跳到主要內容

臺灣博碩士論文加值系統

(34.204.180.223) 您好!臺灣時間:2021/07/31 17:40
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:張曉婷
研究生(外文):Siao-Ting Chong
論文名稱:藉由定量磷酸化蛋白質體學分析探討MCM2在肺癌細胞中的調控網絡
論文名稱(外文):Quantitative phosphoproteomic analysis uncovers the regulatory networks of minichromosome maintenance protein 2 in lung cancer cells
指導教授:阮雪芬阮雪芬引用關係
指導教授(外文):Hsueh-Fen Juan
口試委員:黃宣誠王憶卿李岳倫陳頌方
口試委員(外文):Hsuan-Cheng HuangWang, Yi-ChingYueh-Luen LeeSung-Fang Chen
口試日期:2015-07-28
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:分子與細胞生物學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:81
中文關鍵詞:定量磷酸化蛋白質體學微小染色體維持蛋白2調控網絡肺癌
外文關鍵詞:Quantitative phosphoproteomeminichromosome maintenance protein-2regulatory networkslung cancer cells
相關次數:
  • 被引用被引用:0
  • 點閱點閱:142
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
微小染色體維持蛋白2(MCM2)是DNA複製的主要調控因子。 MCM2與其它MCM蛋白結合形成六聚體複合物(MCM2-7),並發揮具有解旋酶活性的功能。其功能除了用於DNA解旋,還會限制DNA在每個細胞週期僅複製一次。 MCM2在增殖細胞中表現量高,因此在許多種癌症被廣泛用作生物標誌物。然而,MCM2的分子調控機制在肺癌細胞中研究甚少。在這項研究中,我們用A549 (wild-type p53)和H1299(p53-null)細胞株探討MCM2在肺腺癌扮演的角色。研究結果顯示,在A549細胞中過表達MCM2會促進細胞增殖,而在H1299細胞中抑制MCM2表達則會減少細胞增殖。接著,我們進行定量磷酸化蛋白質體學來揭示在肺癌細胞中受MCM2調控的重要下游基因的網絡。我們在過度表達MCM2的A549細胞中共鑑定出594個磷酸化蛋白及1494個磷酸化位點。這些磷酸化位點中,有164磷酸化蛋白具有顯著差異。此外,在低表達MCM2的H1299細胞中,我們鑑定588個磷酸化蛋白及1599個磷酸化位點。這些磷酸化位點中,有82個磷酸化蛋白有顯著差異。這些有顯著差異的磷酸化蛋白參與了RNA剪接,細胞週期和細胞骨架等功能。在表達MCM2的A549細胞過和低表達MCM2的H1299細胞中,我們發現一個共同被調控的磷酸化位點,即是絲氨酸-99(Ser99),它位在高遷移率族蛋白HMG-Ⅰ/ HMG -Y(HMGA1)上。這表明HMGA1-Ser99對肺癌細胞有著重要的調節作用。我們的結果提供肺癌細胞受MCM2調控的磷酸化蛋白質體,並發現其調控磷酸化網絡。這些研究為肺癌治療提供了新的目標。

Minichromosome maintenance protein 2 (MCM2) is a licensing factor for DNA replication. It interacts with other MCM proteins to comprise MCM2-7 complex, which acts as a helicase for DNA unwinding and limits DNA replication to one round per cell cycle. MCM2 has been widely used as a biomarker for proliferation in many types of cancer. However, the molecular regulation underlying MCM2 in lung cancer cells is poorly understood. In this study, we investigated the role of MCM2 in lung adenocarcinoma A549 (wild-type p53) and H1299 (null p53) cells. MCM2 overexpression increased cell proliferation in A549 cells while silencing MCM2 decreased cell proliferation in H1299 cells. We performed global quantitative phosphoproteomic analysis to uncover the important downstream networks regulated by MCM2 in lung cancer cells. We identified 1484 phosphorylation sites in 593 phosphoproteins of MCM2-overexpressed A549 cells. Of these phosphosites, 110 phosphoproteins were significantly changed in response to MCM2 overexpression. In addition, we identified 1599 phosphorylation sites in 592 phosphoproteins of MCM2-silenced H1299 cells. Of these phosphosites, 57 phosphoproteins were significantly changed in response to MCM2 silencing. The differentially regulated phosphoproteins are involved in biological functions such as RNA splicing, cell cycle and cytoskeleton regulation. Functional study demonstrated that MCM2 overexpression promoted cell migration in A549 cells. Moreover, silencing MCM2 inhibits cell migration and induces cell cycle arrest in H1299 cells. Furthermore, we observed a common phosphorylation change at Ser-99 of high mobility group protein HMG-I/HMG-Y (HMGA1) in both MCM2 overexpression and silencing, indicating an important regulatory effect of Ser-99 HMGA1 on lung cancer cells. The phosphoproteomic profiling of MCM2 in lung cancer cells provides new insight about phosphorylation networks regulated by MCM2 and reveals novel targets for lung cancer therapy.

