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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳瑞華(Ruey-Hwa Chen) | |
| dc.contributor.author | Ruei-Liang Yan | en |
| dc.contributor.author | 顏睿良 | zh_TW |
| dc.date.accessioned | 2021-06-16T08:46:06Z | - |
| dc.date.available | 2025-07-09 | |
| dc.date.copyright | 2020-08-26 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-07-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59038 | - |
| dc.description.abstract | 細胞自噬為真核生物中具高度保留性的機制，可透過降解細胞自身物質，並將其回收再利用以對抗飢餓逆境。當今科學發展已闡明了細胞自噬在許多疾病中所扮演的角色，然其中之詳細分子機制則尚未明朗。此外，長鏈非編碼RNA在近年也引起了廣泛的關注，因其能參與調控許多的生物途徑，其中包括細胞自噬。然而，多數調控細胞自噬的長鏈非編碼RNA，主要為調節細胞自噬相關基因的表現。本研究中，我們發現一新穎長鏈非編碼RNA BCRP3，能作為基礎及飢餓條件下，細胞自噬的正向調控者。我們發現BCRP3基因敲落會損害自噬小體，及早期自噬相關結構的形成，但卻不會影響更上游的基酶活性，包含:ULK1、AMPK及mTOR。有趣的是，RNA pulldown與RNA免疫沉澱分析皆顯示BCRP3會與Vps34聚合體結合。儘管這樣的交互作用不影響Vps34聚合體的完整性，以及Beclin-1的寡聚化，BCPR3能夠直接地提升Vps34聚合體的酵素活性。此外，我們也發現BCRP3表現量會在蛋白酶體抑制所引發的細胞自噬中有所上升。綜觀而言，我們的研究揭示了BCRP3做為細胞自噬正向調控者的角色，透過提升Vps34聚合體的活性來促進Vps34所介導的自噬啟動，並暗示了BCRP3上調對蛋白酶體抑制誘導的細胞自噬的貢獻。 | zh_TW |
| dc.description.abstract | Autophagy is a conserved self-eating process for recycling metabolic building blocks during starvation. Recent advances have elucidated the role of autophagy in many diseases, but the molecular detail is not fully understood. To date, long non-coding RNAs (lncRNAs) have drawn great attention as important regulators in different biological processes, including autophagy. However, most of the autophagy-modulating lncRNAs function by regulating autophagy-related gene expression. Here, we identified a novel lncRNA BCRP3 as a positive regulator of autophagy in basal and starvation conditions. We showed that BCRP3 depletion impairs the formation of autophagosome and also the early autophagic structures, omegasome and phagophore. However, BCRP3 deficiency does not change the kinase activities of ULK1, AMPK and mTOR. Interestingly, BCRP3 associates with multiple subunits of Vps34 complex as detected by RNA pulldown and RNA immunoprecipitation assays. However, BCRP3 affects neither the integrity of Vps34 complex nor the oligomerization of Beclin-1. Instead, BCRP3 directly increases the enzymatic activity of Vps34 complex both in vivo and in vitro. We further showed that BCRP3 is upregulated upon proteasome inhibition, a condition known to induce autophagy. Together, our data reveal the function of BCRP3 as a positive regulator of autophagy by promoting Vps34-mediated autophagy initiation and suggest a contribution of BCRP3 upregulation to proteasome inhibition-induced autophagy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T08:46:06Z (GMT). No. of bitstreams: 1 U0001-0807202014412200.pdf: 1972808 bytes, checksum: 30dc3f54073fb4f0d3878ccdf78cdf4c (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 論文口試委員審定書 謝辭...................................................................................................................................i 中文摘要..........................................................................................................................ii Abstract ............................................................................................................................iii I. Introduction ..........................................................................................................1 1. Autophagy.........................................................................................................1 1-1. Physiological and pathological view of autophagy.............................1 1-2. Autophagosome biogenesis and maturation........................................3 1-3. Structural and functional regulation of PI3K complex........................8 2. Long non-coding RNA (lncRNA)..................................................................10 2-1. Characteristics of lncRNA................................................................10 2-2. Cellular functions of lncRNA............................................................11 2-3. lncRNA in autophagy........................................................................13 II. Materials and Methods.........................................................................................17 Plasmids...........................................................................................................17 Oligonucleotides..............................................................................................17 Antibodies........................................................................................................17 Chemicals........................................................................................................19 Primers.............................................................................................................19 Cell Culture and Transfection..........................................................................20 Lentiviral package and transduction.................................................................20 Western Blotting..............................................................................................20 Immunoprecipitation.......................................................................................21 Immunofluorescence.......................................................................................21 Quantitative real-time PCR (qRT-PCR) ..........................................................22 Subcellular fractionation assay........................................................................22 RNA immunoprecipitation..............................................................................23 RNA pull-down assay......................................................................................23 PI3K kinase assay............................................................................................24 III. Results.................................................................................................................26 IV. Discussions..........................................................................................................32 V. References...........................................................................................................42 VI. Figures.................................................................................................................58 | |
| dc.language.iso | en | |
| dc.subject | 長鏈非編碼RNA | zh_TW |
| dc.subject | Beclin-1 | zh_TW |
| dc.subject | Vps34聚合體 | zh_TW |
| dc.subject | 細胞自噬 | zh_TW |
| dc.subject | autophagy | en |
| dc.subject | Beclin-1 | en |
| dc.subject | Vps34 complex | en |
| dc.subject | lncRNA | en |
| dc.title | 一新穎長鏈非編碼RNA透過活化Vps34 複合體來促進細胞自噬的啟動 | zh_TW |
| dc.title | A novel lncRNA facilitates autophagy initiation through the activation of Vps34 complex | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳光超(Guang-Chao Chen),蔡欣祐(Hsin-Yue Tsai) | |
| dc.subject.keyword | 細胞自噬,長鏈非編碼RNA,Vps34聚合體,Beclin-1, | zh_TW |
| dc.subject.keyword | autophagy,lncRNA,Vps34 complex,Beclin-1, | en |
| dc.relation.page | 70 | |
| dc.identifier.doi | 10.6342/NTU202001384 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-07-13 | |
| 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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