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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄭永銘(Yung-Ming Jeng) | |
| dc.contributor.author | Chih-Ning Chang | en |
| dc.contributor.author | 張至寧 | zh_TW |
| dc.date.accessioned | 2021-06-13T07:06:28Z | - |
| dc.date.available | 2016-10-07 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-07-22 | |
| dc.identifier.citation | 6. Reference
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35717 | - |
| dc.description.abstract | Cdk1在細胞週期和染色體濃縮中扮演一個重要的角色，然而其機制仍尚未明瞭。經由DNA微陣列的分析，我們發現Repo-Man過度表現在肝細胞癌中。先前研究指出Repo-Man是1號γ型蛋白去磷酸酶 (PP1γ)的結合伴侶，會在細胞分裂時調控染色體濃縮，但其功能如何調控目前尚未明瞭。 在本篇論文中，我們發現在細胞分裂早期Repo-Man會被Cdk1磷酸化。喪失磷酸化機能的突變型Repo-Man會在細胞分裂的前期和中期提前轉位至染色體上，抑制染色體濃縮。染色體濃縮遭到抑制會在細胞分裂後期和末期造成染色體橋，以及在細胞分裂結束後產生微細胞核。磷酸化的Repo-Man會於細胞分裂後期招攬PP1γ至染色體上。而突變形的Repo-Man 會於細胞分裂前期與中期提前招攬PP1γ至染色體，造成組蛋白H3 (Histone H3)於3號羥丁氨酸過早去磷酸化。我們的研究結果顯示Cdk1磷酸化的Repo-Man會於細胞分裂早期將Repo-Man-PP1γ複合體排除於染色體外，使得Histone H3 於3號羥丁氨酸可被磷酸化，進而導致細胞分裂早期的染色體濃縮。 | zh_TW |
| dc.description.abstract | Cyclin-dependent kinase 1 (Cdk1) is a key player in cell cycle regulation, yet the mechanism of regulating chromosome condensation is not fully known. Using microarray analysis, we found Repo-Man is a gene overexpressed in hepatocellular carcinoma. Repo-Man is originally identified as a binding partner for protein phosphatase 1γ. A previous study found Repo-Man is implicated in regulation of chromosome condensation during mitosis, but the mechanism is still unknown. We propose a novel finding that Repo-Man is phosphorylated by Cdk1 in early mitosis. Phosphorylation null Repo-Man prematurely translocates to chromosomes in prophase and metaphase and inhibits chromosome condensation. The inhibition of chromosome condensation results in chromosomal bridging in anaphase and telophase and micronuclei formation after mitosis. Phosphorylated Repo-Man recruits protein phosphatase 1γ (PP1γ) onto chromosome at the onset of anaphase. Phosphorylation null Repo-Man prematurely recruits PP1γ onto chromatin in prophase and metaphase, leading to premature dephosphorylation of Histone H3 Thr3. The data indicate that Cdk1 phosphorylates Repo-Man to exclude the binding of Repo-Man-PP1γ complex on chromosome in early mitosis and induces full phosphorylation of Histone H3 Thr3 to induce chromosome condensation in early mitosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T07:06:28Z (GMT). No. of bitstreams: 1 ntu-100-R98444005-1.pdf: 2056478 bytes, checksum: b3f55b0a56d8cca3ed38fd8fba689011 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Contents
