系統識別號 U0026-0501201014440500
論文名稱(中文) 利用定量奈米質譜學來解析與雌激素轉錄行為相關的蛋白質複合體
論文名稱(英文) Quantitative Nano-Proteomics for Protein Complexes (QNanoPX) Related to Estrogen Transcriptional Action
校院名稱 成功大學
系所名稱(中) 化學系碩博士班
系所名稱(英) Department of Chemistry
學年度 98
學期 1
出版年 99
研究生(中文) 鄭百喬
研究生(英文) Pai-Chiao Cheng
電子信箱 jinglejo0124@gmail.com
學號 l3892111
學位類別 博士
語文別 英文
論文頁數 73頁
口試委員 指導教授-陳淑慧
中文關鍵字 金奈米  親和性分離  蛋白質複合體  雌激素應答序列  定量質譜學  聚乙二醇  自組裝  膠體粒子  雌激素  雌激素接受器阿法  蛋白路徑 
英文關鍵字 protein complex  nanoparticle  immunoprecipitation  estrogen action  quantitative proteomics  stable isotope dimethyl labeling  estrogen receptor alpha  estrogen responsive element  estradiol 
中文摘要 我們發展了一套利用特殊化學修飾的金奈米粒子作為親和性分離細胞中大型蛋白質複合體的新穎探針。利用這項技術來全面性的標定出與雌激素應答序列相關的轉錄活化複合體,此方法命名為針對蛋白質複合體的定量奈米質譜學(QNanoPX)。此策略中我們將修飾上聚乙二醇以及雌激素應答序列的金奈米粒子當作正探針,而把只修飾上聚乙二醇而未修飾雌激素應答序列的金奈米粒子作為負探針,皆是利用硫醇自組裝單分子層的方法將分子與金奈米做共價鍵結。金奈米正探針有非常高的抵抗非專一性吸附蛋白的能力以及很高的分散性,且由實驗結果得知,它分離純化待測蛋白的能力比一般傳統使用的膠體粒子好二十倍。除此之外,金奈米粒子單純只用表面分子與待測物作用,所以可用來分離的蛋白複合體大小不會受限,不像膠體粒子是有孔徑的,因此太大的蛋白複合體會無法進入孔徑中作用,而且在分離過程一些雜蛋白也有可能會擴散進孔徑中被困住而造成過高的背景訊號。此親和性純化的方法同時結合了定量質譜學及統計學來揭露乳癌細胞內會與雌激素應答序列作用的蛋白複合體之組成、以及鑑定複合體中會受雌激素存在而調控的蛋白種類。結果顯示,被金奈米正探針純化下來的蛋白絕大多數都是透過有意義的作用力,而且包括雌激素接受器阿法在內的將近一半的蛋白當受到雌激素二十四小時刺激後會被些微的影響。將結果用生物資訊和路徑分析的方法剖析後發現,大多數受調控的蛋白不只受雌激素接受器阿法的轉錄調節、也跟c-Myc有關。進一步的研究證實,雌激素會使c-Myc和雌激素應答序列的作用力增強十四倍,這也代表c-Myc和雌激素接受器阿法在雌激素調控的轉錄行為中扮演著很重要的角色。總而言之,我們的研究結果證明了此針對蛋白質複合體的定量奈米質譜學方法可成功的應用在蛋白路徑的研究,也可進一步揭開轉錄因子相互作用的重要性。
英文摘要 We developed an integrated proteomics approach using a chemically functionalized gold nanoparticle (AuNP) as a novel probe for affinity purification in order to analyze a large protein complex in vivo. We then applied this approach to globally map the transcriptional activation complex of the estrogen response element (ERE). This approach was designated as Quantitative Nano-Proteomics for Protein complexes (QNanoPX). In this approach, the positive AuNP-ERE probes were functionalized with polyethylene glycol (PEG) and the consensus sequence of ERE and negative AuNP-PEG probes were functionalized with PEG without the ERE via thiolated self-assembly monolayer (SAM) technique. The AuNP-ERE probe had substantially low nonspecific binding and high solubility, which resulted in a 20-fold enrichment of the factor compared to gel beads. In addition, the surface-only binding allows the probe to capture a large protein complex without any restrictions due to pore size. The affinity purification method was combined with MS-based quantitative proteomics and statistical methods to reveal the components of the ERE complex in MCF-7 cells and to identify those components within the complex that were altered by the presence of 17-estradiol (E2). Results indicated that a majority of proteins pulled down by the positive probe exhibited significant binding, and approximately one-half of the proteins, including estrogen receptor  (ER), were slightly but significantly affected by a 24-h treatment with E2. Based on a combination of bioinformatic and pathway analysis, most of the affected proteins, however, appeared to be related to the transcriptional regulation of not only ER, but also c-Myc. Further confirmation indicated that E2 enhanced the ERE binding of c-Myc by 14-fold, which indicated that c-Myc may play a major role, along with ER, in E2-mediated transcription. Taken together, our results demonstrated a successful QNanoPX approach towards pathway discovery and further revealed the importance of cross-interactions among transcription factors.
