L., Gygi, S.P., and Harper, J.W. (2013). Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496, 372-376. Schnell, J.D., and Hicke, L. (2003). Non-traditional functions of ubiquitin and ubiquitin-binding proteins. The Journal of biological chemistry 278, 35857-35860. Seiberlich, V., Borchert, J., Zhukareva, V., and Richter-Landsberg, C. (2013). Inhibition of protein deubiquitination by PR-619 activates the autophagic pathway in OLN-t40 oligodendroglial cells. Cell biochemistry and biophysics 67, 149-160. Shi, C.S., and Kehrl, J.H. (2010). TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Science signaling 3, ra42. Singhal, S., Taylor, M.C., and Baker, R.T. (2008). Deubiquitylating enzymes and disease. BMC biochemistry 9 Suppl 1, S3. Taillebourg, E., Gregoire, I., Viargues, P., Jacomin, A.C., Thevenon, D., Faure, M., and Fauvarque, M.O. (2012). The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins. Autophagy 8, 767-779. Tang, H.W., Wang, Y.B., Wang, S.L., Wu, M.H., Lin, S.Y., and Chen, G.C. (2011). Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy. The EMBO journal 30, 636-651. Todi, S.V., and Paulson, H.L. (2011). Balancing act: deubiquitinating enzymes in the nervous system. Trends in neurosciences 34, 370-382. Tooze, S.A., and Yoshimori, T. (2010). The origin of the autophagosomal membrane. Nature cell biology 12, 831-835. Tsou, W.L., Sheedlo, M.J., Morrow, M.E., Blount, J.R., McGregor, K.M., Das, C., and Todi, S.V. (2012). Systematic analysis of the physiological importance of deubiquitinating enzymes. PloS one 7, e43112. Varshavsky, A. (2006). The early history of the ubiquitin field. Protein science : a publication of the Protein Society 15, 647-654. Wang, C.H., Chen, G.C., and Chien, C.T. (2014). The deubiquitinase Leon/USP5 regulates ubiquitin homeostasis during Drosophila development. Biochemical and biophysical research communications 452, 369-375. Wong, E., and Cuervo, A.M. (2010). Integration of clearance mechanisms: the proteasome and autophagy. Cold Spring Harbor perspectives in biology 2, a006734. Yang, C.S., Sinenko, S.A., Thomenius, M.J., Robeson, A.C., Freel, C.D., Horn, S.R., and Kornbluth, S. (2014). The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis. Cell death and differentiation 21, 604-611. Yang, Z.F., and Klionsky, D.J. (2009). An Overview of the Molecular Mechanism of Autophagy. Curr Top Microbiol 335, 1-32. Ye, Y., and Rape, M. (2009). Building ubiquitin chains: E2 enzymes at work. Nature reviews Molecular cell biology 10, 755-764. Yeh, Y.Y., Wrasman, K., and Herman, P.K. (2010). Autophosphorylation within the Atg1 activation loop is required for both kinase activity and the induction of autophagy in Saccharomyces cerevisiae. Genetics 185, 871-882. Yorimitsu, T., and Klionsky, D.J. (2005). Autophagy: molecular machinery for self-eating. Cell death and differentiation 12 Suppl 2, 1542-1552. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53601 | - |
| dc.description.abstract | 細胞自噬是細胞遇到惡劣環境時會啟動的一種分解性機制，利用數種的ATG蛋白質形成雙層膜構造分解不需要或受破壞的胞器，用以維持細胞恆定。泛素化作用為被用來調控要被代謝物質的重要機制，部分泛素連接酶 (E3 ligase)如Traf6和Parkin被發現與細胞自噬有關，而它的逆反應去泛素化也扮演重要的角色。在人體中的去泛素酶 (deubiquitinating enzyme)有超過90種，根據其催化域可分為5大類: USP, UCH, MJD, OUT,JAMM。過去許多報導發現去泛素酶會參與調控細胞自噬，像是USP36在果蠅中會調控選擇性自胞自噬的活化，USP30和Parkin互為結抗調控粒線體自噬。此外，我們發現果蠅中的Leon被抑制後會有細胞自噬體的累積，同時細胞自噬的受質P62也有累積的現象，另外用同時帶有紅色和綠色螢光的Atg8a也發現在Leon抑制的情況下有紅色和同時帶有紅色和綠色的Atg8a累積，說明Leon可能參與調控細胞自噬。我們將進一部探討Leon如何調控細胞自噬的分子機制。 | zh_TW |
