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  2. 醫學院
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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41031
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dc.contributor.advisor李芳仁
dc.contributor.authorHsu-Feng Wuen
dc.contributor.author吳旭豐zh_TW
dc.date.accessioned2021-06-14T17:12:52Z-
dc.date.available2016-10-05
dc.date.copyright2011-10-05
dc.date.issued2011
dc.date.submitted2011-08-11
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41031-
dc.description.abstractADP-ribosylation factor-like (ARL) 4C is a member of Ras-related small G protein family. Previous studies have shown that ARL4C plays potential roles in actin dynamics and cholesterol secretion process. However the cellular function of ARL4C remains unclear. We found that exogenous wild type ARL4C and active form ARL4C-Q72L induced filopodia and reduced stress fiber intensity in HeLa cell. Overexpression of Cdc42-T17N or Rac1-T17N did not affect ARL4C-induced filopodia. We found that the expression level of ARL4C mRNA could be detected by RT-PCR in human lung adenocarcinoma cell line (CL1-5). Wound-healing assay showed that migration ability was decreased in ARL4C-depleted CL1-5. To identify potential effectors of ARL4C, We performed yeast two-hybrid screening in human fetal brain cDNA library by using ARL4C-Q72L as bait and identified a putative effector of ARL4C, an actin-binding protein filamin A (FLNa). Yeast two‐hybrid analysis showed that the C-terminus of FLNa interacted with wild type ARL4C and ARL4C-Q72L, but not with ARL4C inactive form T27N. GST-Pull down assay and immunoprecipitation demonstrated that ARL4C interacted with the FLNa in vitro and in vivo. Immunofluorescence analysis showed that wild type ARL4C and ARL4C-Q72L colocalized with endogenous FLNa at plasma membrane and ARL4C-induced filopodia in HeLa cells. Knockdown of FLNa by siRNA did not affect the localization of ARL4C or ARL4C-induced filopodia. In the future, we will study the roles of ARL4C and FLNa in CL1-5 cell migration ability.en
dc.description.provenanceMade available in DSpace on 2021-06-14T17:12:52Z (GMT). No. of bitstreams: 1
ntu-100-R97448009-1.pdf: 20217798 bytes, checksum: 6c7aae035baaa03feb82459c1fe393bd (MD5)
Previous issue date: 2011
en
dc.description.tableofcontentsTable of Contents...............................................................................................................1
中文摘要...........................................................................................................................3
Abstract.............................................................................................................................4
Abbreviations....................................................................................................................6
1. Introduction
1.1. Small GTPases of Ras Superfamily........................................................................7
1.2. Arf Family of GTPases...........................................................................................8
1.3. ADP-ribosylation factor-like 4C (ARL4C)..........................................................10
1.4. Lung adenocarcinoma (CL1-0/CL1-5).................................................................11
1.5. Filamin A (FLNa).................................................................................................12
2. Material and Method
2.1. Cell Culture and Transfection...............................................................................14
2.2. Expression Plasmids.............................................................................................14
2.3. Immunostaining....................................................................................................15
2.4. SDS‐PAGE and Immunoblotting Analysis..........................................................15
2.5. Yeast Two‐Hybrid Screen and Interaction Assay................................................16
2.6. Preparation of Recombinant Proteins...................................................................17
2.7. GST Pull Down Assay..........................................................................................18
2.8. Reverse Transcription PCR (RT-PCR).................................................................18
2.9. Preparation of Yeast protein Extracts by TCA Method.......................................19
2.10. Immunoprecipitation..........................................................................................19
2.11. Small Interference RNA.....................................................................................20
2.12. Wound-Healing Assay........................................................................................20
3. Result
3.1. Subcellular localization of ARL4C or its mutants in HeLa cells.........................22
3.2. Overexpression of Cdc42-T17N or Rac1-T17N did not affect the
ARL4C-induced filopodia in HeLa cells.............................................................23
3.3. Detection of endogenous ARL4C in different cell lines......................................23
3.4. The effect of ARL4C knockdown in CL1-5.........................................................24
3.5. Identification of putative ARL4C-Q72L interacting Proteins..............................26
3.6. FLNa specifically interacted with wild type ARL4C and ARL4C-Q72L............26
3.7. Identification of specific ARL4C-interacting region within FLNa......................27
3.8. FLNa could bind with ARL4C in vitro and in vivo..............................................27
3.9. Subcellular localization of endogenous FLNa in HeLa cells...............................28
3.10. Knockdown of FLNa did not affect ARL4C-induced filopodia in HeLa cells..29
4. Discussion....................................................................................................................31
5. Tables, Figures, and Supplementary Figures...............................................................36
6. Reference.....................................................................................................................64
dc.language.isoen
dc.subject二磷酸核醣化相似因子四Czh_TW
dc.subject腺嘌呤核&#33527zh_TW
dc.subjectARL4Cen
dc.title腺嘌呤核苷二磷酸核醣化相似因子四C (ARL4C)與其結合蛋白之特性探討zh_TW
dc.titleCharacterization of ARL4C and its putative effectoren
dc.typeThesis
dc.date.schoolyear99-2
dc.description.degree碩士
dc.contributor.oralexamcommittee陳瑞華,張智芬,周祖述
dc.subject.keyword腺嘌呤核&#33527,二磷酸核醣化相似因子四C,zh_TW
dc.subject.keywordARL4C,en
dc.relation.page68
dc.rights.note有償授權
dc.date.accepted2011-08-12
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept分子醫學研究所zh_TW
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