Contents
口試委員會審定書 I
誌謝 II
中文摘要 III
ABSTRACT IV
LIST OF FIGURES IX
LIST OF TABLES XI
Chapter 1 INTRODUCTION 1
1.1 Lung cancer 1
1.2 Minichromosome maintenance protein 2 (MCM2) 1
1.3 The MCM2 and cancer 2
1.4 Phosphoproteomics 2
1.4 Aim of the study 4
1.5 Experimental Design 4
Chapter 2 EXPERIMENTAL PROCESSES 6
2.1 Cell Culture human lung epithelial cells 6
2.2 Protein extraction 6
2.3 Reduction, Alkylation and Protein Digestion 7
2.4 Dimethyl labelling 7
2.5 Phosphopeptide Enrichment 8
2.6 NanoLC−MS/MS Analysis 8
2.7 Data Processing and Analyses 9
2.8 Plasmid construction and transfection 10
2.9 siRNA transfection 10
2.10 Site-directed mutagenesis 11
2.11 MTT and MTS cell viability assay 11
2.12 Colony formation assay 12
2.13 Cell migration assay 12
2.14 Cell cycle analysis using flow cytometry 12
2.15 Western blot 13
2.16 Statistics analysis 14
Chapter3 RESULTS 15
3.1 Overexpression of MCM2 in A549 increased cell proliferation and silencing MCM2 in H1299 cells decreased cell proliferation 15
3.2 P53 might be the up-regulator of MCM2 16
3.3 Phosphoproteome of MCM2 overexpression in A549 cells and silencing MCM2 in H1299 cells 16
3.4 Identification of differentially regulated phosphoproteins in response to MCM2 18
3.5 Overlap between phosphoproteome of MCM2 overxepression and silencing MCM2 18
3.6 Functional annotation of MCM2-regulated phosphoproteins 19
3.7 Overexpression of MCM2 in A549 increased cell migration while silencing MCM2 in H1299 cells decreased cell migration 20
3.8 Silencing MCM2 in H1299 cells induced cell cycle arrest 20
3.9 Phosphorylation of HMGA1 at Ser99 is essential for viability 21
Chapter 4 DISCUSSION 23
Chapter 5 CONCLUSION 28
Chapter 6 FUTURE WORK 29
ABBREVIATION 30
REFERENCES 32
FIGURES.. 41
TABLES 61


(1) Siegel, R.; Ma, J.; Zou, Z.; Jemal, A., Cancer statistics, 2014. CA Cancer J. Clin. 2014, 64 (1), 9-29.
(2) Wang, B. Y.; Huang, J. Y.; Cheng, C. Y.; Lin, C. H.; Ko, J. L.; Liaw, Y. P., Lung Cancer and Prognosis in Taiwan: A Population-Based Cancer Registry. J. Thorac. Oncol. 2013, 8 (9), 1128-1135.
(3) Minna, J. D.; Roth, J. A.; Gazdar, A. F., Focus on lung cancer. Cancer Cell 2002, 1 (1), 49-52.
