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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 董馨蓮 | |
dc.contributor.author | Yun-Hui Chen | en |
dc.contributor.author | 陳韻卉 | zh_TW |
dc.date.accessioned | 2021-06-13T01:18:46Z | - |
dc.date.available | 2016-10-07 | |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-03 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29785 | - |
dc.description.abstract | CBM複合體(CARMA1-BCL10-MALT1)廣泛存在於各種不同種類的細胞中;而在近年來的研究中發現,CBM複合體於TCR/BCR這條活化NF-κB的訊息途徑中扮演不可或缺的角色,並有研究指出在NF-κB活化時BCL10的C端Serine/Threonine Rich Domain有磷酸化的修飾。所以本論文以定點突變及小片段刪除方式將BCL10的Serine進行突變,進而探討磷酸化於細胞中扮演的生理意義及功能為何。
首先將構築好的BCL10突變型於293T細胞中大量表現,結果顯示合併D1 (∆134-150)及Serine170及Serine171的突變型中,無法觀察到BCL10高分子量的磷酸化修飾,進一步以點突變方式重新構築BCL10 5SA (將Serine134、136、138、141、144突變成Alanine)模擬BCL10 D1,發現5SA-S170,171A與D1-S170,171A皆無磷酸化修飾,但二個突變型皆對於下游NF-κB的活性與絲狀構造的產生皆無太大影響。 接著我們建立一個內生性BCL10 Knock Down的Jurkat T細胞株,將BCL10 D1-S170,171A與5SA-S170,171A以Restore方式送回細胞觀察;結果顯示si-BCL10 Jurkat T細胞(BCL10表現量為野生株的4%)在處理TPA/Ionomycin刺激活化後,確實影響了IκBα的降解作用及p65的進核現象。最後以TPA/Ionomycin刺激細胞活化後,觀察細胞貼附於細胞外基質(Fibronectin)的能力,結果顯示si-BCL10 Jurkat T細胞之貼附能力大約為野生株的35 %左右,證實將BCL10 Knock Down後的確會降低Jurkat T細胞貼附於Fibronectin的能力。 | zh_TW |
dc.description.abstract | Recent studies have identified CARMA1 (Caspase Recruitment Domain, CARD, Membrane-Associated Guanylate Kinase, MAGUK, protein 1), BCL10 (B Cell Lymphoma 10) and MALT1 (Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1) as signalling compounds that have crucial and specific roles in T Cell receptor and B Cell receptor-induced NF-κB activation. Previous studies have demonstrated that BCL10 is phosphorylated in the C-terminal Serine/Threonine rich domain upon NF-κB activation.
In the present study, site-directed mutagenesis was utilized to generate BCL10 mutants to determine the critical phosphorylation sites on BCL10. Overexpression of BCL10 in 293T cells autonomously induced the highly-molecular weight phosphorylation isoforms of BCL10. Deletion of amino acid residues 134-150 (BCL10 D1) along with mutations at Serine170 and Serine171 completely abolished the appearance of the highly-molecular weight phosphorylation isoforms. BCL10 5SA with mutations at Serine134, 136, 138, 141, 144 mimicked the effect of BCL10 D1 mutant. These results indicated that Serine 134, 136, 138, 141, 144, 170, 171 were major phosphorylated residues on BCL10. The two un-phosphorylated mutants retained their abilities to activate NF-κB, and formed filamentous structure upon over-expression in 293T cell. Lentiviral transduction was utilized to generate BCL10 gene silencing Jurkat T cells (si-BCL10 Jurkat T cells) to investigate the physiological relevance of these phosphorylation sites. si-BCL10 Jurkat T cells (BCL10 expression decreased to 4% of Wild Type) showed poor ability to activate TPA/Ionomycin-induced NF-κB activation as evidenced by the inefficacy of degradation of IκBα and the failure in translocation of NF-κB subunit-p65 (RelA) to nucleus. Silencing of BCL10 induced a clear defect in TPA/Ionomycin-induced cell adhesion to fibronectin (decreased to 35% of Wild Type). These results pointed to a key role of BCL10 in the response of T cells upon activation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T01:18:46Z (GMT). No. of bitstreams: 1 ntu-100-R98445115-1.pdf: 3737701 bytes, checksum: a88f8d563adc572e150d3ea4ad07bff6 (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 目錄.............................................................................................................................. vi 第一章、 緒論............................................................................................................. 1 A. NF-κB Signaling Pathway基本介紹....................................................................... 1 | |
dc.language.iso | zh-TW | |
dc.title | BCL10磷酸化功能之探討 | zh_TW |
dc.title | Investigation on the Functional Roles of BCL10 Phosphorylation | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 蔡錦華,李明學 | |
dc.subject.keyword | CBM複合體,BCL10,磷酸化修飾,Gene Knock Down,細胞貼附, | zh_TW |
dc.subject.keyword | CBM Complex,BCL10, Phosphorylation,Gene Knock Down,,Adhesion., | en |
dc.relation.page | 76 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-03 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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