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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48118完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳小梨(Show-Li Chen) | |
| dc.contributor.author | Szu-Wei Chang | en |
| dc.contributor.author | 張思為 | zh_TW |
| dc.date.accessioned | 2021-06-15T06:46:39Z | - |
| dc.date.available | 2016-10-07 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-06-17 | |
| dc.identifier.citation | Aarnisalo P, Palvimo JJ, Janne OA (1998) CREB-binding protein in androgen receptor-mediated signaling. Proc Natl Acad Sci U S A 95: 2122-2127
Abbate EA, Berger JM, Botchan MR (2004) The X-ray structure of the papillomavirus helicase in complex with its molecular matchmaker E2. Genes Dev 18: 1981-1996 Abbate EA, Voitenleitner C, Botchan MR (2006) Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association. Mol Cell 24: 877-889 Akgul B, Cooke JC, Storey A (2006) HPV-associated skin disease. J Pathol 208: 165-175 Auborn KJ (2002) Therapy for recurrent respiratory papillomatosis. Antivir Ther 7: 1-9 Backs J, Backs T, Bezprozvannaya S, McKinsey TA, Olson EN (2008) Histone deacetylase 5 acquires calcium/calmodulin-dependent kinase II responsiveness by oligomerization with histone deacetylase 4. Mol Cell Biol 28: 3437-3445 Bahler M, Rhoads A (2002) Calmodulin signaling via the IQ motif. FEBS Lett 513: 107-113 Baseman JG, Koutsky LA (2005) The epidemiology of human papillomavirus infections. J Clin Virol 32 Suppl 1: S16-24 Bellanger S, Demeret C, Goyat S, Thierry F (2001) Stability of the human papillomavirus type 18 E2 protein is regulated by a proteasome degradation pathway through its amino-terminal transactivation domain. J Virol 75: 7244-7251 Bellanger S, Tan CL, Nei W, He PP, Thierry F (2010) The human papillomavirus type 18 E2 protein is a cell cycle-dependent target of the SCFSkp2 ubiquitin ligase. J Virol 84: 437-444 Belliot G, Sosnovtsev SV, Mitra T, Hammer C, Garfield M, Green KY (2003) In vitro proteolytic processing of the MD145 norovirus ORF1 nonstructural polyprotein yields stable precursors and products similar to those detected in calicivirus-infected cells. J Virol 77: 10957-10974 Berrevoets CA, Doesburg P, Steketee K, Trapman J, Brinkmann AO (1998) Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2). Mol Endocrinol 12: 1172-1183 Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1: 11-21 Bikle DD, Oda Y, Xie Z (2005) Vitamin D and skin cancer: a problem in gene regulation. J Steroid Biochem Mol Biol 97: 83-91 Chan WK, Klock G, Bernard HU (1989) Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. J Virol 63: 3261-3269 Chang SW, Tsao YP, Lin CY, Chen SL (2011) NRIP, a novel calmodulin binding protein, activates calcineurin to dephosphorylate HPV E2 protein. J Virol Chen PH, Tsao YP, Wang CC, Chen SL (2008) Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stability. Nucleic Acids Res 36: 51-66 Collins LL, Lin DL, Mu XM, Chang C (2001) Feedback regulation between orphan nuclear receptor TR2 and human papilloma virus type 16. J Biol Chem 276: 27316-27321 Dao LD, Duffy A, Van Tine BA, Wu SY, Chiang CM, Broker TR, Chow LT (2006) Dynamic localization of the human papillomavirus type 11 origin binding protein E2 through mitosis while in association with the spindle apparatus. J Virol 80: 4792-4800 de Villiers EM (2003) Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma. Int J Cancer 103: 705-708 Demeret C, Desaintes C, Yaniv M, Thierry F (1997) Different mechanisms contribute to the E2-mediated transcriptional repression of human papillomavirus type 18 viral oncogenes. J Virol 71: 9343-9349 Dong G, Broker TR, Chow LT (1994) Human papillomavirus type 11 E2 proteins repress the homologous E6 promoter by interfering with the binding of host transcription factors to adjacent elements. J