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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃偉邦(Wei-Pang Huang) | |
dc.contributor.author | Kung-Hsien Ho | en |
dc.contributor.author | 何恭憲 | zh_TW |
dc.date.accessioned | 2021-06-13T00:38:59Z | - |
dc.date.available | 2007-07-30 | |
dc.date.copyright | 2007-07-30 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-25 | |
dc.identifier.citation | Abeliovich, H, Dunn WA Jr, Kim J, and Klionsky DJ (2000) Dissection of autophagosome biogenesis into distinct nucleation and expansion steps. J Cell Biol. 151:1025-1034.
Abeliovich, H and Klionsky DJ (2001) Autophagy in yeast: mechanistic insights and physiological function. Microbiol Mol Biol Rev. 65:463-479. Adams, J (2003) The proteasome: structure, function, and role in the cell. Cancer Treat Rev. 1:3-9. Amar, N, Lustig G, Ichimura Y, Ohsumi Y, and Elazar Z (2006) Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy. EMBO Rep. 7: 635-642. Baba, M, Osumi M, Scott SV, Klionsky DJ, and Ohsumi Y (1997) Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome. J Cell Biol. 139:1687-1689. Barlowe, C (2000) Traffic COPs of the early secretory pathway. Traffic 1:371-377. Bernales, S, McDonald KL, and Walter P (2006) Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol. 4:e423. Bethune, J, Wieland F, and Moelleken J (2006) COPI-mediated transport. J Membr Biol. 211:65-79. Bjorkoy, G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, and Johansen T (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 171:603-614. Bonifacino, JS and Glick BS (2004) The mechanisms of vesicle budding and fusion. Cell 116:153-166. Chang, CY and Huang WP (2007) Atg19 mediates a dual interaction cargo sorting mechanism in selective autophagy. Mol Biol Cell. 18:919-929. Clark, SL Jr (1957) Cellular differentiation in the kidneys of newborn mice studies with the electron microscope. J Biophys Biochem Cytol. 3:349-362. Deretic, V, Singh S, Master S, Harris J, Roberts E, Kyei G, Davis A, de Haro S, Naylor J, Lee HH, and Vergne I (2006) Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism. Cell Microbiol. 8:719-727. Glickman, MH and Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 82:373-428. Gutierrez, MG, Master SS, Singh SB, Taylor GA, Colombo MI, and Deretic V (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753-766. Hamasaki, M, Noda T, and Ohsumi Y (2003) The early secretory pathway contributes to autophagy in yeast. Cell Struct Funct. 28:49-54. Hamai, C, Yang T, Kataoka S, Cremer PS, and Musser SM (2006) Effect of average phospholipid curvature on supported bilayer formation on glass by vesicle fusion. Biophys J. 90:1241-1248. Hara, T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885-889. Harding, TM, Morano KA, Scott SV, and Klionsky DJ (1995) Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 131:591-602. Hochstrasser, M (1996) Ubiquitin-dependent protein degradation. Annu Rev Genet. 30:405-439. Huang, WP, Scott SV, Kim J, Klionsky DJ (2000) The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem. 275:5845-5851. Huang, WP, Klionsky DJ (2002) Autophagy in yeast: a review of the molecular machinery. Cell Struct Funct. 6:409-420, Hui, SW and Sen A (1989) Effects of lipid packing on polymorphic phase behavior and membrane properties. Proc Natl Acad Sci U S A. 86:5825-5829. Hutchins, MU and Klionsky DJ (2001) Vacuolar localization of oligomeric alpha-mannosidase requires the cytoplasm to vacuole targeting and autophagy pathway components in Saccharomyces cerevisiae. J Biol Chem. 276:20491-20498. Hutchins, MU, Veenhuis M, and Klionsky DJ (1999) Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway. J Cell Sci. 112:4079-4087. Ichimura, Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, and Ohsumi Y. (2000) A ubiquitin-like system mediates protein lipidation. Nature 408:488-492. Ishihara, N, Hamasaki M, Yokota S, Suzuki K, Kamada Y, Kihara A, Yoshimori T, Noda T, and Ohsumi Y (2001) Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell. 12:3690-3702. James, P, Halladay J, and Craig EA (1996) Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast Genetic 