| dc.description.abstract | Autophagy is a catabolic process for cell survival under stress conditions. Autophagy related proteins (Atgs) regulate autophagosome formation to degrade damaged organelles or aggregate proteins for maintaining cellular homeostasis. Ubiquitination is an important mechanism to modulate protein degradation. Several E3 ligases such as Traf6 and Parkin have been found to be involved in autophagy. Because ubiquitination is reversible, deubiquitination may play an important role in autophagy regulation. There are over 90 deubiquitinating enzyme (DUBs) in the human. According to their catalytic domain, DUBs can be divided to five classes: USP, UCH, MJD, OUT, JAMM. Previous studies showed that several DUBs involve in autophagy regulation. For example, USP36 regulates activity of selective autophagy.USP30 antagonizes mitophagy driven by the ubiquitin ligase Parkin. Here, we found that knockdown of the Drosophila DUB, Leon, causes autophagic structure and p62 accumulation. Moreover, Leon genetically and biochemically interacts with autophagy related protein. The molecular function of Leon in autophagy is further characterized. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T02:26:13Z (GMT). No. of bitstreams: 1 ntu-104-R02b46016-1.pdf: 2066107 bytes, checksum: ee942b6bf1af59c7649e54be885cec11 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………………………………….I 致謝…………………………………………………………………………...............II 中文摘要……………………………………………………………………………...1 英文摘要……………………………………………………………………………...2 Introduction…………………………………………………………………………..3 1. Overview of autophagy............................................................................................3 2. Mechanism of autophagy………………………………………………………….4 3. Ubiquitination……………………………………………………………………...6 4. Interplay of autophagy and proteasome degradation system……………………...7 5. Autophagic regulation by ubiquitination…………………………………………..8 6. Deubiquitination by DUBs………………………………………………………...9 7. Autophagic regulation by DUBs…………………………………………………11 Material and methods………………………………………………………………13 1. fly stocks…………………………………………………………………………..13 2. Condition of feed and starvation………..…...…………………………………….14 3. Immunofluorescence………………………………………………………………14 4. Cell culture and transfection………………………………………………………14. 5. Plasmid and Primer………………………………………………………………..15 6. Antibodies and reagents…………………………………………………………...16 7. Immunoprecipitation………………………………………………………………17 8. Western blot……………………………………………………………………….17 9. GST pull down…………………………………………………………………….18 Result…………………………………………………...……………………………19 1. Leon is involved in autophagic regulation……………….………………………19 2. Atg8a puncta represent autophagic structures in Leon knockdown cells…….….19 3. Leon regulates autophagic flux……………………….………………………….20 4. Accumulation of p62 and ubiquitinated proteins in Leon knockdown cells……..20 5. Genetic interactions between Leon, ubiquitin and Atg protein…………..……....21 6. Leon interacts with Atg protein through two ubiquitin-associated domains and a histidine box…………….………………………………………………………..23 7. Leon doesn’t affect ubiquitination of Atg protein…………………………...…...23 Discussion……………………………………………………………………………26 Reference…………………………………………………………………………….29 Figure………………………………………………………………………………...33 | |
| dc.language.iso | en | |
| dc.subject | 泛素化 | zh_TW |
| dc.subject | 去泛素化 | zh_TW |
| dc.subject | 去泛素? | zh_TW |
| dc.subject | Leon | zh_TW |
| dc.subject | 自胞自噬 | zh_TW |
| dc.subject | DUB | en |
| dc.subject | deubiquitination | en |
| dc.subject | ubiquitination | en |
| dc.subject | autophagy | en |
| dc.subject | Leon | en |
| dc.title | 果蠅去泛素酶Leon調控細胞自噬之研究 | zh_TW |
| dc.title | The role of Drosophila deubiquitinating enzyme Leon in autophagy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳宏文(Hung-wen Chen),姚季光(Chi-Kuang Yao) | |
| dc.subject.keyword | 去泛素化,去泛素?,Leon,自胞自噬,泛素化, | zh_TW |
| dc.subject.keyword | deubiquitination,DUB,Leon,autophagy,ubiquitination, | en |
| dc.relation.page | 44 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-05 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf 未授權公開取用 | 2.02 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。