Hsp90 inhibitor SNX-7081 dysregulates proteins involved with DNA repair and replication and the cell cycle in human chronic lymphocytic leukemia (CLL) cells

Journal of Proteome Research

Volumn 12, Issue 4, 2013, Pages 1710-1722

  Che, Yiping ^a   Best, O Giles ^b   Zhong, Ling ^c   Kaufman, Kimberley L ^a   MacTier, Swetlana ^a   Raftery, Mark ^c   Graves, Lee M ^d   Mulligan, Stephen P ^b   Christopherson, Richard I ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b ROYAL NORTH SHORE HOSPITAL   (Australia)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

chronic lymphocytic leukemia; drug mechanism; Hsp90 inhibitor; iTRAQ; RT PCR; Western blot

Indexed keywords

CYCLIN D1; GLUCOSE REGULATED PROTEIN 78; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; HLA DR ANTIGEN; PROTEIN P53; SNX 7081; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; B CELL LEUKEMIA; CELL CYCLE REGULATION; CELL VIABILITY; CHRONIC LYMPHATIC LEUKEMIA; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA REPAIR; DNA REPLICATION; HUMAN; HUMAN CELL; LEUKEMIA CELL; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULARLY TARGETED THERAPY; ONCOGENE C MYC; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEOMICS; RAJI CELL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

APOPTOSIS; BENZAMIDES; CELL CYCLE; CELL LINE, TUMOR; DNA REPAIR; DNA REPLICATION; GENES, P53; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; PROTEOME; REPRODUCIBILITY OF RESULTS; TANDEM MASS SPECTROMETRY;

EID: 84875952820     PISSN: 15353893     EISSN: 15353907     Source Type: Journal    
DOI: 10.1021/pr301055y     Document Type: Article

References (91)

