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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐立中(Li-Chung Hsu) | |
| dc.contributor.author | Chia-I Lien | en |
| dc.contributor.author | 連佳儀 | zh_TW |
| dc.date.accessioned | 2021-05-15T17:51:16Z | - |
| dc.date.available | 2019-10-09 | |
| dc.date.available | 2021-05-15T17:51:16Z | - |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-15 | |
| dc.identifier.citation | Adhikari, A., M. Xu, and Z.J. Chen. 2007. Ubiquitin-mediated activation of TAK1 and IKK. Oncogene. 26:3214-3226.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5045 | - |
| dc.description.abstract | 先天性免疫系統是宿主體內抵禦外來病原體侵犯或是偵測體內細胞組織傷害的第一道防線。先天性免疫反應可藉由活化體內包括Toll like receptors (TLRs)在內各種不同的pattern recognition receptors (PRRs)偵測到病原體或壞死細胞釋放特有的分子結構(稱為pathogen associated-molecular patterns, PAMPs 或damage associated-molecular patterns, DAMPs)，啟動生物體內的發炎反應和抗病毒功能。然而發炎反應的失衡也會造成身體的損害，因此TLR所傳遞的訊息路徑需要受到精細的調控。我們實驗室先前發現了一個新的含有鋅指的蛋白質ZFAND5，其在巨噬細胞內的表現量會受到lipopolysaccharide (LPS)的刺激而增加。然而我們對於ZFAND5在TLRs訊息傳遞路徑內的功能還不甚清楚。在這篇研究中，我們欲釐清ZFAND5的在TLR4訊息路徑內的功能及機制。我們發現在ZFAND5表現量降低的情況下施予LPS刺激，轉錄因子IRF-3的活化有減少的趨勢，而另一個轉錄因子NF-κB的第二波活化也同樣有減低的情形。除此之外，我們發現TRAF3和ZFAND5之間有交互作用，且ZFAND5是利用其N端的A20-like Zinc finger部分和TRAF3產生交互作用。我們更進一步發現降低ZFAND5的表現量會造成LPS引發TRAF3的K63- linked polyubiquitin減少。綜合我們及先前的研究 ，ZFAND5在TLR4訊息路徑是扮演正向調控的功能。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-05-15T17:51:16Z (GMT). No. of bitstreams: 1 ntu-103-R01448002-1.pdf: 2518481 bytes, checksum: 2bd9d8f12d3bef721c59b6b14903eb45 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 口試委員會審定書 ........................................................................................ i
中文摘要 ...................................................................................................... iii Abstract ........................................................................................................ iv Introduction ................................................................................................... 3 Innate immunity .................................................................................... 3 Toll- Like Receptors.............................................................................. 4 TLRs signaling pathways: ..................................................................... 6 TIR-domain-containing adaptor proteins ...................................... 6 MyD88-dependent pathway .......................................................... 6 TRIF-dependent pathway .............................................................. 8 TLR4 signaling .............................................................................. 9 Ubiquitination in TLRs signaling........................................................ 10 Zinc finger containing proteins ........................................................... 12 Zinc finger containing proteins induced by TLRs signaling ...... 12 ZFAND5 ...................................................................................... 13 Specific aim ................................................................................................. 15 Material and Method ................................................................................... 16 Antibodies and reagents ...................................................................... 16 Plasmids............................................................................................... 17 Cell culture .......................................................................................... 18 Transfection ......................................................................................... 19 Generation of stable ZFAND5 knockdown cells ................................ 19 Preparation of whole cell lysate .......................................................... 20 Preparation of bone marrow derived macrophages (BMDMs)........... 21 Immunoblotting ................................................................................... 22 Immunoprecipitation ........................................................................... 23 Results ......................................................................................................... 24 ZFAND5 depletion reduced activation of late phase of NF-κB and IRF3. .................................................................................................... 24 TRAF3 was identified as a new ZFAND5-interacting protein. .......... 25 ZFAND5 interacted with TRAF3 through its A20-like Zinc finger domain. ................................................................................................ 26 2 ZFAND5 depletion resulted in decreased K63-linked ubiquitination of TRAF3 in 264.7 macrophages after LPS stimulation. ........................ 26 Figures ......................................................................................................... 28 Figure 1. Depletion of ZFAND5 in RAW264.7 macrophages resulted in decreased activation of IRF3 and late phase of IKK after LPS stimulation. .......................................................................................... 29 Figure 2. Depletion of ZFAND5 in BMDMs decreased activation of IRF3 and late phase of IKK after LPS stimulation. ............................ 31 Figure 3. LPS-induced MAPKs activation was similar in control and ZFAND5-depleded Raw 264.7 cells. .................................................. 32 Figure 4. ZFAND5 interacted with TRAF3, but not MyD88 or TRIF ............................................................................................................. 35 Figure 5. ZFAND5 did not associate with TBK1 or TRAF2. ............ 36 Figure 6. ZFAND5 interacted with TRAF3 through its A20-like Zinc finger domain. ..................................................................................... 39 Figure 7. ZFAND5 depletion reduced LPS-induced K63-linked ubiquitination of TRAF3 in Raw 264.7 macrophages. ....................... 40 Figure 8. A proposed model for the role of ZFAND5 in the regulatation of TLR4-mediated response. ........................................... 41 Supplementary Figure 1. ZFAND5 depletion did not affect LPS-induced MAPKs activation. ........................................................ 43 Discussion ................................................................................................... 44 References ................................................................................................... 51 | |
| dc.language.iso | en | |
| dc.subject | 鋅指蛋白 | zh_TW |
| dc.subject | Zinc finger protein | en |
| dc.title | 一個新穎的鋅指蛋白於TLR4所調控的免疫反應中所扮演的功能探討 | zh_TW |
| dc.title | The functional role of a novel Zinc finger protein in the regulation of TLR4-mediated immune responses | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 胡孟君,盧主欽 | |
| dc.subject.keyword | 鋅指蛋白, | zh_TW |
| dc.subject.keyword | Zinc finger protein, | en |
| dc.relation.page | 55 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2014-08-18 | |
| 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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