(4) Evrin, C.; Clarke, P.; Zech, J.; Lurz, R.; Sun, J.; Uhle, S.; Li, H.; Stillman, B.; Speck, C., A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc. Natl. Acad. Sci. U S A 2009, 106 (48), 20240-20245.
(5) Remus, D.; Beuron, F.; Tolun, G.; Griffith, J. D.; Morris, E. P.; Diffley, J. F., Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell 2009, 139 (4), 719-730.
(6) Gambus, A.; Jones, R. C.; Sanchez-Diaz, A.; Kanemaki, M.; van Deursen, F.; Edmondson, R. D.; Labib, K., GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat. Cell Biol. 2006, 8 (4), 358-366.
(7) Ilves, I.; Petojevic, T.; Pesavento, J. J.; Botchan, M. R., Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins. Mol. Cell 2010, 37 (2), 247-258.
(8) Moyer, S. E.; Lewis, P. W.; Botchan, M. R., Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc. Natl. Acad. Sci. U S A 2006, 103 (27), 10236-10241.
(9) Lei, M.; Tye, B. K., Initiating DNA synthesis: from recruiting to activating the MCM complex. J. Cell Sci. 2001, 114 (8), 1447-1454.
(10) Kearsey, S. E.; Maiorano, D.; Holmes, E. C.; Todorov, I. T., The role of MCM proteins in the cell cycle control of genome duplication. Bioessays 1996, 18 (3), 183-190.
(11) Burger, M., MCM2 and MCM5 as Prognostic Markers in Colon Cancer: A Worthwhile Approach. Dig. Dis. Sci. 2009, 54 (2), 197-198.
(12) Liu, M.; Li, J. S.; Tian, D. P.; Huang, B.; Rosqvist, S.; Su, M., MCM2 expression levels predict diagnosis and prognosis in gastric cardiac cancer. Histol. Histopathol. 2013, 28 (4), 481-492.
(13) Wojnar, A.; Kobierzycki, C.; Krolicka, A.; Pula, B.; Podhorska-Okolow, M.; Dziegiel, P., Correlation of Ki-67 and MCM-2 proliferative marker expression with grade of histological malignancy (G) in ductal breast cancers. Folia Histochem. Cytobiol. 2010, 48 (3), 442-446.
(14) Meng, M. V.; Grossfeld, G. D.; Williams, G. H.; Dilworth, S.; Stoeber, K.; Mulley, T. W.; Weinberg, V.; Carroll, P. R.; Tlsty, T. D., Minichromosome maintenance protein 2 expression in prostate: Characterization and association with outcome after therapy for cancer. Clin. Cancer Res. 2001, 7 (9), 2712-2718.
(15) Tan, D. F.; Huberman, J. A.; Hyland, A.; Loewen, G. M.; Brooks, J. S.; Beck, A. F.; Todorov, I. T.; Bepler, G., MCM2--a promising marker for premalignant lesions of the lung: a cohort study. BMC Cancer 2001, 1, 6.
(16) Yang, J.; Ramnath, N.; Moysich, K. B.; Asch, H. L.; Swede, H.; Alrawi, S. J.; Huberman, J.; Geradts, J.; Brooks, J. S.; Tan, D., Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer. BMC Cancer 2006, 6, 203.
(17) Simon, N. E.; Schwacha, A., The Mcm2-7 Replicative Helicase: A Promising Chemotherapeutic Target. BioMed Res. Int. 2014, 2014, 549719.
(18) Kunnev, D.; Rusiniak, M. E.; Kudla, A.; Freeland, A.; Cady, G. K.; Pruitt, S. C., DNA damage response and tumorigenesis in Mcm2-deficient mice. Oncogene 2010, 29 (25), 3630-3638.
(19) Pruitt, S. C.; Bailey, K. J.; Freeland, A., Reduced Mcm2 expression results in severe stem/progenitor cell deficiency and cancer. Stem Cells 2007, 25 (12), 3121-3132.
(20) Liu, Y.; He, G.; Wang, Y.; Guan, X.; Pang, X.; Zhang, B., MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells. Toxicol. Lett. 2013, 221 (1), 23-30.