1. SNX-7081 arrests the cell cycle
2. Fludarabine, cyclophosphamide, and mitoxantrone epair
3. Bosch, F.; Ferrer, A.; Villamor, N.; Gonzalez, M.; Briones, J.; Gonzalez-Barca, E.; Abella, E.; Gardella, S.; Escoda, L.; Perez-Ceballos, E.; Asensi, A.; Sayas, M. J.; Font, L.; Altes, A.; Muntanola, A.; Bertazzoni, P.; Rozman, M.; Aymerich, M.; Gine, E.; Montserrat, E. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication Clin. Cancer Res. 2008, 14 (1) 155-61
4. Chen, J.; McMillan, N. A. Molecular basis of pathogenesis, prognosis and therapy in chronic lymphocytic leukaemia Cancer Biol Ther. 2008, 7 (2) 174-9
5. Diehl, L. F.; Karnell, L. H.; Menck, H. R. The American College of Surgeons Commission on Cancer and the American Cancer Society. The National Cancer Data Base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia Cancer 1999, 86 (12) 2684-92
6. Andreeff, M.; Darzynkiewicz, Z.; Sharpless, T. K.; Clarkson, B. D.; Melamed, M. R. Discrimination of human leukemia subtypes by flow cytometric analysis of cellular DNA and RNA Blood 1980, 55 (2) 282-93
7. Tam, C. S.; O'Brien, S.; Wierda, W.; Kantarjian, H.; Wen, S.; Do, K. A.; Thomas, D. A.; Cortes, J.; Lerner, S.; Keating, M. J. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia Blood 2008, 112 (4) 975-80
8. Zenz, T.; Krober, A.; Scherer, K.; Habe, S.; Buhler, A.; Benner, A.; Denzel, T.; Winkler, D.; Edelmann, J.; Schwanen, C.; Dohner, H.; Stilgenbauer, S. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up Blood 2008, 112 (8) 3322-9
9. Henrich, S.; Christopherson, R. I. Multiple forms of nuclear p53 formed in human Raji and MEC1 cells treated with fludarabine Leukemia 2008, 22 (3) 657-60
10. Isobe, M.; Emanuel, B. S.; Givol, D.; Oren, M.; Croce, C. M. Localization of gene for human p53 tumour antigen to band 17p13 Nature 1986, 320 (6057) 84-5
11. Kern, S. E.; Kinzler, K. W.; Bruskin, A.; Jarosz, D.; Friedman, P.; Prives, C.; Vogelstein, B. Identification of p53 as a sequence-specific DNA-binding protein Science 1991, 252 (5013) 1708-11
12. Daniel, P. T.; Wieder, T.; Sturm, I.; Schulze-Osthoff, K. The kiss of death: promises and failures of death receptors and ligands in cancer therapy Leukemia 2001, 15 (7) 1022-32
13. Schelwies, K.; Sturm, I.; Grabowski, P.; Scherubl, H.; Schindler, I.; Hermann, S.; Stein, H.; Buhr, H. J.; Riecken, E. O.; Zeitz, M.; Dorken, B.; Daniel, P. T. Analysis of p53/BAX in primary colorectal carcinoma: low BAX protein expression is a negative prognostic factor in UICC stage III tumors Int. J. Cancer 2002, 99 (4) 589-96
14. Nakano, K.; Vousden, K. H. PUMA, a novel proapoptotic gene, is induced by p53 Mol. Cell 2001, 7 (3) 683-94
15. Moroni, M. C.; Hickman, E. S.; Lazzerini Denchi, E.; Caprara, G.; Colli, E.; Cecconi, F.; Muller, H.; Helin, K. Apaf-1 is a transcriptional target for E2F and p53 Nat. Cell Biol. 2001, 3 (6) 552-8
16. Silber, R.; Degar, B.; Costin, D.; Newcomb, E. W.; Mani, M.; Rosenberg, C. R.; Morse, L.; Drygas, J. C.; Canellakis, Z. N.; Potmesil, M. Chemosensitivity of lymphocytes from patients with B-cell chronic lymphocytic leukemia to chlorambucil, fludarabine, and camptothecin analogs Blood 1994, 84 (10) 3440-6
17. Sturm, I.; Bosanquet, A. G.; Hermann, S.; Guner, D.; Dorken, B.; Daniel, P. T. Mutation of p53 and consecutive selective drug resistance in B-CLL occurs as a consequence of prior DNA-damaging chemotherapy Cell Death Differ. 2003, 10 (4) 477-84
18. Stilgenbauer, S.; Sander, S.; Bullinger, L.; Benner, A.; Leupolt, E.; Winkler, D.; Krober, A.; Kienle, D.; Lichter, P.; Dohner, H. Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival Haematologica 2007, 92 (9) 1242-5
19. Tsimberidou, A. M.; Keating, M. J. Treatment of patients with fludarabine-refractory chronic lymphocytic leukemia: need for new treatment options Leuk. Lymphoma 2010, 51 (7) 1188-99
20. Goetz, M. P.; Toft, D. O.; Ames, M. M.; Erlichman, C. The Hsp90 chaperone complex as a novel target for cancer therapy Ann. Oncol. 2003, 14 (8) 1169-76
21. Brown, M. A.; Zhu, L.; Schmidt, C.; Tucker, P. W. Hsp90 - from signal transduction to cell transformation Biochem. Biophys. Res. Commun. 2007, 363 (2) 241-6
