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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 | 鄧述諄(Shu-Chun Teng) | |
dc.contributor.author | Yi-Ci Ke | en |
dc.contributor.author | 柯怡綺 | zh_TW |
dc.date.accessioned | 2021-06-17T08:28:15Z | - |
dc.date.available | 2019-08-26 | |
dc.date.copyright | 2019-08-26 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-12 | |
dc.identifier.citation | Alekseev OM, Bencic DC, Richardson RT, Widgren EE, O'Rand MG. (2002). Overexpression of the Linker histone-binding protein tNASP affects progression through the cell cycle. J Biol Chem 278, 8846-8852.
Bae MK, Jeong JW, Kim SH, Kim SY, Kang HJ, Kim DM, Bae SK, Yun I, Trentin GA, Rozakis-Adcock M, Kim KW. (2005). Tid-1 interacts with the von Hippel-Lindau protein and modulates angiogenesis by destabilization of HIF-1alpha. Cancer Res 65, 2520-2525. Blagosklonny MV, Wu GS, Omura S, el-Deiry WS. (1996). Proteasome-dependent regulation of p21WAF1/CIP1 expression. Biochem Biophys Res Commun 227, 564-569. Braakman I and Bulleid NJ. (2011). Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem 80, 71-99. Brehme M, Voisine C, Rolland T, Wachi S, Soper JH, Zhu Y, Orton K, Villella A, Garza D, Vidal M, Ge H, Morimoto RI. (2014). A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep 9, 1135-1150. Calderwood SK, Murshid A, Prince T. (2009). The shock of aging: molecular chaperones and the heat shock response in longevity and aging--a mini-review. Gerontology 55, 550-558. Chen YC, Jiang PH, Chen HM, Chen CH, Wang YT, Chen YJ, Yu CJ, Teng SC. (2018). Glucose intake hampers PKA-regulated HSP90 chaperone activity. Elife 7. Chen KC, Qu S, Chowdhury S, Noxon IC, Schonhoft JD, Plate L, Powers ET, Kelly JW, Lander GC, Wiseman RL. (2017). The endoplasmic reticulum HSP40 co-chaperone ERdj3/DNAJB11 assembles and functions as a tetramer. EMBO J 15, 2296-2309. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A. (2006). Opposing activities protect against age-onset proteotoxicity. Science 313, 1604-1610. Cook AJ, Gurard-Levin ZA, Vassias I, Almouzni G. (2011). A specific function for the histone chaperone NASP to fine-tune a reservoir of soluble H3-H4 in the histone supply chain. Mol Cell 44, 918-927. Finn RM, Ellard K, Eirín-López JM, Ausió J. (2012). Vertebrate nucleoplasmin and NASP: egg histone storage proteins with multiple chaperone activities. FASEB J 26, 4788-4804. Fewell SW, Travers KJ, Weissman JS, Brodsky JL. (2001). The action of molecular chaperones in the early secretory pathway. Annu Rev Genet 35, 149-191. Gartel AL, Serfas MS, Tyner AL. (1996). p21--negative regulator of the cell cycle. Proc Soc Exp Biol Med 213, 138-149. Gartel AL and Radhakrishnan SK. (2005). Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res 65, 3980-3985. Genereux JC, Qu S, Zhou M, Ryno LM, Wang S, Shoulders MD, Kaufman RJ, Lasmézas CI, Kelly JW, Wiseman RL. (2015). Unfolded protein response-induced ERdj3 secretion links ER stress to extracellular proteostasis. EMBO J 34, 4-19. Gorenberg EL, Chandra SS. (2017). The Role of Co-chaperones in Synaptic Proteostasis and Neurodegenerative Disease. Front Neurosci 11,248. Guo F and Snapp EL. (2013). ERdj3 regulates BiP occupancy in living cells. J Cell Sci 126, 1429-1439. Jan CI, Yu CC, Hung MC, Harn HJ, Nieh S, Lee HS, Lou MA, Wu YC, Chen CY, Huang CY, Chen FN, Lo JF. (2011). Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients. J Pathol 225, 424-437. Jascur T, Brickner H, Salles-Passador I, Barbier V, El Khissiin A, Smith B, Fotedar R, Fotedar A. (2005). Regulation of p21(WAF1/CIP1) stability by WISp39, a Hsp90 binding TPR protein. Mol Cell 17, 237-249. Jin Y, Zhuang M, Hendershot LM. (2009). ERdj3, a luminal ER DnaJ homologue, binds directly to unfolded proteins in the mammalian ER: identification of critical residues. Biochemistry 48, 41-49. Kim SW, Chao TH, Xiang R, Lo JF, Campbell MJ, Fearns C, Lee JD. (2004). Tid1, the human homologue of a Drosophila tumor suppressor, reduces the malignant activity of ErbB-2 in carcinoma cells. Cancer Res 21, 7732-7739. Lempiäinen H and Halazonetis. (2009). Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J 28, 3067-3073. Levy G. (2007). The relationship of Parkinson disease with aging. Arch Neurol 64, 1242-1246. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. (2013). The hallmarks of aging. Cell 153, 1194-1217. Iosefson O, Sharon S, Goloubinoff P, Azem A. (2012). Reactivation of protein aggregates by mortalin and Tid1--the human mitochondrial Hsp70 chaperone system. Cell Stress Chaperones 17, 57-66. Lovejoy CA and Cortez D. (2009). Common mechanisms of PIKK regulation. DNA Repair 8, 1004-1008. Maréchal A and Zou L. (2013). DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol 5. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ. (2007). ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-1166. McKeen HD, McAlpine K, Valentine A, Quinn DJ, McClelland K, Byrne C, O'Rourke M, Young S, Scott CJ, McCarthy HO, Hirst DG, Robson T. (2008). A novel FK506-like binding protein interacts with the glucocorticoid receptor and regulates steroid receptor signaling. Endocrinology 149, 5724-5734. Muthuswamy SK, Gilman M, Brugge JS. (1999). Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol Cell Biol 10, 6845-6857. Oliveira AV, Vilaça R, Santos CN, Costa V, Menezes R. (2017). Exploring the power of yeast to model aging and age-related neurodegenerative disorders. Biogerontology 18, 3-34. Qiu XB, Shao YM, Miao S, Wang L. (2006). The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 63, 2560-2570. Richardson RT, Batova IN, Widgren EE, Zheng LX, Whitfield M, Marzluff WF, O'Rand MG. (2000). Characterization of the histone H1-binding protein, NASP, as a cell cycle-regulated somatic protein. J Biol Chem 275, 30378-30386. Ruipérez V, Darios F, Davletov B. (2010). Alpha-synuclein, lipids and Parkinson’s disease. Prog Lipid Res 49, 420-428. Shen Y and Hendershot LM. (2005). ERdj3, a stress-inducible endoplasmic reticulum DnaJ homologue, serves as a cofactor for BiP's interactions with unfolded substrates. Mol Biol Cell 1, 40-50. Shiber A, Ravid T. (2014). Chaperoning proteins for destruction: diverse roles of Hsp70 chaperones and their co-chaperones in targeting misfolded proteins to the proteasome. Biomolecules 4, 704-724. Shoulders MD, Ryno LM, Genereux JC, Moresco JJ, Tu PG, Wu C, Yates JR 3rd, Su AI, Kelly JW, Wiseman RL. (2013). Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments. Cell Rep 3, 1279-1292. Stokes MP, Rush J, Macneill J, Ren JM, Sprott K, Nardone J, Yang V, Beausoleil SA, Gygi SP, Livingstone M, Zhang H, Polakiewicz RD, Comb MJ. (2007). Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci U S A 104, 19855-19860. Syken J, De-Medina T, Münger K. (1999). TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two mitochondrial modulators of apoptosis with opposing functions. Proc Natl Acad Sci U S A 96, 8499-8504. Takayama S, Xie Z, Reed JC. (1999). An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem 274, 781-786. Trinh DL, Elwi AN, Kim SW. (2010). Direct interaction between p53 and Tid1 proteins affects p53 mitochondrial localization and apoptosis. Oncotarget 6, 396-404. Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L. (2002). Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc Natl Acad Sci U S A 99, 12847-12852. Zhou P, Fernandes N, Dodge IL, Reddi AL, Rao N, Safran H, DiPetrillo TA, Wazer DE, Band V, Band H. (2003). ErbB2 degradation mediated by the co-chaperone protein CHIP. J Biol Chem 278, 13829-13837. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74291 | - |
dc.description.abstract | 蛋白質不正常摺疊與堆積在神經退化性疾病中視為重要的病理特徵,在許多的文獻當中也指出老化為造成神經退化性疾病的重要因素。造成老化原因有很多像是氧化壓力以及DNA 受損等,當細胞面臨這些壓力時會啟動修復路徑,最主要的路徑為ATM與ATR,ATM/ATR會磷酸化下游的蛋白進而傳遞一些訊號。然而根據先前實驗室研究發現到分子伴侶 (chaperone/co-chaperone) 的磷酸化會影響到蛋白的摺疊及堆積,有鑑於此,我們推測在ATM/ATR磷酸化下游蛋白中的分子伴侶會影響神經退化性疾病中的蛋白堆積。因此我們根據先前大規模分析在壓力下ATM/ATR磷酸化的受質中挑出分子伴侶,在這11個可能的分子伴侶中進行初步篩選,發現到DNAJA3與DNAJB11蛋白的磷酸化對於下游受質有所影響。
DNAJA3與DNAJB11皆會使ErbB-2蛋白的量下降,ErbB-2為酪氨酸激酶接受器 (tyrosine kinase receptor),在我們的結果中發現到在DNAJA3 S169D與S169A突變後以及DNAJB11 T188E中,ErbB-2的量明顯下降,因此初步認為DNAJA3與DNAJB11的磷酸化是會去影響下游的受質。 | zh_TW |
dc.description.abstract | Protein aggregation can be found in a variety of diseases such as Parkinson’s and Alzheimer’s diseases. Many stresses at the molecular and cellular levels have been identified to provoke aging and play an important role in neurodegenerative diseases. Upon these stresses induce DNA damage response, ATM and ATR, two central regulators phosphorylate the downstream substrates to transduce signal. From the previous study, we found that the dephosphorylation of a co-chaperone facilitates protein folding under stresses. We speculate that the phosphorylation of chaperones/co-chaperones by stress/aging-induced ATM/ATR may also control the protein folding in neurodegenerative diseases. From the previous large-scale proteomic analysis of proteins phosphorylated by ATM/ATR in response to DNA damage, we found that 11 chaperones/co-chaperones phosphorylated. In my screening, the phosphorylation of DNAJA3 and DNAJB11 might be crucial for protein aggregations. Both DNAJA3 and DNAJB11 facilitate ErbB-2 degradation. DNAJA3 S169D and S169A, the mimetic phosphorylation and dephosphorylation mutations, reduced ErbB-2 than DNAJA3 mutations. However, DNAJB11 T188E, the mimetic phosphorylation, reduced ErbB-2 to a greater extent than DNAJB11 and DNAJB11 T188A. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T08:28:15Z (GMT). No. of bitstreams: 1 ntu-108-R06445110-1.pdf: 1684139 bytes, checksum: 214ac4bc0a118d3b2e55840db6c4d6b6 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員審定書 I
摘要 II ABSTRACT III INTRODUCTION 1 MATERIALS AND METHODS 4 RESULTS 8 DISCUSSION 16 FIGURES 18 TABLES 27 REFERENCES 29 | |
dc.language.iso | en | |
dc.title | 探討在神經退化性疾病裡分子伴侶如何調控蛋白堆積 | zh_TW |
dc.title | To Study the Regulation of Chaperone and Co-chaperone in Neurodegenerative Diseases | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳青錫(Ching-Shyi Wu),林靜嫻(Chin-Hsien Lin) | |
dc.subject.keyword | 分子伴侶,ATM/ATR,神經退化性疾病,蛋白磷酸化,老化,DNAJA3,DNAJB11,ErbB-2, | zh_TW |
dc.subject.keyword | chaperone/co-chaperone,ATM/ATR,neurodegenerative diseases,protein phosphorylation,aging,DNAJA3,DNAJB11,ErbB-2, | en |
dc.relation.page | 32 | |
dc.identifier.doi | 10.6342/NTU201903275 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-13 | |
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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