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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 呂勝春(Sheng-Chung Lee) | |
| dc.contributor.author | Ya-Huei Lin | en |
| dc.contributor.author | 林雅慧 | zh_TW |
| dc.date.accessioned | 2021-06-08T06:56:20Z | - |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-07-26 | |
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Trojanowski and Virginia M.-Y. Lee. (2008) Enrichment of C-terminal fragments in TAR DNA-binding protein-43 cytoplasmic inclusions in brain but not in spinal cord of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The American Journal of Pathology 173, 182-194. 26. Manuela Neumann, Ian R. Mackenzie, Nigel J. Cairns, Philip J. Boyer, William R. Markesbery, Charles D. Smith, J. Paul Taylor, Hans A. Kretzschmar, Virginia E. Kimonis, and Mark S. Forman. (2007) TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP Gene mutations. J. Neuropathol. Exp. Neurol. 66, 152-157. 27. M. Lamar Seibenhener, Jeganathan Ramesh Babu, Thangiah Geetha, Hing C. Wong,N. Rama Krishna, and Marie W. Wooten. (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol. Cell. Biol. 24, 8055-8068. 28. M. Lamar Seibenhener, Thangiah Geetha, Marie W. Wooten. (2007) Sequestosome 1/p62 - More than just a scaffold. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25855 | - |
| dc.description.abstract | SIK2 為AMPK 家族的一員，目前已知參與於荷爾蒙訊號傳導的調控和脂肪細胞的分化。然而SIK2 的其他功能目前仍不清楚。先前我們實驗室發現SIK2 和p97 有交互作用且調控ERAD。在本篇研究，我們探討SIK2 在處理蛋白質聚集體中所扮演的角色。我們使用MG132 和部分缺失的TDP43 來誘導包涵體和聚集體的形成。我們發現SIK2 和p97 坐落在蛋白質包涵體和聚集體上。當細胞表現沒有激酶活性的SIK2 或者減少其表現量時，會導致蛋白質聚集體增加，顯示SIK2 即有可能參與處
理蛋白質聚集體中。此外，SIK2 透過影響p97 的活性來調控蛋白質據集體的處理過程。進一步的研究顯示，SIK2 可能會影響自噬體的更新。 本篇研究顯示SIK2作為正向調控者，來影響蛋白質聚集體的降解。 | zh_TW |
| dc.description.abstract | SIK2 (salt-inducible kinase 2) belongs to members of AMPK family. The functions of SIK2 other than the regulation of insulin signal transduction and adipocyte differentiation are poorly understood. Recently, we showed that SIK2 interacts with p97 to regulate ER-associated protein degradation (ERAD). In this study, we further demonstrated that SIK2 plays important function in aggresome processing. Using proteasome inhibitor (e.g., MG132)- and C-terminal truncated TDP-43-induced inclusion bodies/aggresomes as models, we found that SIK2 and p97 co-localize to
aggresomes. Overexpression of SIK2 caused decrease while knockdown of SIK2 resulted in increase of inclusion bodies/aggresomes. It may facilitate aggresome processing through interacting with p97. Further experiments suggest that SIK2 may influence the turnover of autophagosomes. Our study demonstrated that SIK2 could serve as a positive regulator in autophagic-mediated protein degradation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T06:56:20Z (GMT). No. of bitstreams: 1 ntu-98-R96448006-1.pdf: 13710978 bytes, checksum: 72532fb69155cd7729b3a72a19696204 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | Master Thesis …………………………………………………………………i
中文摘要 …………………………………………………………………....ii ABSTRACT.....................................................................................................iii CONTENTS ……………………………………………………………...…iv INTRODUCTION .............................................................................................1 MATERIAL AND MEHTODS ...........................................................................5 DNA constructs, shRNAs and antibodies ……………………..……………….5 Cell culture and transfection ……………...……………….………………6 Site-directed mutagenesis …………………………………...………………6 Analysis of soluble and insoluble fraction …………………...………………..7 Immunofluorescence staining and quantification of aggresome-containing cells …..7 Analysis of clearance of protein aggregates ………………………….………...8 RESULTS ………………………………………………………………9 Association p97 and SIK2 with inclusion bodies and aggresome …………………………9 SIK2 may regulate aggresome processing ……………………………………10 SIK2 is required for aggresome clearance ……………………………………11 p97 is a substrate of SIK2 ………………………………………………….12 SIK2 promotes aggresome processing through p97 S770 ……………….……..12 SIK2 is colocalized with p62 …………………………………………….…13 SIK2 may be involved in autophagy-mediated aggresome degradation…………..14 DISCUSSION ……………………………………………………………….15 REFERENCE ……………………………………………………………….18 FIGURES ……………………………………………………...………….. 25 Fig.1 Endogenous p97 and SIK2 associate with aggresome ……….…..……….29 Fig. 2 SIK2 may regulate aggresome processing ……………………….……..33 Fig.3 SIK2 is required for aggresome clearance ………………………….….. 35 Fig. 4 p97 is a substrate of SIK2 ………………………...………………….36 Fig. 5 SIK2 promotes aggresome processing through p97 S770 ………………..37 Fig. 6 SIK2 is colocalized with p62 …………………………………………38 Fig. 7 SIK2 is involved in autophagic-mediated aggresomes degradation ……….39 | |
| dc.language.iso | en | |
| dc.subject | p97 | zh_TW |
| dc.subject | SIK2 | zh_TW |
| dc.subject | 蛋白質聚集體 | zh_TW |
| dc.subject | p97 | en |
| dc.subject | SIK2 | en |
| dc.subject | aggresomes | en |
| dc.title | SIK2在處理蛋白質聚集體中所扮演的角色 | zh_TW |
| dc.title | The Role of SIK2 in Aggresome Processing | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 施修明,吳君泰 | |
| dc.subject.keyword | SIK2,p97,蛋白質聚集體, | zh_TW |
| dc.subject.keyword | SIK2,p97,aggresomes, | en |
| dc.relation.page | 39 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2009-07-27 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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