22. Maloney, A.; Workman, P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds Expert Opin. Biol. Ther. 2002, 2 (1) 3-24
23. Zhao, R.; Houry, W. A. Hsp90: a chaperone for protein folding and gene regulation Biochem. Cell Biol. 2005, 83 (6) 703-10
24. Trepel, J.; Mollapour, M.; Giaccone, G.; Neckers, L. Targeting the dynamic HSP90 complex in cancer Nat. Rev. Cancer 2010, 10 (8) 537-49
25. Calderwood, S. K.; Khaleque, M. A.; Sawyer, D. B.; Ciocca, D. R. Heat shock proteins in cancer: chaperones of tumorigenesis Trends Biochem. Sci. 2006, 31 (3) 164-72
26. Koga, F.; Xu, W.; Karpova, T. S.; McNally, J. G.; Baron, R.; Neckers, L. Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent Akt and Erk activation Proc. Natl. Acad. Sci. U.S.A. 2006, 103 (30) 11318-22
27. Lu, Z.; Jin, Y.; Qiu, L.; Lai, Y.; Pan, J. Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation Cancer Lett. 2010, 290 (2) 182-91
28. Blagosklonny, M. V.; Toretsky, J.; Bohen, S.; Neckers, L. Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90 Proc. Natl. Acad. Sci. U.S.A. 1996, 93 (16) 8379-83
29. Ciocca, D. R.; Calderwood, S. K. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications Cell Stress Chaperones 2005, 10 (2) 86-103
30. Richardson, P. G.; Mitsiades, C. S.; Laubach, J. P.; Lonial, S.; Chanan-Khan, A. A.; Anderson, K. C. Inhibition of heat shock protein 90 (HSP90) as a therapeutic strategy for the treatment of myeloma and other cancers Br. J. Hamaetol. 2011, 152 (4) 367-79
31. Hertlein, E.; Wagner, A. J.; Jones, J.; Lin, T. S.; Maddocks, K. J.; Towns, W. H., 3rd; Goettl, V. M.; Zhang, X.; Jarjoura, D.; Raymond, C. A.; West, D. A.; Croce, C. M.; Byrd, J. C.; Johnson, A. J. 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition Blood 2010, 116 (1) 45-53
32. Janz, M.; Stuhmer, T.; Vassilev, L. T.; Bargou, R. C. Pharmacologic activation of p53-dependent and p53-independent apoptotic pathways in Hodgkin/Reed-Sternberg cells Leukemia 2007, 21 (4) 772-9
33. Best, O. G.; Singh, N.; Forsyth, C.; Mulligan, S. P. The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway Br. J. Hamaetol. 2010, 151 (2) 185-8
34. Kim, Y. S.; Alarcon, S. V.; Lee, S.; Lee, M. J.; Giaccone, G.; Neckers, L.; Trepel, J. B. Update on Hsp90 inhibitors in clinical trial Curr. Top. Med. Chem. 2009, 9 (15) 1479-92
35. Rice, J. W.; Veal, J. M.; Fadden, R. P.; Barabasz, A. F.; Partridge, J. M.; Barta, T. E.; Dubois, L. G.; Huang, K. H.; Mabbett, S. R.; Silinski, M. A.; Steed, P. M.; Hall, S. E. Small molecule inhibitors of Hsp90 potently affect inflammatory disease pathways and exhibit activity in models of rheumatoid arthritis Arthritis Rheum. 2008, 58 (12) 3765-75
36. Stacchini, A.; Aragno, M.; Vallario, A.; Alfarano, A.; Circosta, P.; Gottardi, D.; Faldella, A.; Rege-Cambrin, G.; Thunberg, U.; Nilsson, K.; Caligaris-Cappio, F. MEC1 and MEC2: two new cell lines derived from B-chronic lymphocytic leukaemia in prolymphocytoid transformation Leuk Res. 1999, 23 (2) 127-36
37. Gong, B.; Almasan, A. Differential upregulation of p53-responsive genes by genotoxic stress in hematopoietic cells containing wild-type and mutant p53 Gene Expr. 1999, 8 (4) 197-206
38. Wolf, D.; Rotter, V. Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells Proc. Natl. Acad. Sci. U.S.A. 1985, 82 (3) 790-4
39. Duthu, A.; Debuire, B.; Romano, J.; Ehrhart, J. C.; Fiscella, M.; May, E.; Appella, E.; May, P. p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas Oncogene 1992, 7 (11) 2161-7
40. Almazi, J. G.; Mactier, S.; Best, O. G.; Crossett, B.; Mulligan, S. P.; Christopherson, R. I. Fludarabine nucleoside induces accumulations of p53, p63 and p73 in the nuclei of human B-lymphoid cell lines, with cytosolic and mitochondrial increases in p53 Proteomics Clin. Appl. 2012, 6 (5-6) 279-90
41. Mactier, S.; Henrich, S.; Che, Y.; Kohnke, P. L.; Christopherson, R. I. Comprehensive proteomic analysis of the effects of purine analogs on human Raji B-cell lymphoma J. Proteome Res. 2011, 10 (3) 1030-42
42. Burg, D. W.; Lauro, F. M.; Williams, T. J.; Raftery, M. J.; Guilhaus, M.; Cavicchioli, R. Analyzing the hydrophobic proteome of the antarctic archaeon Methanococcoides burtonii using differential solubility fractionation J. Proteome Res. 2010, 9 (2) 664-76