論文目次 中文摘要 .............................................. I
Abstract ............................................. II
誌謝 .................................................. III
Table of Contents .................................... IV
List of Figures & Tables ............................. VI
Abbreviations ........................................ VIII

Chapter 1: Backgrounds and Introductions
1.1 Introduction of Estrogen Actions ................... 1
1.1.1 Estrogen Pathways ................................ 1
1.1.2 Estrogen Receptor ................................ 3
1.2 Quantitative Proteomics ............................ 9
1.3 Current Methods .................................... 13
1.4 Research Motivation and Goal ....................... 16

Chapter 2: Experimental Procedures
2.1 Materials and Methods .............................. 17
2.1.1 Materials ........................................ 17
2.1.2 Instruments ...................................... 17
2.2 Probe Fabrication .................................. 20
2.3 Cell Culture and Nuclear Extraction ................ 20
2.4 Affinity Purification Assay ........................ 21
2.5 Western Blotting Analysis .......................... 21
2.6 Trypsin Digestion and Dimethyl Labeling............. 22
2.7 nanoLC/MS Analysis ................................. 22
2.8 Biostatistics ...................................... 24

Chapter 3: Results
3.1 Au Nanoparticle Probes ............................. 25
3.1.1 Characterization ................................. 25
3.1.2 Parameter Optimization ........................... 28
3.2 Comparison between AuNP-ERE Probes and Gel Beads ... 31
3.3 Protein Identification and Quantification .......... 33
3.4 Bioinformatics Analysis of the ERE Protein Complex . 36
3.5 Relationship between ERα and c-Myc ................. 38

Chapter 4: Discussion
4.1 AuNP-ERE Probes for Affinity Pull-down ............. 40
4.2 Quantitative and Statistical Analysis .............. 41
4.3 ERα and c-Myc ...................................... 42
4.4 Conclusions ........................................ 44

Acknowledgements ....................................... 44
Appendix I ............................................. 45
Appendix II ............................................ 50
Appendix III ........................................... 53
References ............................................. 66
參考文獻 1. Behl, C.; Widmann, M.; Trapp, T.; Holsboer, F., 17-beta Estradiol Protects Neurons from Oxidative Stress-induced Cell-Death In Vitro. Biochem. Biophys. Res. Commun. 1995, 216 (2), 473-482.
2. Douma, S. L.; Husband, C.; O'Donnell, M. E.; Barwin, B. N.; Woodend, A. K., Estrogen-related mood disorders - Reproductive life cycle factors. Adv. Nurs. Sci. 2005, 28 (4), 364-375.
3. Lasiuk, G. C.; Hegadoren, K. M., The effects of estradiol on central serotonergic systems and its relationship to mood in women. Biol. Res. Nurs. 2007, 9 (2), 147-160.
4. Lorenzo, J., A new hypothesis for how sex steroid hormones regulate bone mass. J. Clin. Invest. 2003, 111 (11), 1641-1643.
5. Deroo, B. J.; Korach, K. S., Estrogen receptors and human disease. J. Clin. Invest. 2006, 116 (3), 561-570.
6. Santen, R. J.; Song, R. X.; Zhang, Z.; Kumar, R.; Jeng, M. H.; Masamura, S.; Yue, W.; Berstein, L., Adaptive hypersensitivity to estrogen: mechanism for superiority of aromatase inhibitors over selective estrogen receptor modulators for breast cancer treatment and prevention. (vol 10, pg 111, 2003). Endocr-Relat. Cancer 2003, 10 (3).
7. Lupu, R.; Menendez, J. A., Minireview: Targeting fatty acid synthase in breast and endometrial cancer: An alternative to selective estrogen receptor modulators? Endocrinology 2006, 147 (9), 4056-4066.