Virol 68: 1115-1127 Doorbar J (2005) The papillomavirus life cycle. J Clin Virol 32 Suppl 1: S7-15 Dostatni N, Lambert PF, Sousa R, Ham J, Howley PM, Yaniv M (1991) The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex. Genes Dev 5: 1657-1671 Fujimoto N, Yeh S, Kang HY, Inui S, Chang HC, Mizokami A, Chang C (1999) Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J Biol Chem 274: 8316-8321 Gagnon D, Joubert S, Senechal H, Fradet-Turcotte A, Torre S, Archambault J (2009) Proteasomal degradation of the papillomavirus E2 protein is inhibited by overexpression of bromodomain-containing protein 4. J Virol 83: 4127-4139 Gammoh N, Gardiol D, Massimi P, Banks L (2009) The Mdm2 ubiquitin ligase enhances transcriptional activity of human papillomavirus E2. J Virol 83: 1538-1543 Garcia-Alai MM, Gallo M, Salame M, Wetzler DE, McBride AA, Paci M, Cicero DO, de Prat-Gay G (2006) Molecular basis for phosphorylation-dependent, PEST-mediated protein turnover. Structure 14: 309-319 Gloss B, Bernard HU, Seedorf K, Klock G (1987) The upstream regulatory region of the human papilloma virus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO J 6: 3735-3743 Hadaschik D, Hinterkeuser K, Oldak M, Pfister HJ, Smola-Hess S (2003) The Papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation. J Virol 77: 5253-5265 Hamid NA, Brown C, Gaston K (2009) The regulation of cell proliferation by the papillomavirus early proteins. Cell Mol Life Sci 66: 1700-1717 Han CP, Lee MY, Tzeng SL, Yao CC, Wang PH, Cheng YW, Chen SL, Wu TS, Tyan YS, Kok LF (2008) Nuclear Receptor Interaction Protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization. J Exp Clin Cancer Res 27: 25 Hawley-Nelson P, Androphy EJ, Lowy DR, Schiller JT (1988) The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. EMBO J 7: 525-531 He YJ, McCall CM, Hu J, Zeng Y, Xiong Y (2006) DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev 20: 2949-2954 Hebner CM, Laimins LA (2006) Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity. Rev Med Virol 16: 83-97 Heinlein CA, Ting HJ, Yeh S, Chang C (1999) Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. J Biol Chem 274: 16147-16152 Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H (2006) CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat Cell Biol 8: 1277-1283 Hou SY, Wu SY, Zhou T, Thomas MC, Chiang CM (2000) Alleviation of human papillomavirus E2-mediated transcriptional repression via formation of a TATA binding protein (or TFIID)-TFIIB-RNA polymerase II-TFIIF preinitiation complex. Mol Cell Biol 20: 113-125 Hsiao PW, Chang C (1999) Isolation and characterization of ARA160 as the first androgen receptor N-terminal-associated coactivator in human prostate cells. J Biol Chem 274: 22373-22379 Huang CC, Wang JM, Kikkawa U, Mukai H, Shen MR, Morita I, Chen BK, Chang WC (2008) Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation. Oncogene 27: 2422-2429 Hubbert NL, Schiller JT, Lowy DR, Androphy EJ (1988) Bovine papilloma virus-transformed cells contain multiple E2 proteins. Proc Natl Acad Sci U S A 85: 5864-5868 Jia S, Kobayashi R, Grewal SI (2005) Ubiquitin ligase component Cul4 associates with Clr4 histone methyltransferase to assemble heterochromatin. Nat Cell Biol 7: 1007-1013 Jin J, Arias EE, Chen J, Harper JW, Walter JC (2006) A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell 23: 709-721 Kahl CR, Means AR (2003) Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev 24: 719-736 Kang HY, Yeh S, Fujimoto N, Chang C (1999) Cloning and characterization of human prostate coactivator ARA54, a novel protein that associates with the androgen receptor. J Biol Chem 274: 8570-8576 Khare S, Pater MM, Tang SC, Pater A (1997) Effect of glucocorticoid hormones on viral gene expression, growth, and dysplastic differentiation in