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???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
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dc.contributor.advisor | 陳小梨(Show-Li Chen) | |
dc.contributor.author | Chieh-Hao Su | en |
dc.contributor.author | 蘇捷豪 | zh_TW |
dc.date.accessioned | 2021-06-08T04:15:45Z | - |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-05 | |
dc.identifier.citation | Alimirah F, Panchanathan R, Chen J, Zhang X, Ho SM, Choubey D (2007) Expression of androgen receptor is negatively regulated by p53. Neoplasia 9: 1152-1159
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Annu Rev Biochem 65: 135-167 Yang Z, Chang YJ, Yu IC, Yeh S, Wu CC, Miyamoto H, Merry DE, Sobue G, Chen LM, Chang SS, Chang C (2007) ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat Med 13: 348-353 Zegarra-Moro OL, Schmidt LJ, Huang H, Tindall DJ (2002) Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res 62: 1008-1013 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22335 | - |
dc.description.abstract | DDB2 is a well-known WD40 protein that associates with DDB1 and involved in DDB1-Cul4 E3 complex. DDB1-DDB2 heterodimer was in nucleotide excision repair (NER) pathway which UV induced DNA damage repairs. AR, a well-studied molecule, is known to be highly expressed in prostate cancer and functions as an important transcription factor to regulate the expression of a great number of genes, then guides the prostate cancer cell into a malignant stage or maintains prostate cancer cell growth. We previously showed that DDB2 is a novel AR binding protein. Knockdown endogenous DDB1, CUL4A resulted in increased AR protein amount, implying that DDB2 may degrade AR protein via DDB1-CUL4 E3 ligase pathway. Here, we presented the DNA-damage inducing DDB2 that decreasing AR protein. After we introduced DDB2 in LNCaP cell results in the decreased AR protein. Moreover, knowckdown DDB2 expression in LNCaP cells increases AR protein. To demonstrate the mechanism of DDB2 destabilizing AR, we found that DDB2-N terminal domain can interact with AR, but only full length DDB2 has function to degrade AR. We also mapped that AR HBD domain is responsible for DDB2 binding. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:15:45Z (GMT). No. of bitstreams: 1 ntu-99-R97445121-1.pdf: 1648331 bytes, checksum: dd5e951af3ee2ce7d4e752bf8aa69857 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 口試委員會審定書
誌謝 中文摘要 ABSTRACT CHAPTER 1 INTRODUCTION…………………………………………….…………..1 1.1 DNA damage binding protein 2 (DDB2)….…………...………….…...1 1.2 The role of DDB2 in DNA damage and protein degradation......………2 1.3 Androgen receptor and its turnover………….…………………….......3 1.4 Nuclear receptor interaction protein (NRIP)…...………………….…...6 1.5 Aim of the Thesis…………………………………………...………….7 CHAPTER 2 MATERIAL AND METHODS…………………..……….9 2.1 Cell culture and Drug Treatment……………………………………….9 2.2 plasmid construction…………………………………….……………...9 2.3 UV irradiation………………………….……………………...………10 2.4 RNA interference…………………………………………...…………11 2.5 transient transfection…..…………………...…………………………12 2.6 in vitro GST pull down assay…………………………………………12 2.7 Western blot…..……… ………………………..……………………13 2.8 RNA extration……………………..…………………………………13 2.9 RT-PCR analysis ……………………………..……………………...14 2.10 Realtime PCR………………………………………...……………..16 2.11protein stability assay……………...………………………………...16 CHAPTER 3 RESULTS…………………………………...…………….18 3.1 DDB2 inhibits cellular AR protein expression in prostate cancer cells after DNA damage is p53 independent mann………………………...18 3.2 DDB2 decreases AR protein level……………………………………20 3.3 DDB2 triggers AR protein degradation via DDB1 Cul4ADDB2 E3 ligase complex………….................................................................................21 3.4 Mapping DDB2 domain responsible for AR binding and its consequence……………………………………………………...……22 3.5 DDB2 and NRIP share the same HBD domain on AR.........................23 3.6 NRIP-DM and DDB2 compete for binding to limiting amounts of AR…………………………………………………………………….24 CHAPTER 4 DISCCUSION……………………………………………26 REFERENCES …………………………………………………...……..34 FIGURES………………………………………………………...………40 APPENDIX………………………………………………………………51 | |
dc.language.iso | en | |
dc.title | DDB2降解雄性激素受體蛋白之探討 | zh_TW |
dc.title | DDB2 affacts on AR protein degradation | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄧述諄,吳君泰 | |
dc.subject.keyword | 雄性激素受體,DDB2,核受體交互作用蛋白, | zh_TW |
dc.subject.keyword | Cullin4,DDB1,DDB2,AR, | en |
dc.relation.page | 56 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-08-06 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
Appears in Collections: | 微生物學科所 |
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