8. Malorni, L.; Cacace, G.; Cuccurullo, M.; Pocsfalvi, G.; Chambery, A.; Farina, A.; Di Maro, A.; Parente, A.; Malorni, A., Proteomic analysis of MCF-7 breast cancer cell line exposed to mitogenic concentration of 17 beta-estradiol. Proteomics 2006, 6 (22), 5973-5982.
9. Zhu, Z. Y.; Boobis, A. R.; Edwards, R. J., Identification of estrogen-responsive proteins in MCF-7 human breast cancer cells using label-free quantitative proteomics. Proteomics 2008, 8 (10), 1987-2005.
10. Pearce, S. T.; Jordan, V. C., The biological role of estrogen receptors alpha and beta in cancer. Crit. Rev. Oncol./Hematol. 2004, 50 (1), 3-22.
11. Koehler, K. F.; Helguero, L. A.; Haldosen, L. A.; Warner, M.; Gustafsson, J. A., Reflections on the discovery and significance of estrogen receptor beta. Endocr. Rev. 2005, 26 (3), 465-478.
12. Marabotti, A.; Colonna, G.; Facchiano, A., New computational strategy to analyze the interactions of ER alpha and ER beta with different ERE sequences. J. Comput. Chem. 2007, 28 (6), 1031-1041.
13. Moore, J. T.; Collins, J. L.; Pearce, K. H., The nuclear receptor superfamily and drug discovery. ChemMedChem 2006, 1 (5), 504-523.
14. Tzukerman, M. T.; Esty, A.; Santisomere, D.; Danielian, P.; Parker, M. G.; Stein, R. B.; Pike, J. W.; McDonnell, D. P., Human Estrogen-Receptor Transactivational Capacity is Determined by both Cellular and Promoter Context and Mediated by 2 Functionally Distinct Intramolecular Regions. Mol. Endocrinol. 1994, 8 (1), 21-30.
15. Delaunay, F.; Pettersson, K.; Tujague, M.; Gustafsson, J. A., Functional differences between the amino-terminal domains of estrogen receptors alpha and beta. Mol. Pharmacol. 2000, 58 (3), 584-590.
16. Benecke, A.; Chambon, P.; Gronemeyer, H., Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2. EMBO Rep. 2000, 1 (2), 151-157.
17. Brzozowski, A. M.; Pike, A. C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J. A.; Carlquist, M., Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997, 389 (6652), 753-758.
18. Hillisch, A.; Peters, O.; Kosemund, D.; Muller, G.; Walter, A.; Schneider, B.; Reddersen, G.; Elger, W.; Fritzemeier, K. H., Dissecting physiological roles of estrogen receptor alpha and beta with potent selective ligands from structure-based design. Mol. Endocrinol. 2004, 18 (7), 1599-1609.
19. Fukuzawa, K.; Mochizuki, Y.; Tanaka, S.; Kitaura, K.; Nakano, T., Molecular interactions between estrogen receptor and its ligand studied by the ab initio fragment molecular orbital method. J. Phys. Chem. B 2006, 110 (32), 16102-16110.
20. Vega, V. B.; Lin, C. Y.; Lai, K. S.; Kong, S. L.; Xie, M.; Su, X. D.; Teh, H. F.; Thomsen, J. S.; Yeo, A. L.; Sung, W. K.; Bourque, G.; Liu, E. T., Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites. Genome Biol. 2006, 7 (9), 13.
21. Ruff, M.; Gangloff, M.; Wurtz, J. M.; Moras, D., Estrogen receptor transcription and transactivation Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors. Breast Cancer Res. 2000, 2 (5), 353-359.
22. Gewirth, D. T.; Sigler, P. B., The Basis for Half-site Specificity Explored Through a Noncognate Steroid Receptor-DNA Complex. Nat. Struct. Biol. 1995, 2 (5), 386-394.
23. Iliuk, A.; Galan, J.; Tao, W. A., Playing tag with quantitative proteomics. Anal. Bioanal. Chem. 2009, 393 (2), 503-513.
24. Wilm, M., Quantitative proteomics in biological research. Proteomics 2009, 9 (20), 4590-4605.
25. Karas, M.; Hillenkamp, F., Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10000 Daltons. Anal. Chem. 1988, 60 (20), 2299-2301.
26. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M., Electrospray Ionization for Mass-Spectrometry of Large Biomolecules. Science 1989, 246 (4926), 64-71.
27. Huber, L. A., Is proteomics heading in the wrong direction? Nat. Rev. Mol. Cell Biol. 2003, 4 (1), 74-80.
28. Gingras, A. C.; Gstaiger, M.; Raught, B.; Aebersold, R., Analysis of protein complexes using mass spectrometry. Nat. Rev. Mol. Cell Biol. 2007, 8 (8), 645-654.