(21) Zhang, X.; Teng, Y.; Yang, F.; Wang, M.; Hong, X.; Ye, L. G.; Gao, Y. N.; Chen, G. Y., MCM2 is a therapeutic target of lovastatin in human non-small cell lung carcinomas. Oncol. Rep. 2015, 33 (5), 2599-2605.
(22) Hubbard, M. J.; Cohen, P., On target with a new mechanism for the regulation of protein phosphorylation. Trends Biochem. Sci. 1993, 18 (5), 172-177.
(23) Sano, A.; Nakamura, H., Chemo-affinity of titania for the column-switching HPLC analysis of phosphopeptides. Anal. Sci. 2004, 20 (3), 565-566.
(24) Haydon, C. E.; Eyers, P. A.; Aveline-Wolf, L. D.; Resing, K. A.; Maller, J. L.; Ahn, N. G., Identification of novel phosphorylation sites on Xenopus laevis Aurora A and analysis of phosphopeptide enrichment by immobilized metal-affinity chromatography. Mol. Cell Proteomics 2003, 2 (10), 1055-1067.
(25) Ficarro, S. B.; McCleland, M. L.; Stukenberg, P. T.; Burke, D. J.; Ross, M. M.; Shabanowitz, J.; Hunt, D. F.; White, F. M., Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat. Biotechnol. 2002, 20 (3), 301-305.
(26) Ndassa, Y. M.; Orsi, C.; Marto, J. A.; Chen, S.; Ross, M. M., Improved immobilized metal affinity chromatography for large-scale phosphoproteomics applications. J. Proteome Res. 2006, 5 (10), 2789-2799.
(27) Ballif, B. A.; Villen, J.; Beausoleil, S. A.; Schwartz, D.; Gygi, S. P., Phosphoproteomic analysis of the developing mouse brain. Mol. Cell. Proteomics 2004, 3 (11), 1093-1101.
(28) Beausoleil, S. A.; Jedrychowski, M.; Schwartz, D.; Elias, J. E.; Villen, J.; Li, J.; Cohn, M. A.; Cantley, L. C.; Gygi, S. P., Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc. Natl. Acad. Sci. U S A 2004, 101 (33), 12130-12135.
(29) Kokubu, M.; Ishihama, Y.; Sato, T.; Nagasu, T.; Oda, Y., Specificity of immobilized metal affinity-based IMAC/C18 tip enrichment of phosphopeptides for protein phosphorylation analysis. Anal. Chem. 2005, 77 (16), 5144-5154.
(30) Larsen, M. R.; Thingholm, T. E.; Jensen, O. N.; Roepstorff, P.; Jorgensen, T. J. D., Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol. Cell. Proteomics 2005, 4 (7), 873-886.
(31) Kweon, H. K.; Hakansson, K., Selective zirconium dioxide-based enrichment of phosphorylated peptides for mass spectrometric analysis. Anal. Chem. 2006, 78 (6), 1743-1749.
(32) Wolschin, F.; Wienkoop, S.; Weckwerth, W., Enrichment of phosphorylated proteins and peptides from complex mixtures using metal oxide/hydroxide affinity chromatography (MOAC). Proteomics 2005, 5 (17), 4389-4397.
(33) Sugiyama, N.; Masuda, T.; Shinoda, K.; Nakamura, A.; Tomita, M.; Ishihama, Y., Phosphopeptide enrichment by aliphatic hydroxy acid-modified metal oxide chromatography for nano-LC-MS/MS in proteomics applications. Mol. Cell. Proteomics 2007, 6 (6), 1103-1109.
(34) 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.
(35) Ku, W.-C.; Sugiyama, N.; Ishihama, Y., Large-Scale Protein Phosphorylation Analysis by Mass Spectrometry-Based Phosphoproteomics. In T Protein Kinase Technologies, 2012; Vol. 68, pp 35-46.