PAGE 口試委員審定書: II 致謝: III 中文摘要: IV ABSTRACT: V CONTENTS VI 1. INTRODUCTION 1 1.1 CYCLIN-DEPENDENT KINASES (CDKS) 1 1.2 CYCLIN-DEPENDENT KINASE 1 (CDK1) 2 1.3 REGULATION OF CHROMOSOME CONDENSATION BY CDK1 6 1.4 THE FUNCTION OF REPO-MAN 9 1.5 THE FUNCTION OF PP1Γ 12 1.6 PURPOSES OF STUDY 14 2. MATERIALS AND METHODS 15 2.1 CELL CULTURE 15 2.2 CONSTRUCTION OF REPO-MAN AND PP1Γ PLASMID 15 2.3 MUTAGENESIS 16 2.4 CELL CYCLE SYNCHRONIZATION 16 2.5 IMMUNOPRECIPITATION 17 2.6 WESTERN BLOT 18 2.7 IN VITRO KINASE ASSAY 19 2.8 TRANSFECTION AND VIRAL INFECTION 20 2.9 IMMUNOFLUROESCENT STAINING 20 2.10 CHROMOSOME SPREADING ANALYSIS 22 2.11 RNAI KNOCKDOWN OF REPO-MAN 22 2.12 RT-PCR 23 3. RESULTS 24 3.1 REPO-MAN IS OVEREXPRESSED IN HEPATOCELLULAR CARCINOMA 24 3.2 REPO-MAN IS PHOSPHORYLATED AT G2/M 25 3.3 THE SUBCELLULAR LOCALIZATION OF REPO-MAN CHANGES THROUGHOUT CELL CYCLE 26 3.4 REPO-MAN IS BINDING TO AND PHOSPHORYLATED BY CDK1 26 3.5 THE SUBCELLULAR LOCATION OF REPO-MAN WITH CDK1 INHIBITOR TREATMENT 28 3.6 SUBCELLULAR LOCALIZATION OF REPO-MAN PHOSPHORYLATION NULL MUTANT 28 3.7 PHOSPHORYLATION NULL MUTANT REPO-MAN INDUCES FAILURE OF CONDENSATION OF CHROMOSOME AND MICRONUCLEI FORMATION 30 3.8 THE SUBCELLULAR LOCATION OF PHOSPHO-HISTONE H3 AT THR3 31 3.9 PHOSPHORYLATION OF HISTONE H3 AT THR3 IN CELLS WITH REPO-MAN KNOCKDOWN 32 4. DISCUSSION 33 4.1 OVEREXPRESSION OF REPO-MAN IN SEVERAL TYPES OF CANCERS 33 4.2 PHOSPHORYLATION OF REPO-MAN IS REGULATED BY CDK1 IN G2/M 34 4.3 THE SUBCELLULAR LOCALIZATION OF REPO-MAN REGULATED BY CDK1 35 4.4 CHROMOSOME CONDENSATION REGULATED BY REPO-MAN 37 4.5 CONCLUSION 43 5. TABLES AND FIGURES 45 TABLE 1. PRIMERS USED IN THIS STUDY 45 FIGURE 1. REPO-MAN IS PHOSPHORYLATED IN G2/M PHASE DURING THE CELL CYCLE 46 FIGURE 2. SUBCELLULAR LOCALIZATION OF REPO-MAN THROUGHOUT CELL CYCLE 47 FIGURE 3. REPO-MAN BINDS TO AND IS PHOSPHORYLATED BY CDK1. 48 FIGURE 4. SUBCELLULAR LOCALIZATION OF EGFP-REPO-MAN IN ROSCOVITINE TREATED HELA CELLS. 49 FIGURE 5. MUTATION SITE OF NULL MUTANT AND SUBCELLULAR LOCALIZATION OF REPO-MAN 51 FIGURE 6. THE CHROMOSOME SPREADING ANALYSIS OF WILDTYPE AND NULL MUTANT OF REPO-MAN TRANSDUCED HELA CELLS 52 FIGURE 7. MICRONUCLEI WERE INCREASED IN NULL MUTANT REPO-MAN TRANSDUCED CELLS AFTER MITOSIS. 53 FIGURE 8. PHOSPHORYLATION OF HISTONE H3 THR3 AT MITOSIS 55 FIGURE 9. PHOSPHORYLATION OF HISTONE H3 THR3 IN REPO-MAN KNOCKED DOWN HELA CELLS 57 FIGURE 10. SUBCELLULAR LOCALIZATION AND MOLECULAR MECHANISM OF REPO-MAN IN CELL CYCLE 60 6. REFERENCE 61 | |
| dc.language.iso | en | |
| dc.subject | 染色體濃縮 | zh_TW |
| dc.subject | Cdk1 | zh_TW |
| dc.subject | Repo-Man | zh_TW |
| dc.subject | PP1γ | zh_TW |
| dc.subject | 細胞分裂 | zh_TW |
| dc.subject | Repo-Man | en |
| dc.subject | Cdk1 | en |
| dc.subject | chromosome condensation | en |
| dc.subject | mitosis | en |
| dc.subject | PP1γ | en |
| dc.title | 細胞分裂中Cdk1對Repo-Man磷酸化對染色體濃縮的影響 | zh_TW |
| dc.title | Phosphorylation of Repo-Man by Cdk1 Regulates Chromosome Condensation in Mitosis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 譚賢明(Bertrand Tan),周涵怡(Han-Yi Chou),張亨? | |
| dc.subject.keyword | Cdk1,Repo-Man,PP1γ,細胞分裂,染色體濃縮, | zh_TW |
| dc.subject.keyword | Cdk1,Repo-Man,PP1γ,mitosis,chromosome condensation, | en |
| dc.relation.page | 69 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-07-22 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-100-1.pdf 未授權公開取用 | 2.01 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。