29. Hsu, J. L.; Huang, S. Y.; Chow, N. H.; Chen, S. H., Stable-isotope dimethyl labeling for quantitative proteomics. Anal. Chem. 2003, 75 (24), 6843-6852.
30. Ong, S. E.; Mann, M., Mass spectrometry-based proteomics turns quantitative. Nat. Chem. Biol. 2005, 1 (5), 252-262.
31. Boersema, P. J.; Aye, T. T.; van Veen, T. A. B.; Heck, A. J. R.; Mohammed, S., Triplex protein quantification based on stable isotope labeling by peptide dimethylation applied to cell and tissue lysates. Proteomics 2008, 8 (22), 4624-4632.
32. Liao, L. J.; Park, S. K.; Xu, T.; Vanderklish, P.; Yates, J. R., Quantitative proteomic analysis of primary neurons reveals diverse changes in synaptic protein content in fmr1 knockout mice. P. Natl. Acad. Sci. USA 2008, 105 (40), 15281-15286.
33. Wepf, A.; Glatter, T.; Schmidt, A.; Aebersold, R.; Gstaiger, M., Quantitative interaction proteomics using mass spectrometry. Nat. Methods 2009, 6 (3), 203-205.
34. Schulze, W. X.; Mann, M., A novel proteomic screen for peptide-protein interactions. J. Biol. Chem. 2004, 279 (11), 10756-10764.
35. Guerrero, C.; Tagwerker, C.; Kaiser, P.; Huang, L., An integrated mass spectrometry-based proteomic approach - Quantitative analysis of tandem affinity-purified in vivo cross-linked protein complexes (QTAX) to decipher the 26 S proteasome-interacting network. Mol. Cell. Proteomics 2006, 5 (2), 366-378.
36. Phizicky, E. M.; Fields, S., Protein-protein Interactions - Methods for Detection and Analysis. Microbiol. Rev. 1995, 59 (1), 94-123.
37. Alber, F.; Dokudovskaya, S.; Veenhoff, L. M.; Zhang, W. H.; Kipper, J.; Devos, D.; Suprapto, A.; Karni-Schmidt, O.; Williams, R.; Chait, B. T.; Sali, A.; Rout, M. P., The molecular architecture of the nuclear pore complex. Nature 2007, 450 (7170), 695-701.
38. Pernodet, N.; Maaloum, M.; Tinland, B., Pore size of agarose gels by atomic force microscopy. Electrophoresis 1997, 18 (1), 55-58.
39. Cristea, I. M.; Williams, R.; Chait, B. T.; Rout, M. P., Fluorescent Proteins as Proteomic Probes. Mol. Cell. Proteomics 2005, 4 (12), 1933-1941.
40. Baron, R.; Willner, B.; Willner, I., Biomolecule-nanoparticle hybrids as functional units for nanobiotechnology. Chem. Commun. 2007, (4), 323-332.
41. Thaxton, C. S.; Georganopoulou, D. G.; Mirkin, C. A., Gold nanoparticle probes for the detection of nucleic acid targets. Clin. Chim. Acta 2006, 363 (1-2), 120-126.
42. Aubin-Tam, M. E.; Hamad-Schifferli, K., Structure and function of nanoparticle-protein conjugates. Biomed. Mater. 2008, 3 (3), 1-17.
43. Zhu, Z. J.; Rotello, V. M.; Vachet, R. W., Engineered nanoparticle surfaces for improved mass spectrometric analyses. Analyst 2009, 134 (11), 2183-2188.
44. Lin, H. Y.; Chen, C. T.; Chen, Y. C., Detection of phosphopeptides by localized surface plasma resonance of titania-coated gold nanoparticles immobilized on glass substrates. Anal. Chem. 2006, 78 (19), 6873-6878.
45. Teng, C. H.; Ho, K. C.; Lin, Y. S.; Chen, Y. C., Gold nanoparticles as selective and concentrating probes for samples in MALDI MS analysis. Anal. Chem. 2004, 76 (15), 4337-4342.
46. Nagahori, N.; Nishimura, S. I., Direct and efficient monitoring of glycosyltransferase reactions on gold colloidal nanoparticles by using mass spectrometry. Chem.-Eur. J. 2006, 12 (25), 6478-6485.
