DC 欄位 | 值 | 語言 |
dc.contributor | 呂勝春 | zh-TW |
dc.contributor | Lee, Sheng-Chung | en |
dc.contributor | 臺灣大學:分子醫學研究所 | zh-TW |
dc.contributor.author | 林雅慧 | zh-TW |
dc.contributor.author | Lin, Ya-Huei | en |
dc.creator | 林雅慧 | zh-TW |
dc.creator | Lin, Ya-Huei | en |
dc.date | 2009 | en |
dc.date.accessioned | 2010-05-04T07:12:13Z | - |
dc.date.accessioned | 2018-07-09T01:19:24Z | - |
dc.date.available | 2010-05-04T07:12:13Z | - |
dc.date.available | 2018-07-09T01:19:24Z | - |
dc.date.issued | 2009 | - |
dc.identifier.other | U0001-2407200911290800 | en |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/178736 | - |
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 toggresomes. 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 coulderve as a positive regulator in autophagic-mediated protein degradation. | en |
dc.description.tableofcontents | Master Thesis …………………………………………………………………i文摘要 …………………………………………………………………....iiBSTRACT.....................................................................................................iiiONTENTS ……………………………………………………………...…ivNTRODUCTION .............................................................................................1ATERIAL AND MEHTODS ...........................................................................5NA constructs, shRNAs and antibodies ……………………..……………….5ell culture and transfection ……………...……………….………………6ite-directed mutagenesis …………………………………...………………6nalysis of soluble and insoluble fraction …………………...………………..7mmunofluorescence staining and quantification of aggresome-containing cells …..7nalysis of clearance of protein aggregates ………………………….………...8ESULTS ………………………………………………………………9ssociation p97 and SIK2 with inclusion bodies and aggresome …………………………9IK2 may regulate aggresome processing ……………………………………10IK2 is required for aggresome clearance ……………………………………1197 is a substrate of SIK2 ………………………………………………….12IK2 promotes aggresome processing through p97 S770 ……………….……..12IK2 is colocalized with p62 …………………………………………….…13IK2 may be involved in autophagy-mediated aggresome degradation…………..14ISCUSSION ……………………………………………………………….15EFERENCE ……………………………………………………………….18IGURES ……………………………………………………...………….. 25ig.1 Endogenous p97 and SIK2 associate with aggresome ……….…..……….29ig. 2 SIK2 may regulate aggresome processing ……………………….……..33ig.3 SIK2 is required for aggresome clearance ………………………….….. 35ig. 4 p97 is a substrate of SIK2 ………………………...………………….36ig. 5 SIK2 promotes aggresome processing through p97 S770 ………………..37ig. 6 SIK2 is colocalized with p62 …………………………………………38ig. 7 SIK2 is involved in autophagic-mediated aggresomes degradation ……….39 | en |
dc.format | application/pdf | en |
dc.format.extent | 13710978 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language | en | en |
dc.language.iso | en_US | - |
dc.subject | SIK2 | zh-TW |
dc.subject | p97 | zh-TW |
dc.subject | 蛋白質聚集體 | zh-TW |
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.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/178736/1/ntu-98-R96448006-1.pdf | - |
item.languageiso639-1 | en_US | - |
item.fulltext | with fulltext | - |
item.grantfulltext | open | - |
顯示於: | 分子醫學研究所
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