HPV16-immortalized ectocervical cells. Exp Cell Res 232: 353-360 Kinoshita-Kikuta E, Aoki Y, Kinoshita E, Koike T (2007) Label-free kinase profiling using phosphate affinity polyacrylamide gel electrophoresis. Mol Cell Proteomics 6: 356-366 Komuves L, Oda Y, Tu CL, Chang WH, Ho-Pao CL, Mauro T, Bikle DD (2002) Epidermal expression of the full-length extracellular calcium-sensing receptor is required for normal keratinocyte differentiation. J Cell Physiol 192: 45-54 Kotake Y, Zeng Y, Xiong Y (2009) DDB1-CUL4 and MLL1 mediate oncogene-induced p16INK4a activation. Cancer Res 69: 1809-1814 Kovelman R, Bilter GK, Glezer E, Tsou AY, Barbosa MS (1996) Enhanced transcriptional activation by E2 proteins from the oncogenic human papillomaviruses. J Virol 70: 7549-7560 Kruppel U, Muller-Schiffmann A, Baldus SE, Smola-Hess S, Steger G (2008) E2 and the co-activator p300 can cooperate in activation of the human papillomavirus type 16 early promoter. Virology 377: 151-159 Kumar RA, Naidu SR, Wang X, Imbalzano AN, Androphy EJ (2007) Interaction of papillomavirus E2 protein with the Brm chromatin remodeling complex leads to enhanced transcriptional activation. J Virol 81: 2213-2220 Lacey CJ (2005) Therapy for genital human papillomavirus-related disease. J Clin Virol 32 Suppl 1: S82-90 Lee AY, Chiang CM (2009) Chromatin adaptor Brd4 modulates E2 transcription activity and protein stability. J Biol Chem 284: 2778-2786 Lee CW, Lin CC, Luo SF, Lee HC, Lee IT, Aird WC, Hwang TL, Yang CM (2008) Tumor necrosis factor-alpha enhances neutrophil adhesiveness: induction of vascular cell adhesion molecule-1 via activation of Akt and CaM kinase II and modifications of histone acetyltransferase and histone deacetylase 4 in human tracheal smooth muscle cells. Mol Pharmacol 73: 1454-1464 Lee D, Hwang SG, Kim J, Choe J (2002) Functional interaction between p/CAF and human papillomavirus E2 protein. J Biol Chem 277: 6483-6489 Little GH, Bai Y, Williams T, Poizat C (2007) Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells. J Biol Chem 282: 7219-7231 Longworth MS, Laimins LA (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68: 362-372 Lusky M, Fontane E (1991) Formation of the complex of bovine papillomavirus E1 and E2 proteins is modulated by E2 phosphorylation and depends upon sequences within the carboxyl terminus of E1. Proc Natl Acad Sci U S A 88: 6363-6367 McBride AA, McPhillips MG, Oliveira JG (2004) Brd4: tethering, segregation and beyond. Trends Microbiol 12: 527-529 McBride AA, Oliveira JG, McPhillips MG (2006) Partitioning viral genomes in mitosis: same idea, different targets. Cell Cycle 5: 1499-1502 McPhillips MG, Oliveira JG, Spindler JE, Mitra R, McBride AA (2006) Brd4 is required for e2-mediated transcriptional activation but not genome partitioning of all papillomaviruses. J Virol 80: 9530-9543 Mittal R, Tsutsumi K, Pater A, Pater MM (1993) Human papillomavirus type 16 expression in cervical keratinocytes: role of progesterone and glucocorticoid hormones. Obstet Gynecol 81: 5-12 Mohr IJ, Clark R, Sun S, Androphy EJ, MacPherson P, Botchan MR (1990) Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 250: 1694-1699 Moodley M, Moodley J, Chetty R, Herrington CS (2003) The role of steroid contraceptive hormones in the pathogenesis of invasive cervical cancer: a review. Int J Gynecol Cancer 13: 103-110 Muller A, Ritzkowsky A, Steger G (2002) Cooperative activation of human papillomavirus type 8 gene expression by the E2 protein and the cellular coactivator p300. J Virol 76: 11042-11053 Muller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schule R (2000) FHL2, a novel tissue-specific coactivator of the androgen receptor. EMBO J 19: 359-369 Ng DC, Su MJ, Kim R, Bikle DD (1996) Regulation of involucrin gene expression by calcium in normal human