47. Chen, Y. J.; Chen, S. H.; Chien, Y. Y.; Chang, Y. W.; Liao, H. K.; Chang, C. Y.; Jan, M. D.; Wang, K. T.; Lin, C. C., Carbohydrate-encapsulated gold nanoparticles for rapid target-protein identification and binding-epitope mapping. Chembiochem 2005, 6 (7), 1169-1173.
48. Zhu, Z. J.; Ghosh, P. S.; Miranda, O. R.; Vachet, R. W.; Rotello, V. M., Multiplexed Screening of Cellular Uptake of Gold Nanoparticles Using Laser Desorption/Ionization Mass Spectrometry. J. Am. Chem. Soc. 2008, 130 (43), 14139-14143.
49. Hsu, J. L.; Huang, S. Y.; Shiea, J. T.; Huang, W. Y.; Chen, S. H., Beyond quantitative proteomics: Signal enhancement of the a(1) ion as a mass tag for peptide sequencing using dimethyl labeling. J. Proteome Res. 2005, 4 (1), 101-108.
50. Hsu, J. L.; Huang, S. Y.; Chen, S. H., Dimethyl multiplexed labeling combined with microcolumn separation and MS analysis for time course study in proteomics. Electrophoresis 2006, 27 (18), 3652-3660.
51. Champness, P. E., Electron Diffraction in the Transmission Electron Microscope. 2001.
52. Frisken, B. J., Revisiting the method of cumulants for the analysis of dynamic light-scattering data. Appl. Optics 2001, 40 (24), 4087-4091.
53. Marconi, U. M. B.; Puglisi, A.; Rondoni, L.; Vulpiani, A., Fluctuation-dissipation: Response theory in statistical physics. Phys. Rep.-Rev. Sec. Phys. Lett. 2008, 461 (4-6), 111-195.
54. Frens, G., Controlled Nucleation for Regulation of Particle-Size in Monodisperse Gold Suspensions. Nat.-Phys. Sci. 1973, 241 (105), 20-22.
55. Grabar, K. C.; Freeman, R. G.; Hommer, M. B.; Natan, M. J., Preparation and Characterization of Au Colloid Monolayers. Anal. Chem. 1995, 67 (4), 735-743.
56. Harris, D. C., Quantitative Chemical Analysis, 7th Edition, W. H. Freeman and Company. 61.
57. Cho, W. S.; Cho, M. J.; Jeong, J.; Choi, M.; Cho, H. Y.; Han, B. S.; Kim, S. H.; Kim, H. O.; Lim, Y. T.; Chung, B. H., Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. Toxicol. Appl. Pharmacol. 2009, 236 (1), 16-24.
58. Tkachenko, A. G.; Xie, H.; Coleman, D.; Glomm, W.; Ryan, J.; Anderson, M. F.; Franzen, S.; Feldheim, D. L., Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. J. Am. Chem. Soc. 2003, 125 (16), 4700-4701.
59. Cheng, A. S. L.; Jin, V. X.; Fan, M. Y.; Smith, L. T.; Liyanarachchi, S.; Yan, P. S.; Leu, Y. W.; Chan, M. W. Y.; Plass, C.; Nephew, K. P.; Davuluri, R. V.; Huang, T. H. M., Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters. Mol. Cell 2006, 21 (3), 393-404.
60. Wang, A.; Wu, C. J.; Chen, S. H., Gold nanoparticle-assisted protein enrichment and electroelution for biological samples containing low protein concentrations - A prelude of gel electrophoresis. J. Proteome Res. 2006, 5 (6), 1488-1492.
61. Weisz, A.; Rosales, R., Identification of an estrogen response element upstream of the human c-Fos gene that binds the estrogen-receptor and the AP-1 transcription factor. Nucleic Acids Res. 1990, 18 (17), 5097-5106.
62. Reha, D.; Kabelac, M.; Ryjacek, F.; Sponer, J.; Sponer, J. E.; Elstner, M.; Suhai, S.; Hobza, P., Intercalators. 1. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4 ',6-diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study. J. Am. Chem. Soc. 2002, 124 (13), 3366-3376.
63. Lin, C. Y.; Vega, V. B.; Thomsen, J. S.; Zhang, T.; Kong, S. L.; Xie, M.; Chiu, K. P.; Lipovich, L.; Barnett, D. H.; Stossi, F.; Yeo, A.; George, J.; Kuznetsov, V. A.; Lee, Y. K.; Charn, T. H.; Palanisamy, N.; Miller, L. D.; Cheung, E.; Katzenellenbogen, B. S.; Ruan, Y.; Bourque, G.; Wei, C. L.; Liu, E. T., Whole-genome cartography of estrogen receptor alpha binding sites. Plos Genet. 2007, 3 (6), 867-885.