144:1425-1436. Legesse-Miller, A, Sagiv Y, Glozman R, and Elazar Z (2000) Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes. J Biol Chem. 275:32966-32973. Le Roy, C and Wrana JL (2005) Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling. Nat Rev Mol Cell Biol. 6:112-126. Kihara, A, Noda T, Ishihara N, and Ohsumi Y (2001) Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol. 152:519-530. Kirisako, T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, Noda T, and Ohsumi Y (1999) Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 147:435-446. Kirisako, T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, Ohsumi M, Takao T, Noda T, and Ohsumi Y (2000) The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol. 151:263-276. Kim, J, Scott SV, Oda MN, and Klionsky DJ (1997) Transport of a large oligomeric protein by the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 137:609-618. Kim, J, Huang WP, and Klionsky DJ (2001a) Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 152:51-64. Kim, J, Kamada Y, Stromhaug PE, Guan J, Hefner-Gravink A, Baba M, Scott SV, Ohsumi Y, Dunn WA, and Klionsky DJ (2001b) Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole. J Cell Biol. 153:381-396. Kim, J, Huang WP, Stromhaug PE, and Klionsky DJ (2002) Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation J Biol Chem. 277:763-773. Klionsky, DJ (2005) The molecular machinery of autophagy: unanswered questions. J Cell Sci. 118:7-18. Klionsky, DJ, Cueva R, and Yaver DS (1992) Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. J Cell Biol. 119:287-299. Klionsky, DJ and Emr SD (1989) Membrane protein sorting: biosynthesis, transport and processing of yeast vacuolar alkaline phosphatase. EMBO J. 8:2241-2250. Klionsky, DJ and Emr SD (1990) A new class of lysosomal/vacuolar protein sorting signals. J Biol Chem. 265:5349-5352. Klionsky, DJ and Ohsumi Y (1999) Vacuolar import of proteins and organelles from the cytoplasm. Annu Rev Cell Dev Biol. 15:1-32. Komatsu, M, Waguri S, Chiba T, Murata S, Iwata JI, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, and Tanaka K (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880-884. Kopitz, J, Kisen GO, Gordon PB, Bohley P, and Seglen PO (1990) Nonselective autophagy of cytosolic enzymes by isolated rat hepatocytes. J Cell Biol. 111:941-953. Kouno, T, Mizuguchi M, Tanida I, Ueno T, Kanematsu T, Mori Y, Shinoda H, Hirata M, Kominami E, and Kawano K (2005) Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains. J Biol Chem. 280:24610-24617. Kouroku, Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, Ogawa S, Kaufman RJ, Kominami E, and Momoi T. (2006) ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 14:203-239. Longtine, MS, McKenzie A 3rd, Demarini DJ, Shah NG, Wach A, Brachat A, Philippsen P, and Pringle JR.(1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 10:953-961. McMahon, HT and Mills IG (2004) COP and clathrin-coated vesicle budding: different pathways, common approaches. Curr Opin Cell Biol. 16:379-391. McNiven, MA (2006a) Big gulps: specialized membrane domains for rapid receptor-mediated endocytosis. Trends Cell Biol. 16:487-492. McNiven, MA and Thompson HM (2006b) Vesicle formation at the plasma membrane and trans-Golgi network: the same but different. Science 313:1591-1594. Mizushima, N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, Suzuki K, Tokuhisa T, Ohsumi Y, and Yoshimori T (2001) Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol. 152:657-668. Mizushima, N, Ohsumi Y, and Yoshimori T (2002) Autophagosome formation in mammalian cells. Cell Struct Funct. 