(36) Olsen, J. V.; de Godoy, L. M.; Li, G.; Macek, B.; Mortensen, P.; Pesch, R.; Makarov, A.; Lange, O.; Horning, S.; Mann, M., Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol. Cell. Proteomics 2005, 4 (12), 2010-2021.
(37) Vogelstein, B.; Lane, D.; Levine, A. J., Surfing the p53 network. Nature 2000, 408 (6810), 307-310.
(38) Bougeard, G.; Hadj-Rabia, S.; Faivre, L.; Sarafan-Vasseur, N.; Frebourg, T., The Rapp-Hodgkin syndrome results from mutations of the TP63 gene. Eur. J. Hum. Genet. 2003, 11 (9), 700-704.
(39) Cox, J.; Mann, M., MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 2008, 26 (12), 1367-1372.
(40) Cox, J.; Neuhauser, N.; Michalski, A.; Scheltema, R. A.; Olsen, J. V.; Mann, M., Andromeda: a peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 2011, 10 (4), 1794-1805.
(41) Seet, B. T.; Dikic, I.; Zhou, M. M.; Pawson, T., Reading protein modifications with interaction domains. Nat. Rev. Mol. Cell Biol. 2006, 7 (7), 473-483.
(42) Macheret, M.; Halazonetis, T. D., DNA replication stress as a hallmark of cancer. Annu. Rev. Pathol. 2015, 10, 425-448.
(43) Pogorelcnik, B.; Perdih, A.; Solmajer, T., Recent developments of DNA poisons--human DNA topoisomerase IIalpha inhibitors--as anticancer agents. Curr. Pharm. Des. 2013, 19 (13), 2474-2488.
(44) Keating, M. J.; Kantarjian, H.; Talpaz, M.; Redman, J.; Koller, C.; Barlogie, B.; Velasquez, W.; Plunkett, W.; Freireich, E. J.; McCredie, K. B., Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood 1989, 74 (1), 19-25.
(45) Singh, D. K.; Krishna, S.; Chandra, S.; Shameem, M.; Deshmukh, A. L.; Banerjee, D., Human DNA ligases: a comprehensive new look for cancer therapy. Med. Res. Rev. 2014, 34 (3), 567-595.
(46) Tan, Z.; Wortman, M.; Dillehay, K. L.; Seibel, W. L.; Evelyn, C. R.; Smith, S. J.; Malkas, L. H.; Zheng, Y.; Lu, S.; Dong, Z., Small-molecule targeting of proliferating cell nuclear antigen chromatin association inhibits tumor cell growth. Mol. Pharmacol. 2012, 81 (6), 811-819.
(47) Aye, Y.; Li, M.; Long, M. J.; Weiss, R. S., Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies. Oncogene 2015, 34 (16), 2011-2021.
(48) Li, Y. Q.; Wang, Y. Q.; Zhang, C. B.; Yuan, W. Z.; Wang, J.; Zhu, C. B.; Chen, L.; Huang, W.; Zeng, W. Q.; Wu, X. S.; Liu, M. Y., ZNF322, a novel human C2H2 Kriippel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways. Biochem. Biophys. Res. Commun. 2004, 325 (4), 1383-1392.
(49) Jen, J. L., L. L.; Chen, H. T.; Liao, S. Y.; Lo, F. Y.; Tang, Y. A.; Hsu, H. S.; Salgia, R.; Hsu, C. L.; Huang, H. C.; Juan, H. F.;Wang, Y. C., Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer. Oncogene (in press)
(50) Harsha, H. C.; Pandey, A., Phosphoproteomics in cancer. Mol. Oncol. 2010, 4 (6), 482-495.
(51) Brognard, J.; Hunter, T., Protein kinase signaling networks in cancer. Curr. Opin. Genet. Dev. 2011, 21 (1), 4-11.
(52) Cooper, T. A.; Wan, L. L.; Dreyfuss, G., RNA and Disease. Cell 2009, 136 (4), 777-793.