64. Mani, K. M.; Lefebvre, C.; Wang, K.; Lim, W. K.; Basso, K.; Dalla-Favera, R.; Califano, A., A systems biology approach to prediction of oncogenes and molecular perturbation targets in B-cell lymphomas. Mol. Syst. Biol. 2008, 4.
65. Kininis, M.; Chen, B. S.; Diehl, A. G.; Isaacs, G. D.; Zhang, T.; Siepel, A. C.; Clark, A. G.; Kraus, W. L., Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters. Mol. Cell. Biol. 2007, 27 (14), 5090-5104.
66. Chen, Y. L.; Blackwell, T. W.; Chen, J.; Gao, J.; Lee, A. W.; States, D. J., Integration of genome and chromatin structure with gene expression profiles to predict c-MYC recognition site binding and function. Plos Comput. Biol. 2007, 3 (4), 602-615.
67. Chen, X.; Xu, H.; Yuan, P.; Fang, F.; Huss, M.; Vega, V. B.; Wong, E.; Orlov, Y. L.; Zhang, W. W.; Jiang, J. M.; Loh, Y. H.; Yeo, H. C.; Yeo, Z. X.; Narang, V.; Govindarajan, K. R.; Leong, B.; Shahab, A.; Ruan, Y. J.; Bourque, G.; Sung, W. K.; Clarke, N. D.; Wei, C. L.; Ng, H. H., Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 2008, 133 (6), 1106-1117.
68. Palomero, T.; Lim, W. K.; Odom, D. T.; Sulis, M. L.; Real, P. J.; Margolin, A.; Barnes, K. C.; O'Neil, J.; Neuberg, D.; Weng, A. P.; Aster, J. C.; Sigaux, F.; Soulier, J.; Look, A. T.; Young, R. A.; Califano, A.; Ferrando, A. A., NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. P. Natl. Acad. Sci. USA 2006, 103 (48), 18261-18266.
69. Margolin, A. A.; Palomero, T.; Sumazin, P.; Califano, A.; Ferrando, A. A.; Stolovitzky, G., ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes. P. Natl. Acad. Sci. USA 2009, 106 (1), 244-249.
70. Koch, H. B.; Zhang, R.; Verdoodt, B.; Bailey, A.; Zhang, C. D.; Yates, J. R.; Menssen, A.; Hermeking, H., Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach. Cell Cycle 2007, 6 (2), 205-217.
71. Li, Z. R.; Van Calcar, S.; Qu, C. X.; Cavenee, W. K.; Zhang, M. Q.; Ren, B., A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. P. Natl. Acad. Sci. USA 2003, 100 (14), 8164-8169.
72. Drouin, R.; Angers, M.; Dallaire, N.; Rose, T. M.; Khandjian, E. W.; Rousseau, F., Structural and functional characterization of the human FMR1 promoter reveals similarities with the hnRNP-A2 promoter region. Hum. Mol. Genet. 1997, 6 (12), 2051-2060.
73. Zeller, K. I.; Zhao, X. D.; Lee, C. W. H.; Chiu, K. P.; Yao, F.; Yustein, J. T.; Ooi, H. S.; Orlov, Y. L.; Shahab, A.; Yong, H. C.; Fu, Y. T.; Weng, Z. P.; Kuznetsov, V. A.; Sung, W. K.; Ruan, Y. J.; Dang, C. V.; Wei, C. L., Global mapping of c-Myc binding sites and target gene networks in human B cells. P. Natl. Acad. Sci. USA 2006, 103 (47), 17834-17839.
74. Sridharan, R.; Tchieu, J.; Mason, M. J.; Yachechko, R.; Kuoy, E.; Horvath, S.; Zhou, Q.; Plath, K., Role of the Murine Reprogramming Factors in the Induction of Pluripotency. Cell 2009, 136 (2), 364-377.
75. Reymann, S.; Borlak, J., Transcription profiling of lung adenocarcinomas of c-myc-transgenic mice: Identification of the c-myc regulatory gene network. Bmc Syst. Biol. 2008, 2.
76. Kim, J. W.; Chu, J. L.; Shen, X. H.; Wang, J. L.; Orkin, S. H., An extended transcriptional network for pluripotency of embryonic stem cells. Cell 2008, 132 (6), 1049-1061.
77. Gao, H.; Falt, S.; Sandelin, A.; Gustafsson, J. A.; Dahlman-Wright, K., Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver. Mol. Endocrinol. 2008, 22 (1), 10-22.