keratinocytes. Front Biosci 1: a16-24 Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55: 74-108 Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ (2000) AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins. J Virol 74: 5872-5879 Penrose KJ, Garcia-Alai M, de Prat-Gay G, McBride AA (2004) Casein Kinase II phosphorylation-induced conformational switch triggers degradation of the papillomavirus E2 protein. J Biol Chem 279: 22430-22439 Penrose KJ, McBride AA (2000) Proteasome-mediated degradation of the papillomavirus E2-TA protein is regulated by phosphorylation and can modulate viral genome copy number. J Virol 74: 6031-6038 Rehtanz M, Schmidt HM, Warthorst U, Steger G (2004) Direct interaction between nucleosome assembly protein 1 and the papillomavirus E2 proteins involved in activation of transcription. Mol Cell Biol 24: 2153-2168 Rhoads AR, Friedberg F (1997) Sequence motifs for calmodulin recognition. FASEB J 11: 331-340 Romanczuk H, Thierry F, Howley PM (1990) Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol 64: 2849-2859 Schweiger MR, You J, Howley PM (2006) Bromodomain protein 4 mediates the papillomavirus E2 transcriptional activation function. J Virol 80: 4276-4285 Scrima A, Konickova R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, Nakatani Y, Iwai S, Pavletich NP, Thoma NH (2008) Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. Cell 135: 1213-1223 Shai A, Pitot HC, Lambert PF (2008) p53 Loss synergizes with estrogen and papillomaviral oncogenes to induce cervical and breast cancers. Cancer Res 68: 2622-2631 Tan SH, Leong LE, Walker PA, Bernard HU (1994) The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID. J Virol 68: 6411-6420 Thierry F (2009) Transcriptional regulation of the papillomavirus oncogenes by cellular and viral transcription factors in cervical carcinoma. Virology 384: 375-379 Thierry F, Dostatni N, Arnos F, Yaniv M (1990) Cooperative activation of transcription by bovine papillomavirus type 1 E2 can occur over a large distance. Mol Cell Biol 10: 4431-4437 Thomas M, Narayan N, Pim D, Tomaic V, Massimi P, Nagasaka K, Kranjec C, Gammoh N, Banks L (2008) Human papillomaviruses, cervical cancer and cell polarity. Oncogene 27: 7018-7030 Tsai TC, Lee YL, Hsiao WC, Tsao YP, Chen SL (2005) NRIP, a novel nuclear receptor interaction protein, enhances the transcriptional activity of nuclear receptors. J Biol Chem 280: 20000-20009 Tu CL, Chang W, Bikle DD (2001) The extracellular calcium-sensing receptor is required for calcium-induced differentiation in human keratinocytes. J Biol Chem 276: 41079-41085 Vetter SW, Leclerc E (2003) Novel aspects of calmodulin target recognition and activation. Eur J Biochem 270: 404-414 Wang X, Naidu SR, Sverdrup F, Androphy EJ (2009) Tax1BP1 interacts with papillomavirus E2 and regulates E2-dependent transcription and stability. J Virol 83: 2274-2284 Wu MH, Chan JY, Liu PY, Liu ST, Huang SM (2007a) Human papillomavirus E2 protein associates with nuclear receptors to stimulate nuclear receptor- and E2-dependent transcriptional activations in human cervical carcinoma cells. Int J Biochem Cell Biol 39: 413-425 Wu MH, Huang CJ, Liu ST, Liu PY, Ho CL, Huang SM (2007b) Physical and functional interactions of human papillomavirus E2 protein with nuclear receptor coactivators. Biochem Biophys Res Commun 356: 523-528 Wu SY, Lee AY, Hou SY, Kemper JK, Erdjument-Bromage H, Tempst P, Chiang CM (2006) Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev 20: 2383-2396 Wysocka J, Swigut T, Milne TA, Dou Y, Zhang X, Burlingame AL, Roeder RG, Brivanlou AH, Allis CD (2005) WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121: 859-872 Yao JM, Breiding DE, Androphy EJ (1998) Functional interaction of the bovine papillomavirus E2 transactivation domain with TFIIB. J Virol 72: 1013-1019 You J, Croyle JL, Nishimura A, Ozato K, Howley PM (2004) Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 117: 349-360 Zheng G, Schweiger MR, Martinez-Noel G, Zheng L, Smith JA, Harper JW, Howley PM (2009) Brd4 regulation of papillomavirus protein E2 stability. J Virol 83: 8683-8692 zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2: 342-350 zur Hausen H (2009) Papillomaviruses in the causation of human cancers - a brief historical account. Virology 384: 260-265 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48118 | - |
