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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳俊任(Chun-Jen Chen) | |
dc.contributor.author | Han-Jen Chang | en |
dc.contributor.author | 張瀚壬 | zh_TW |
dc.date.accessioned | 2021-06-13T04:21:44Z | - |
dc.date.available | 2016-08-03 | |
dc.date.copyright | 2011-08-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-27 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33007 | - |
dc.description.abstract | Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and play important roles in the innate immune response. Signaling of most TLRs require the adaptor molecule MyD88, except for TLR3 which signals through TRIF. Upon binding of virus-derived double-stranded RNAs, TLR3 initiates a signaling cascade involving TRIF, TRAF3, TBK1 and IKKε, resulting in the phosphorylation and nuclear translocation of IRF3 which activates the transcription of type I interferons. Among these signaling molecules, IKKε and IRF3 are reported to be modified by the small ubiquitin-like modifier (SUMO). Since TRAF3 also contains several consensus sites of SUMOylation, we initiated this study to determine whether TRAF3 is also modified by SUMO. Co-immunopreciptation experiments show that TRAF3 is associated with SUMO1; however, the SUMO1-associated TRAF3 has no increase in molecular weight that corresponds to SUMO1 conjugation, raising the possibility that TRAF3 interacts with SUMO1 in a non-covalent way. Experiments using TRAF3 deleted of N-terminus or C-terminus show that the N-terminal half of TRAF3 is responsible for SUMO1 association. Further truncational analysis indicates that the N-terminal RING domain plays a critical role for the interaction. We also found that TRAF3 is associated with Ubc9 (the SUMO conjugating enzyme) in a RING domain-dependent manner. Moreover, overexprssion of TRAF3 enhances SUMOylation of an unidentified protein of around 130 kDa. These results suggest that TRAF3 may act as a SUMO E3 ligase. Studies are underway to elucidate the mechanism of the interaction between SUMO and TRAF3. Further investigations on how SUMOylation affects TRAF3 function and signaling should provide more insights into how the TLR3 pathway is regulated during an antiviral response. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T04:21:44Z (GMT). No. of bitstreams: 1 ntu-100-R98b47103-1.pdf: 1232246 bytes, checksum: 318227eafc97c7e068aa5e5cadfff99c (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract iv Abbreviation vi Introduction 1 1. The Small Ubiquitin-Like Modifier (SUMO) Protein Modification System 1 1.1 The SUMO family 1 1.2 Mechanism of SUMO conjugation 3 1.3 The role of RING domain in SUMO E3 ligase 5 1.4 SUMOylation and immune response 6 2. TNF receptor associated factor 3 (TRAF3) 7 2.1 TNF receptor associated factors family 7 2.2 The role of TRAF3 in immune response 8 2.3 Toll-like Receptor 3 (TLR3) signaling pathway and SUMOylation 10 2.4 Rationale of this study 11 Specific Aims 13 Materials and Methods 14 1. SUMOylation site prediction 14 2. Plasmids and construction 14 3. Transfection 15 4. Preparation of whole cell lysates 15 5. Co-immunoprecipitation 16 6. SDS-PAGE and Western blotting 16 Results 18 1. TRAF3 is associated with SUMO1 non-covalently 18 2. The RING domain on TRAF3 N-terminus is crucial for the association between TRAF3 and SUMO1 19 3. TRAF3 is associated with Ubc9 20 4. The RING domain on TRAF3 is also critical for the interaction between TRAF3 and Ubc9 20 5. TRAF3 promotes the SUMOylation of an unidentified protein 21 6. TRAF3 may promote the SUMOylation of TBK1 21 Discussion 23 Figures and Tables 28 References 38 | |
dc.language.iso | en | |
dc.title | TRAF3 與 SUMO 相關分子間交互作用之研究 | zh_TW |
dc.title | Studies on the interaction between TRAF3 and SUMO-associated molecules | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 張世宗(Shih-Chung Chang) | |
dc.contributor.oralexamcommittee | 徐立中(Li-Chung Hsu) | |
dc.subject.keyword | SUMO 化修飾系統,SUMO E3 黏合酶,TRAF3,TLR3路徑, | zh_TW |
dc.subject.keyword | SUMO,SUMO E3 ligase,TRAF3,TLR3 pathway, | en |
dc.relation.page | 47 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-07-27 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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