78. Blanchette, M.; Bataille, A. R.; Chen, X. Y.; Poitras, C.; Laganiere, J.; Lefebvre, C.; Deblois, G.; Giguere, V.; Ferretti, V.; Bergeron, D.; Coulombe, B.; Robert, F. O., Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression. Genome Res. 2006, 16 (5), 656-668.
79. Jin, V. X.; Leu, Y. W.; Liyanarachchi, S.; Sun, H.; Fan, M.; Nephew, K. P.; Huang, T. H. M.; Davuluri, R. V., Identifying estrogen receptor alpha target genes using integrated computational genomics and chromatin immunoprecipitation microarray. Nucleic Acids Res. 2004, 32 (22), 6627-6635.
80. Fernandez, P. C.; Frank, S. R.; Wang, L. Q.; Schroeder, M.; Liu, S. X.; Greene, J.; Cocito, A.; Amati, B., Genomic targets of the human c-Myc protein. Gene. Dev. 2003, 17 (9), 1115-1129.
81. Zeller, K. I.; Jegga, A. G.; Aronow, B. J.; O'Donnell, K. A.; Dang, C. V., An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol. 2003, 4 (10).
82. Dai, M. S.; Lu, H., Crosstalk Between c-Myc and Ribosome in Ribosomal Biogenesis and Cancer. J. Cell. Biochem. 2008, 105 (3), 670-677.
83. Kim, J.; Lee, J.; Lyer, V. R., Global Identification of Myc Target Genes Reveals Its Direct Role in Mitochondrial Biogenesis and Its E-Box Usage In Vivo. PLoS One 2008, 3 (3), e1798.
84. Park, J.; Wood, M. A.; Cole, M. D., BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation. Mol. Cell. Biol. 2002, 22 (5), 1307-1316.
85. Ogawa, S.; Oishi, H.; Mezaki, Y.; Kouzu-Fujita, M.; Matsuyama, R.; Nakagomi, M.; Mori, E.; Murayama, E.; Nagasawa, H.; Kitagawa, H.; Yanagisawa, J.; Yano, T.; Kato, S., Repressive domain of unliganded human estrogen receptor alpha associates with Hsc70. Genes Cells 2005, 10 (12), 1095-1102.
86. Aumais, J. P.; Lee, H. S.; Lin, R.; White, J. H., Selective interaction of hsp90 with an estrogen receptor ligand-binding domain containing a point mutation. J. Biol. Chem. 1997, 272 (18), 12229-12235.
87. Bouhouche-Chatelier, H.; Chadli, A.; Catelli, M. G., The N-terminal adenosine triphosphate binding domain of Hsp90 is necessary and sufficient for interaction with estrogen receptor. Cell Stress Chaperon. 2001, 6 (4), 297-305.
88. Denger, S.; Bahr-Ivacevic, T.; Brand, H.; Reid, G.; Blake, J.; Seifert, M.; Lin, C. Y.; May, K.; Benes, V.; Liu, E. T.; Gannon, F., Transcriptome profiling of estrogen-regulated genes in human primary osteoblasts reveals an osteoblast-specific regulation of the insulin-like growth factor binding protein 4 gene. Mol. Endocrinol. 2008, 22 (2), 361-379.
89. Ewing, R. M.; Chu, P.; Elisma, F.; Li, H.; Taylor, P.; Climie, S.; McBroom-Cerajewski, L.; Robinson, M. D.; O'Connor, L.; Li, M.; Taylor, R.; Dharsee, M.; Ho, Y.; Heilbut, A.; Moore, L.; Zhang, S.; Ornatsky, O.; Bukhman, Y. V.; Ethier, M.; Sheng, Y.; Vasilescu, J.; Abu-Farha, M.; Lambert, J. P.; Duewel, H. S.; Stewart, II; Kuehl, B.; Hogue, K.; Colwill, K.; Gladwish, K.; Muskat, B.; Kinach, R.; Adams, S. L.; Moran, M. F.; Morin, G. B.; Topaloglou, T.; Figeys, D., Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol. Syst. Biol. 2007, 3.
90. He, B.; Feng, Q.; Mukherjee, A.; Lonard, D. M.; DeMayo, F. J.; Katzenellenbogen, B. S.; Lydon, J. P.; O'Malley, B. W., A repressive role for prohibitin in estrogen signaling. Mol. Endocrinol. 2008, 22 (2), 344-360.