27:421-429. Monastyrska, I and Klionsky DJ (2006) Autophagy in organelle homeostasis: peroxisome turnover. Mol Aspects Med. 27:483-494. Nair, U and Klionsky DJ (2005) Molecular mechanisms and regulation of specific and nonspecific autophagy pathways in yeast. J Biol Chem. 280:41785-41788. Nakagawa, I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T, Nara A, Funao J, Nakata M, Tsuda K, Hamada S, and Yoshimori T. (2004) Autophagy defends cells against invading group A Streptococcus. Science 306:1037-1040. Nebauer, R, Rosenberger S, and Daum G (2007) Phosphatidylethanolamine, a limiting factor of autophagy in yeast strains bearing a defect in the carboxypeptidase Y pathway of vacuolar targeting. J Biol Chem. 282:16736-16743. Neel, NF, Schutyser E, Sai J, Fan GH and Richmond A (2005) Chemokine receptor internalization and intracellular trafficking. Cytokine Growth Factor Rev. 16:637-658. Noda, T, Matsuura A, Wada Y, and Ohsumi Y. (1995) Novel system for monitoring autophagy in the yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun. 210:126-132. Noda, T, Suzuki K, and Ohsumi Y (2002) Yeast autophagosomes: de novo formation of a membrane structure. Trends Cell Biol. 12:231-235. Oda, MN, Scott SV, Hefner-Gravink A, Caffarelli AD, and Klionsky DJ (1996) Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. J Cell Biol. 132:999-1010. Ogawa, M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, and Sasakawa C. (2005) Escape of intracellular Shigella from autophagy. Science 307:727-731. Paz, Y, Elazar Z, and Fass D (2000) Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p. J Biol Chem. 275: 25445-25450. Pickart, CM (2001) Mechanisms underlying ubiquitination. Annu Rev Biochem. 70:503-533. Pozo Navas, B, Lohner K, Deutsch G, Sevcsik E, Riske KA, Dimova R, Garidel P, and Pabst G (2005) Composition dependence of vesicle morphology and mixing properties in a bacterial model membrane system. Biochim Biophys Acta. 1716:40-48. Priault, M, Salin B, Schaeffer J, Vallette FM, di Rago JP, and Martinou JC (2005) Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ. 12:1613-1621. Ptacek, J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De Virgilio C, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, and Snyder M (2005) Global analysis of protein phosphorylation in yeast. Nature 438:679-684. Ravikumar, B, Duden R, and Rubinsztein DC (2002) Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet. 11:1107-1117. Reggiori, F, Wang CW, Nair U, Shintani T, Abeliovich H, and Klionsky DJ (2004) Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae. Mol Biol Cell. 15:2189-2204. Reinstein, E and Ciechanover A (2006) Narrative review: protein degradation and human diseases: the ubiquitin connection. Ann Intern Med. 145:676-684. Rich, KA, Burkett C, and Webster P (2003) Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol. 5:455-468. Rogers, SW and Rechsteiner M (1988) Degradation of structurally characterized proteins injected into HeLa cells. Effects of intracellular location and the involvement of lysosomes. J Biol Chem. 263:19843-19849. Schwede, T, Kopp J, Guex N, and Peitsch MC (2003) SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 31:3381-3385. Scott, SV, Hefner-Gravink A, Morano KA, Noda T, Ohsumi Y, and Klionsky DJ (1996) Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole. Proc Natl Acad Sci USA. 93:12304-12308. Scott, SV, Guan J, Hutchins MU, Kim J, and Klionsky DJ (2001) Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. Mol Cell. 7:1131-1141. Shintani, T, Huang WP, Stromhaug PE, and Klionsky DJ. (2002) Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. Dev Cell. 3:825-837. Shintani, T and Klionsky DJ (2004a) Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. J Biol Chem. 279: 29889-29894. Shintani, T and Klionsky DJ (2004b) Autophagy in health and disease: a double-edged sword. Science 306:990-995. Sikorski, RS and Hieter P (1989) A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122:19-27. Stangler, T, Mayr LM, and Willbold D (2002) Solution structure of human GABA (A) receptor-associated protein GABARAP: implications for biolgoical function and its regulation. J Biol Chem. 277:13363-13366. Sugawara, K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, and Inagaki F (2004) The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes Cells. 