(53) Venables, J. P.; Klinck, R.; Koh, C.; Gervais-Bird, J.; Bramard, A.; Inkel, L.; Durand, M.; Couture, S.; Froehlich, U.; Lapointe, E.; Lucier, J. F.; Thibault, P.; Rancourt, C.; Tremblay, K.; Prinos, P.; Chabot, B.; Elela, S. A., Cancer-associated regulation of alternative splicing. Nat. Struct. Mol. Biol. 2009, 16 (6), 670-676.
(54) Lau, K. M.; Chan, Q. K. Y.; Pang, J. C. S.; Li, K. K. W.; Yeung, W. W.; Chung, N. Y. F.; Lui, P. C.; Tam, Y. S.; Li, H. M.; Zhou, L.; Wang, Y.; Mao, Y.; Ng, H. K., Minichromosome maintenance proteins 2, 3 and 7 in medulloblastoma: overexpression and involvement in regulation of cell migration and invasion. Oncogene 2010, 29 (40), 5475-5489.
(55) Montagnoli, A.; Valsasina, B.; Brotherton, D.; Troiani, S.; Rainoldi, S.; Tenca, P.; Molinari, A.; Santocanale, C., Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases. J. Biol. Chem. 2006, 281 (15), 10281-10290.
(56) Cortez, D.; Glick, G.; Elledge, S. J., Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc. Natl. Acad. Sci. U S A 2004, 101 (27), 10078-10083.
(57) Tsuji, T.; Ficarro, S. B.; Jiang, W., Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells. Mol. Biol. Cell 2006, 17 (10), 4459-4472.
(58) Bustin, M., Revised nomenclature for high mobility group (HMG) chromosomal proteins. Trends Biochem. Sci. 2001, 26 (3), 152-153.
(59) Catez, F.; Hock, R., Binding and interplay of HMG proteins on chromatin: Lessons from live cell imaging. Biochim. Biophys. Acta, Gene Regul. Mech. 2010, 1799 (1-2), 15-27.
(60) Fusco, A.; Fedele, M., Roles of HMGA proteins in cancer. Nat. Rev. Cancer 2007, 7 (12), 899-910.
(61) Fedele, M.; Fusco, A., HMGA and cancer. Biochim. Biophys. Acta 2010, 1799 (1-2), 48-54.
(62) Zhang, Z.; Wang, Q.; Chen, F.; Liu, J., Elevated expression of HMGA1 correlates with the malignant status and prognosis of non-small cell lung cancer. Tumour Biol. 2015, 36 (2), 1213-1219.
(63) Piekielko, A.; Drung, A.; Rogalla, P.; Schwanbeck, R.; Heyduk, T.; Gerharz, M.; Bullerdiek, J.; Wisniewski, J. R., Distinct organization of DNA complexes of various HMGI/Y family proteins and their modulation upon mitotic phosphorylation. J. Biol. Chem. 2001, 276 (3), 1984-1992.
(64) Wang, D. Z.; Ray, P.; Boothby, M., Interleukin 4-Inducible Phosphorylation of Hmg-I(Y) Is Inhibited by Rapamycin. J. Biol. Chem. 1995, 270 (39), 22924-22932.
(65) Edberg, D. D.; Bruce, J. E.; Siems, W. F.; Reeves, R., In vivo posttranslational modifications of the high mobility group A1a proteins in breast cancer cells of differing metastatic potential. Biochemistry 2004, 43 (36), 11500-11515.
(66) Sgarra, R.; Rustighi, A.; Tessari, M. A.; Di Bernardo, J.; Altamura, S.; Fusco, A.; Manfioletti, G.; Giancotti, V., Nuclear phosphoproteins HMGA and their relationship with chromatin structure and cancer. FEBS Lett. 2004, 574 (1-3), 1-8.
(67) Chiefari, E.; Nevolo, M. T.; Arcidiacono, B.; Maurizio, E.; Nocera, A.; Iiritano, S.; Sgarra, R.; Possidente, K.; Palmieri, C.; Paonessa, F.; Brunetti, G.; Manfioletti, G.; Foti, D.; Brunetti, A., HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway. Sci. Rep. 2012, 2.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top