91. O'Connell, B. C.; Cheung, A. F.; Simkevich, C. P.; Tam, W.; Ren, X. J.; Mateyak, M. K.; Sedivy, J. M., A large scale genetic analysis of c-Myc-regulated gene expression patterns. J. Biol. Chem. 2003, 278 (14), 12563-12573.
92. Carroll, J. S.; Meyer, C. A.; Song, J.; Li, W.; Geistlinger, T. R.; Eeckhoute, J.; Brodsky, A. S.; Keeton, E. K.; Fertuck, K. C.; Hall, G. F.; Wang, Q. B.; Bekiranov, S.; Sementchenko, V.; Fox, E. A.; Silver, P. A.; Gingeras, T. R.; Liu, X. S.; Brown, M., Genome-wide analysis of estrogen receptor binding sites. Nat. Genet. 2006, 38 (11), 1289-1297.
93. Azuma, K.; Horie, K.; Inoue, S.; Ouchi, Y.; Sakai, R., Analysis of estrogen receptor alpha signaling complex at the plasma membrane. Febs Lett. 2004, 577 (3), 339-344.
94. Garrod, D.; Chidgey, M., Desmosome structure, composition and function. BBA-Biomembranes 2008, 1778 (3), 572-587.
95. Friend, K.; Lovejoy, A. F.; Steitz, J. A., U2 snRNP binds intronless histone pre-mRNAs to facilitate U7-snRN-dependent 3 ' end formation. Mol. Cell 2007, 28 (2), 240-252.
96. Meng, X. B.; Krokhin, O.; Cheng, K. D.; Ens, W.; Wilkins, J. A., Characterization of IQGAP1-containing complexes in NK-like cells: Evidence for Rac 2 and RACK1 association during homotypic adhesion. J. Proteome Res. 2007, 6 (2), 744-750.
97. Rual, J. F.; Venkatesan, K.; Hao, T.; Hirozane-Kishikawa, T.; Dricot, A.; Li, N.; Berriz, G. F.; Gibbons, F. D.; Dreze, M.; Ayivi-Guedehoussou, N.; Klitgord, N.; Simon, C.; Boxem, M.; Milstein, S.; Rosenberg, J.; Goldberg, D. S.; Zhang, L. V.; Wong, S. L.; Franklin, G.; Li, S. M.; Albala, J. S.; Lim, J. H.; Fraughton, C.; Llamosas, E.; Cevik, S.; Bex, C.; Lamesch, P.; Sikorski, R. S.; Vandenhaute, J.; Zoghbi, H. Y.; Smolyar, A.; Bosak, S.; Sequerra, R.; Doucette-Stamm, L.; Cusick, M. E.; Hill, D. E.; Roth, F. P.; Vidal, M., Towards a proteome-scale map of the human protein-protein interaction network. Nature 2005, 437 (7062), 1173-1178.
98. Bouwmeester, T.; Bauch, A.; Ruffner, H.; Angrand, P. O.; Bergamini, G.; Croughton, K.; Cruciat, C.; Eberhard, D.; Gagneur, J.; Ghidelli, S.; Hopf, C.; Huhse, B.; Mangano, R.; Michon, A. M.; Schirle, M.; Schlegl, J.; Schwab, M.; Stein, M. A.; Bauer, A.; Casari, G.; Drewes, G.; Gavin, A. C.; Jackson, D. B.; Joberty, G.; Neubauer, G.; Rick, J.; Kuster, B.; Superti-Furga, G., A physical and functional map of the human TNF-alpha NF-kappa B signal transduction pathway. Nat. Cell Biol. 2004, 6 (2), 97-105.
99. Jeong, H. W.; Li, Z.; Brown, M. D.; Sacks, D. B., IQGAP1 binds Rap1 and modulates its activity. J. Biol. Chem. 2007, 282 (28), 20752-20762.
100. Meek, S. E. M.; Lane, W. S.; Piwnica-Worms, H., Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. J. Biol. Chem. 2004, 279 (31), 32046-32054.
101. Vladimirova, N. M.; Murav'eva, T. I.; Ovchinnikova, T. V.; Potapenko, N. A.; Khodova, O. M., Na+,K+-ATPase isozymes in the bovine brain grey matter and stem. Biol. Membrany 1998, 15 (3), 349-352.
102. Alexandru, G.; Graumann, J.; Smith, G. T.; Kolawa, N. J.; Fang, R. H.; Deshaies, R. J., UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1 alpha turnover. Cell 2008, 134 (5), 804-816.
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