9:611-618. Suzuki, K, Kirisako T, Kamada Y, Mizushima N, Noda T, and Ohsumi Y (2001) The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 20:5971-5981. Suzuki, K, Kamada Y, and Ohsumi Y (2002) Studies of cargo delivery to the vacuole mediated by autophagosomes in Saccharomyces cerevisiae. Dev Cell. 3:815-824. Suzuki, K and Ohsumi Y (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett. 581:2156-2161. Takeshige, K, Baba M, Tsuboi S, Noda T, and Ohsumi Y (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol. 119:301-311. Tanida, I, Tanida-Miyake E, Ueno T, and Kominami E (2001) The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. J Biol Chem. 276:1701-1706. Tanida, I., Ueno T, and Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 36:2503-2518. Wang, CW and Klionsky DJ (2003) The molecular mechanism of autophagy. Mol Med. 9:65-76. Yorimitsu, T and Klionsky DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ. 12:1542-1552. Yorimitsu, T, Nair U, Yang Z, and Klionsky DJ (2006) Endoplasmic reticulum stress triggers autophagy. J Biol Chem. 281:30299-30304 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29083 | - |
dc.description.abstract | 細胞自噬作用是一種在演化上高度守衡的細胞內大分子物質分解機制,所有真核生物,從單細胞的酵母菌到哺乳動物細胞都會進行細胞自噬。當外在環境改變,例如養份供應匱乏時,細胞會藉由在細胞質內產生稱為自噬小泡的雙層膜狀構造來包裹一部分細胞質和大分子物質,甚至是整個胞器,並且運送至溶酶體或是酵母菌的液泡中進行分解。在這過程中所釋放出來的小分子,例如胺基酸等,會被用來合成新的蛋白質以幫助細胞適應改變後的環境。同時,細胞自噬作用也是維持真核細胞內部蛋白質正常代謝的重要機制。目前已經知道細胞自噬與許多退化性神經疾病亦有關聯,例如亨丁頓氏舞蹈症中的聚麩醯胺酸沉澱會誘發細胞產生自噬小泡來包裹並分解之,而失衡的細胞自噬活性與不正常累積的蛋白質聚合物造成的毒性可能是這類退化性神經疾病中神經元大量死亡的主因之一。此外細胞自噬作用也被發現和多細胞生物的胚胎發育、程式性細胞死亡、或是癌症的病理機制等皆有密切的關連。
在目前已知的31種細胞自噬相關蛋白中,Atg8是細胞自噬小泡生成過程中所必需的一種調控蛋白。它在細胞質中被合成之後會藉由一系列的後轉錄修飾作用最後在末端接上一個磷脂質。此外研究發現,細胞自噬的專一性運送物質Ape1的受體Atg19也和Atg8有直接的交互作用,顯示Atg8很可能也參與了細胞自噬作用中的被分解物篩選作用。但不論是Atg8所參與的自噬小泡生合成途徑,或被分解物篩選的確切機制皆尚不清楚。在本篇研究中,我利用定點突變的方法分離出六個Atg8表面的重要胺基酸殘基,並且將它們對應到所負責的生理功能上。其中,殘基Arg28、Tyr49和Leu50組成一個和Atg19結合的區位,同時殘基Tyr49和Leu50也是Atg8在合成後進行後轉錄修飾作用中所必須的。此外殘基Phe79會被蛋白酶Atg4所辨識來調控該修飾作用中的第一步驟,殘基Leu55則是參與在Atg4所調控的另一步驟:去脂質修飾反應。另外一個殘基,Lys48則很可能參與在Atg8所調控的自噬小泡生成作用中。 | zh_TW |
dc.description.abstract | Autophagy is a highly conserved membrane trafficking pathway, which is evoked during stress condition, such as nutrient starvation. Excess or abnormal intracellular macromolecules are sequestered by the double-membrane vesicle, autophagosome, and transported to the vacuole/lysosome for degradation and recycling of nutrient. The released amino acids are used in synthesis of proteins required for cells to adapt to the changed environment. Atg8 is an essential regulator for autophagosome biogenesis. It is post-translationally conjugated to lipid at its C-terminus and is proposed to be the membrane modifier that may be functionally similar to coat proteins. Besides, Atg8 also interacts directly with the autophagic cargo receptor, Atg19. We are interested in whether the Atg8-mediated vesicle expansion process and cargo sorting are coupled. Here we identified 6 residues on Atg8 surface that are required for the modification and/or physiological function of it. Residue Arg28 is specific for the cargo receptor binding; Tyr49, Leu50, Leu55, and Phe79 are involved in different steps of its post-translational modification; and Lys48 is important for perhaps the biogenesis of autophagosome. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T00:38:59Z (GMT). No. of bitstreams: 1 ntu-96-R94b41021-1.pdf: 1857935 bytes, checksum: 9e30d1bef02c1b6fd5f92d8281b4b4ff (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | Acknowledgements ………………………………………………… 2
Abstract in Chinese ……………………………………………… 3 Abstract ………………………………………………………… 4 Introduction ……………………………………………………… 5 Materials and Methods …………………………………………11 Result ………………………………………………………………18 Discussion …………………………………………………………33 References …………………………………………………………39 Tables ………………………………………………………………52 Figures ………………………………………………………………57 Postscrip ……………………………………………………………77 | |
dc.language.iso | en | |
dc.title | 細胞自噬蛋白Atg8表面的功能區域之定性分析 | zh_TW |
dc.title | Characterization of different functional sites of Atg8 in Saccharomyces cerevisiae | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊寧寧(Nin-Nin Chuang),陳俊宏(Jiun-Hong Chen),李心予(Hsinyu Lee) | |
dc.subject.keyword | 細胞自噬,第八號細胞自噬蛋白,被分解物質篩選機制,蛋白質後轉錄脂質修飾, | zh_TW |
dc.subject.keyword | autophagy,Atg8,cargosorting,lipidation, | en |
dc.relation.page | 77 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-25 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
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