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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 陳瑞華(Ruey-Hwa Chen) | |
dc.contributor.author | Tse-Hsiang Chen | en |
dc.contributor.author | 陳澤翔 | zh_TW |
dc.date.accessioned | 2021-06-07T18:06:10Z | - |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-24 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16236 | - |
dc.description.abstract | The Cullin-RING E3 Ligases (CRLs) control many important cellular processes by using a family of BTB/POZ domain proteins as substrate adaptors. The mechanisms that regulate the action of this family of E3 ligases have not been completely understood. In this thesis, we identified IVNS1ABP (ND1) as an interacting protein of KLHL20, a Cullin3 (Cul3) substrate adaptor previously identified in our laboratory. Similar to KLHL20, ND1 consists of a BTB/POZ domain and six-tandem kelch repeats. Uniquely, ND1 can neither bind to Cul3 nor serve a KLHL20 substrate. Rather, ND1 stabilizes Cul3-KLHL20 E3 ligases substrate PML through decreasing PML ubiquitination level under normoxia or hypoxia condition. Analysis of the underlying molecular mechanism revealed that ND1 perturbs the function of Cul3-KLHL20 E3 ligases by interfering with the KLHL20-PML and KLHL20-Cul3 interaction. Moreover, lost-of-function analysis showed that ND1 knock-down decreases PML protein level and reduces PML ubiquitination, supporting the physiological role of ND1 in KLHL20-dependent PML regulation. In consistent with our findings, ND1 is able to attenuate the blockage effect of KLHL20 on PML-induced growth inhibition. Taken together, our studies identified ND1 as a negative regulator of the Cul3-KLHL20 E3 ligase via its interaction with KLHL20. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:06:10Z (GMT). No. of bitstreams: 1 ntu-101-R99448005-1.pdf: 2859529 bytes, checksum: 919747ea6327293cf4a7a9cd32a05b13 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 摘要 1
Abstract 2 Introduction 5 1. Ubiquitin-proteasome system 5 1.1 E3 ligases 6 1.2 Cullin-RING ligases 8 2. BTB/POZ protein family 10 2.1 KLHL20 11 2.2 IVNS1ABP 12 3. Regulation of Cullin-RING E3 ligases 14 4. Promyelocytic leukemia protein 16 Materials & Methods 20 Plasmids 20 Antibodies and reagents 21 Cell culture and transient transfection 22 Purification of GST-fusion protein from E. coli IPTG-induction system 23 GST pull-down assay 24 Immunoprecipitation 24 Western blot 25 Purification of proteins from baculovirus expression system 25 In vivo ubiquitination assay 26 In vitro ubiquitination assay 26 Establishment of ND1 knockdown cell lines by lentivirus system 27 Cell proliferation assay 28 Results 29 Identification of ND1 as a KLHL20 interacting protein 29 ND1 interacts with KLHL20 through its kelch repeats 30 ND1 isn’t a substrate of Cul3-KLHL20 ubiquitin E3 ligase 31 ND1 decreases KLHL20-mediated PML degradation 32 ND1 compromises KLHL20-induced PML degradation through decreasing PML ubiquitination level 33 ND1 decreases cul3-KLHL20 E3 ligase function on PML by disrupting the interaction of KLHL20 with both PML and Cul3 35 ND1 knock-down decreases PML protein level and reduces PML ubiquitination 35 ND1 attenuates the blockage effect of KLHL20 on PML-induced growth inhibition 36 Discussion 38 References 44 Figures 50 | |
dc.language.iso | en | |
dc.title | 探討ND1對Cullin3-KLHL20接合酶酵素之調控機制 | zh_TW |
dc.title | ND1 functions as a negative regulator of the Cullin3-KLHL20 ubiquitin E3 Ligase | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 施修明(Hsiu-Ming Shih),吳君泰(June-Tai Wu) | |
dc.subject.keyword | 泛素化,BTB/POZ區塊,CRLs,Cullin3,ND1,KLHL20,PML, | zh_TW |
dc.subject.keyword | Ubiquitination,BTB/POZ domain,CRLs,Cullin3,ND1,KLHL20,PML, | en |
dc.relation.page | 68 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-07-24 | |
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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