| dc.description.abstract | 我們之前發現了一個基因命名為核受體交互作用蛋白(Nuclear receptor interaction protein, NRIP)，在質固醇受體(Glucocorticoid receptor, GR)及人類乳突瘤狀病毒(Human papillomavirus, HPV)的E2蛋白所驅動的基因表現上，其功能可作為一轉錄作用輔因子。我們闡述了NRIP為一個新的可以與人類乳突瘤狀病毒16型之E2結合蛋白，人類乳突瘤狀病毒16型的E2蛋白可以在生物體內、體外與NRIP直接形成一複合體，NRIP藉由其N端與E2蛋白的轉錄活化模組(Transactivation domain)相互作用，只有完整全長的NRIP可以穩定E2蛋白並誘導人類乳突瘤狀病毒的基因表現。利用兩種針對NRIP設計的小干擾RNA可以降低E2的表現及其所驅動的基因表現；我們另外發現在鈣離子存在的環境下，NRIP可透過它的IQ模組直接與攜鈣素(Calmodulin, CaM)結合導致E2的去泛素作用(Deubiquitination)及增加E2的蛋白質穩定性，由NRIP及攜鈣素所形成的複合體可以活化鈣調磷酸酶(Calcineurin, CaN)使得E2蛋白發生去磷酸化以及穩定性增加。我們呈現了E2蛋白在體內磷酸化的證據並且提出NRIP可以做為一個支架蛋白(scaffold protein)聚集E2及攜鈣素，導致E2蛋白發生去磷酸化及去泛素化進而增強蛋白質穩定性及其所驅動的基因表現。此外我們全面地評估NRIP在人類乳突瘤狀病毒16型基因表現上所扮演的角色。首先，我們發現了位於人類乳突瘤狀病毒16型啟動子上核酸7695至7710上新的質固醇受體結合位置(Glucocorticoid receptor response element, GRE)；接著，我們確立了在賀爾蒙的存在下，質固醇受體調控人類乳突瘤狀病毒基因表現上NRIP可作用為轉錄輔因子；在已發現人類乳突瘤狀病毒啟動子的四個質固醇受體接合位置上，NRIP只作用於第三位置。同時在沒有賀爾蒙存在下，NRIP可與E2病毒蛋白形成一複合體結合在人類乳突瘤狀病毒啟動子上的E2結合位置(E2 response element, E2E)來調控基因表現，並且在賀爾蒙存在下，NRIP可以與質固醇受體及E2病毒蛋白形成一個三蛋白複合體作用在啟動子上的質固醇結合位置而非E2結合位置上調控基因的表現。這些結果指出NRIP與質固醇受體同為E2蛋白的結合蛋白，並且在賀爾蒙存在或不存在下，NRIP在調控人類乳突瘤狀病毒基因表現上可分別透過啟動子上的質固醇受體結合位置或E2結合位置。 | zh_TW |
| dc.description.abstract | We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. We demonstrate that NRIP is a novel binding protein for human papillomavirus 16 (HPV-16) E2 protein. HPV-16 E2 and NRIP can directly associate into a complex in vivo and in vitro, and the N-terminal domain of NRIP interacts with the transactivation domain of HPV-16 E2. Only full-length NRIP can stabilize E2 protein and induce HPV gene expression, and NRIP silenced by two designed siRNAs decreases E2 protein levels and E2-driven gene expression. We found that NRIP can directly bind with calmodulin in the presence of calcium through its IQ domain, resulting in decreased E2 ubiquitination and increased E2 protein stability. Complex formation between NRIP and calcium/calmodulin activates the phosphatase calcineurin to dephosphorylate E2 and increase E2 protein stability. We present evidences for E2 phosphorylation in vivo, and show that NRIP acts as a scaffold to recruit E2 and calcium/calmodulin to prevent polyubiquitination and degradation of E2, enhancing E2 stability and E2-driven gene expression. Moreover, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. First, we identified a novel glucocorticoid response element (GRE4) located at nucleotides 7695 to 7710 of the HPV-16 promoter. We then determined that NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone, NRIP only located at the GRE3 site of the HPV promoter among four identified GRE sites. Additionally, NRIP can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively. | en |
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| dc.description.tableofcontents | 序言 ............................................................................................................................................. I
