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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳宏文 | |
| dc.contributor.author | Chang-Chun Wang | en |
| dc.contributor.author | 王昶鈞 | zh_TW |
| dc.date.accessioned | 2021-06-08T05:14:42Z | - |
| dc.date.copyright | 2011-08-04 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-01 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24042 | - |
| dc.description.abstract | FBW2 contains an F-box motif and is a substrate recognition subunit of SCF E3 ligase complex. The WD40 domain in FBW2 binds the substrate for ubiquitination and proteasomeal degradation. Although the SCF E3 ligase activity may be regulated by post-translational modification such as neddylation of its scaffold protein Cullin, it is possible that regulation of FBW2 activity may also affect the SCFFBW2 E3 ligase activity. In the present study, we used tandem affinity purification combined with LC/MS/MS to identify RACK1 (receptor for activated C-kinase 1) as an FBW2-associated protein that regulates FBW2-mediated ubiquitination.
RACK1 is a scaffold protein, which contains seven WD40 repeats, and interacts with many proteins in multiple signal transduction pathways. In this study, we found RACK1 interacts with FBW2 in vivo and in vitro. By domain mapping analysis and in vitro competition experiments, we found that RACK1 interacts with the WD40 domain of FBW2 to block the interaction between FBW2 and its substrate GCM1. Accordingly, an in vivo ubiquitination assay showed that ubiquitination of exogenous GCM1 is enhanced in 293T cells when RACK1 is knocked down. Moreover, the protein level of endogenous GCM1 is decreased in RACK1-knockdown placental BeWo cells. In line with these observations, overexpression of RACK1 increases GCM1-mediated transcriptional activation. Overall, our results indicate that RACK1 may repress FBW2 activity by protecting its substrate from degradation and suggest a new role of RACK1 in regulation of E3 ligase activity. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T05:14:42Z (GMT). No. of bitstreams: 1 ntu-100-R98b46022-1.pdf: 4067140 bytes, checksum: 5e4e55ba0ec38caea9d9b2ca5908dc79 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 目錄………………………………………………………………………………...…… I
中文摘要……………………………………………………………………………… III 英文摘要…………………………………………………………………………….....IV 第一章 緒論 1.1 泛素-蛋白酶體系統……..................................................................... 1 1.2 FBW2蛋白….........................................................................................3 1.3 RACK1鷹架式結構蛋白…………………………………...................6 1.4 研究動機…………………………………...………………………….8 第二章 材料及方法 2.1 串聯式親合性純化和質譜儀分析........................................................9 2.2 重組質體的構築……………………………………………………..10 2.3 重組蛋白在人類細胞的表現………………………….….................13 2.4 細胞蛋白萃取及處理………………………………………………. 14 2.5 SDS聚丙烯醯胺凝膠電泳及西方墨點法………………………….. 15 2.6 共同免疫沉澱法…………………………………………................. 16 2.7 活體外交互作用分析………………………………………………. 16 2.8 免疫螢光染色…………..................................................................... 17 2.9 活體內泛素化作用分析………………………………..................... 18 2.10 Luciferase螢光報告基因活性檢測…………………………………18 2.11 RNA干擾和慢病毒感染…………………………………………….19 第三章 實驗結果 3.1 鑑定RACK1為與FBW2互相作用的蛋白…………………...…….. 20 3.2 RACK1和FBW2的交互作用……………………………...….. 20 3.3 RACK1結合FBW2的WD40結構區域…………………………...….23 3.4 RACK1降低FBW2和其受質蛋白間的結合……………………. …24 3.5 RACK1對細胞內GCM1汎素化的影響……………………….. ...…25 3.6 RACK1能相對提高GCM1的轉錄活性……………......... ……...….26 3.7 胎盤細胞中RACK1對GCM1蛋白穩定度的影響……….......... …...27 第四章 討論與總結 4.1 RACK1影響SCFFBW2的功能和活性…………………………………28 4.2 RACK1在胎盤細胞中的生理意義……………………………...…...29 第五章 圖表…………………………………………………………………………...31 第六章 參考文獻…………………………………………………………….. …........46 | |
| dc.language.iso | zh-TW | |
| dc.subject | WD40 結構區域 | zh_TW |
| dc.subject | 鷹架式結構蛋白 | zh_TW |
| dc.subject | FBW2 | zh_TW |
| dc.subject | RACK1 | zh_TW |
| dc.subject | SCF 複合體 | zh_TW |
| dc.subject | scaffold protein | en |
| dc.subject | FBW2 | en |
| dc.subject | RACK1 | en |
| dc.subject | SCF complex | en |
| dc.subject | WD40 domain | en |
| dc.title | 探討RACK1鷹架式結構蛋白對FBW2活性的調控 | zh_TW |
| dc.title | Regulation of FBW2 Activity by RACK1 Scaffold Protein | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李明亭,張震東,張功耀,張茂山 | |
| dc.subject.keyword | FBW2,RACK1,SCF 複合體,WD40 結構區域,鷹架式結構蛋白, | zh_TW |
| dc.subject.keyword | FBW2,RACK1,SCF complex,WD40 domain,scaffold protein, | en |
| dc.relation.page | 51 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2011-08-01 | |
| 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 | |
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