中文摘要 ................................................................................................................................... II ABSTRACT ............................................................................................................................. IV CHAPTER 1 INTRODUCTION ............................................................................................................ 1 2 MATERIAL AND METHODS ..................................................................................... 7 PLASMID CONSTRUCTION ....................................................................................................................... 7 CELL CULTURE ..................................................................................................................................... 9 TRANSFECTION AND LUCIFERASE ASSAY ................................................................................................. 9 IMMUNOPRECIPITATION AND WESTERN-BLOT ANALYSIS ......................................................................... 10 IN VITRO BINDING ASSAY ...................................................................................................................... 10 IMMUNOFLUORESCENT ASSAY .............................................................................................................. 11 CHROMATIN IMMUNOPRECIPITATION ASSAY .......................................................................................... 12 RNA EXTRACTION AND SEMI-QUANTITATIVE RT-PCR ANALYSIS ........................................................... 13 PHOS-TAG SDS-PAGE ......................................................................................................................... 14 3 RESULTS ......................................................................................................................... 16 PART ONE: NRIP, A NOVEL CALMODULIN BINDING PROTEIN, ACTIVATES CALCINEURIN TO DEPHOSPHORYLATE HPV E2 PROTEIN ................................................................................................ 16 NRIP interacts with papillomavirus E2 in vitro and in vivo ......................................................... 16 NRIP enhances E2-mediated transcription and colocalizes with E2 on HPV promoter ............... 17 The N-terminal domain of NRIP interacts with the transactivation domain of HPV-16 E2 ......... 20 NRIP increases E2 protein levels by preventing proteasomal degradation .................................. 22 The IQ domain of NRIP is responsible for CaM binding .............................................................. 25 The IQ domain of NRIP plays a functional role in NRIP coactivity and E2 stabilization ............. 27 NRIP prevents E2 degradation by blocking polyubiquitination and phosphorylation of HPV-16 E2 proteins in a CaM-dependent manner ..................................................................................... 29 PART TWO: NRIP ENHANCES HPV GENE EXPRESSION VIA INTERACTION WITH EITHER GR OR E2 ..... 33 Hormone activation of human papillomavirus gene expression ................................................... 33 Mapping of glucocorticoid response element-binding sequences in HPV-16 promoter that respond to GR ............................................................................................................................... 34 Effect of NRIP on GR-mediated HPV promoter activity ............................................................... 36 NRIP enhances HPV-16 promoter activity via binding to GR ...................................................... 37 NRIP activates HPV 16 gene expression via interaction with E2 and/or GR ............................... 38 Knockdown of NRIP reduces HPV-16 E6/E7 gene expression and results in inhibition of cell proliferation ................................................................................................................................. 41 4 DISCUSSION .................................................................................................................. 43 PART ONE: NRIP, A NOVEL CALMODULIN BINDING PROTEIN, ACTIVATES CALCINEURIN TO DEPHOSPHORYLATE HPV E2 PROTEIN ................................................................................................ 43 PART TWO: NRIP ENHANCES HPV GENE EXPRESSION VIA INTERACTION WITH EITHER GR OR E2 ..... 51 5 CONCLUSION ............................................................................................................... 56 6 REFERENCES ............................................................................................................... 57 FIGURES .......................................................................................................................... 67 NRIP INTERACTS WITH HPV E2 PROTEIN IN VITRO AND IN VIVO ......................................................... 68 NRIP COLOCALIZES WITH E2 ON HPV-16 PROMOTER AND ENHANCES E2-MEDIATED TRANSCRIPTIONAL ACTIVITY .............................................................................................................. 69 IDENTIFICATION OF DOMAINS REQUIRED FOR THE INTERACTION BETWEEN NRIP AND E2 ................. 71 NRIP STABILIZES HPV 16E2 BY PREVENTING ITS PROTEASOMAL DEGRADATION .............................. 73 NRIP BINDS CALMODULIN IN VITRO AND IN VIVO ................................................................................ 75 THE IQ DOMAIN OF NRIP IS REQUIRED FOR ITS COACTIVITY AND E2 STABILIZATION ........................ 76 NRIP BLOCKS THE POLYUBIQUITINATION AND PHOSPHORYLATION OF HPV-16 E2 THROUGH ITS CAM BINDING DOMAIN ............................................................................................................................... 77 MUTATIONAL ANALYSIS OF HPV-16 E2 PHOSPHORYLATION REGION ................................................ 79 GLUCOCORTICOID ACTIVATES HUMAN PAPILLOMAVIRUS GENE EXPRESSION ..................................... 80 A NOVEL FOURTH GLUCOCORTICOID RECEPTOR-BINDING SITE ON THE HUMAN PAPILLOMAVIRUS-16 LONG CONTROL REGION ...................................................................................................................... 81 NUCLEAR RECEPTOR-INTERACTION PROTEIN ENHANCES GLUCOCORTICOID RECEPTOR-MEDIATED HUMAN PAPILLOMAVIRUS-16 AND -18 PROMOTER ACTIVITY .............................................................. 82 GLUCOCORTICOID RECEPTOR AND NUCLEAR RECEPTOR-INTERACTION PROTEIN ARE COLOCALIZED AT THE HUMAN PAPILLOMAVIRUS-16 PROMOTER IN THE PRESENCE OF DEXAMETHASONE ...................... 83 NUCLEAR RECEPTOR-INTERACTION PROTEIN ACTS SYNERGISTICALLY WITH E2 AND THE GLUCOCORTICOID RECEPTOR .............................................................................................................. 85 KNOCKDOWN OF ENDOGENOUS NRIP RESULTS IN DECREASED MRNA EXPRESSION OF E6 AND E7 AND INHIBITS PROLIFERATION ACTIVATED BY DEXAMETHASONE .............................................................. 87 8 APPENDIX ...................................................................................................................... 88 | |
| dc.language.iso | en | |
| dc.subject | E2蛋白 | zh_TW |
| dc.subject | 核受質結合蛋白 | zh_TW |
| dc.subject | 人類乳突瘤狀病毒 | zh_TW |
| dc.subject | 質固醇受體 | zh_TW |
| dc.subject | HPV | en |
| dc.subject | E2 | en |
| dc.subject | GR | en |
| dc.subject | NRIP | en |
| dc.title | NRIP透過質固醇受體與E2病毒蛋白調控人類乳突瘤狀病毒的基因表現 | zh_TW |
| dc.title | NRIP Enhances HPV Gene Expression via Interaction with Either GR or E2 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 鄧述諄(Shu-Chun Teng),王萬波(Won-Bo Wang),葉秀慧(Shiou-Hwei Yeh),吳君泰(June-Tai Wu) | |
| dc.subject.keyword | 核受質結合蛋白,人類乳突瘤狀病毒,質固醇受體,E2蛋白, | zh_TW |
| dc.subject.keyword | NRIP,HPV,GR,E2, | en |
| dc.relation.page | 98 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-06-17 | |
| 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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