43. Bustin, S. A. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems J. Mol. Endocrinol. 2002, 29 (1) 23-39
44. Zenz, T.; Habe, S.; Denzel, T.; Mohr, J.; Winkler, D.; Buhler, A.; Sarno, A.; Groner, S.; Mertens, D.; Busch, R.; Hallek, M.; Dohner, H.; Stilgenbauer, S. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial Blood 2009, 114 (13) 2589-97
45. Paraiso, K. H.; Haarberg, H. E.; Wood, E.; Rebecca, V. W.; Chen, Y. A.; Xiang, Y.; Ribas, A.; Lo, R. S.; Weber, J. S.; Sondak, V. K.; John, J. K.; Sarnaik, A. A.; Koomen, J. M.; Smalley, K. S. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms Clin. Cancer Res. 2012, 18 (9) 2502-14
46. Madrigal-Matute, J.; Fernandez-Garcia, C. E.; Gomez-Guerrero, C.; Lopez-Franco, O.; Munoz-Garcia, B.; Egido, J.; Blanco-Colio, L. M.; Martin-Ventura, J. L. HSP90 inhibition by 17-DMAG attenuates oxidative stress in experimental atherosclerosis Cardiovasc. Res. 2012, 95 (1) 116-23
47. Elo, M. A.; Kaarniranta, K.; Helminen, H. J.; Lammi, M. J. Hsp90 inhibitor geldanamycin increases hsp70 mRNA stabilisation but fails to activate HSF1 in cells exposed to hydrostatic pressure Biochim. Biophys. Acta 2005, 1743 (1-2) 115-9
48. Stingl, L.; Stuhmer, T.; Chatterjee, M.; Jensen, M. R.; Flentje, M.; Djuzenova, C. S. Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell-cycle impairment, increased DNA damage and repair protraction Br. J. Cancer 2010, 102 (11) 1578-91
49. Yao, J. Q.; Liu, Q. H.; Chen, X.; Yang, Q.; Xu, Z. Y.; Hu, F.; Wang, L.; Li, J. M. Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin inhibits the proliferation of ARPE-19 cells J. Biomed. Sci. 2010, 17, 30
50. Bai, C.; Sen, P.; Hofmann, K.; Ma, L.; Goebl, M.; Harper, J. W.; Elledge, S. J. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box Cell 1996, 86 (2) 263-74
51. Barlat, I.; Maurier, F.; Duchesne, M.; Guitard, E.; Tocque, B.; Schweighoffer, F. A role for Sam68 in cell cycle progression antagonized by a spliced variant within the KH domain J. Biol. Chem. 1997, 272 (6) 3129-32
52. Pagano, M.; Theodoras, A. M.; Tam, S. W.; Draetta, G. F. Cyclin D1-mediated inhibition of repair and replicative DNA synthesis in human fibroblasts Genes Dev. 1994, 8 (14) 1627-39
53. Li, Z.; Jiao, X.; Wang, C.; Shirley, L. A.; Elsaleh, H.; Dahl, O.; Wang, M.; Soutoglou, E.; Knudsen, E. S.; Pestell, R. G. Alternative cyclin D1 splice forms differentially regulate the DNA damage response Cancer Res. 2010, 70 (21) 8802-11
54. Jirawatnotai, S.; Hu, Y.; Michowski, W.; Elias, J. E.; Becks, L.; Bienvenu, F.; Zagozdzon, A.; Goswami, T.; Wang, Y. E.; Clark, A. B.; Kunkel, T. A.; van Harn, T.; Xia, B.; Correll, M.; Quackenbush, J.; Livingston, D. M.; Gygi, S. P.; Sicinski, P. A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers Nature 2011, 474 (7350) 230-4
55. Bartek, J.; Lukas, J. DNA repair: Cyclin D1 multitasks Nature 2011, 474 (7350) 171-2
56. Funk, J. O.; Waga, S.; Harry, J. B.; Espling, E.; Stillman, B.; Galloway, D. A. Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein Genes Dev. 1997, 11 (16) 2090-100
57. Wang, X.; Heuvelman, D. M.; Carroll, J. A.; Dufield, D. R.; Masferrer, J. L. Geldanamycin-induced PCNA degradation in isolated Hsp90 complex from cancer cells Cancer Invest. 2010, 28 (6) 635-41
58. Dengler, M. A.; Gutekunst, M.; Kopacz, S.; Horn, H.; Hofmann, U.; Schwab, M.; MD, G. O.; Kuip, H.; Aulitzky, W. E. Cyclin D1 over-expressing mantle cell lymphoma cells are hypersensitive to inhibition of fatty acid synthase (FASN) 53rd ASH Annu. Meeting Exposition 2011, 625, 1656
59. Zeng, L.; Wu, G. Z.; Goh, K. J.; Lee, Y. M.; Ng, C. C.; You, A. B.; Wang, J.; Jia, D.; Hao, A.; Yu, Q.; Li, B. Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis PLoS One 2008, 3 (6) e2329
60. Wu, X.; Serrano, M.; Zou, Y.; Zhang, J. Non-homologues end joining mediates fatty acid synthase(FASN)-associated resistance to DNA-damaging chemotherapeutics; the 103rd Annual Meeting of the American Association for Cancer Research Cancer Res. 2012, 72 (8) 2124
61. Philipp, A.; Schneider, A.; Vasrik, I.; Finke, K.; Xiong, Y.; Beach, D.; Alitalo, K.; Eilers, M. Repression of cyclin D1: a novel function of MYC Mol. Cell. Biol. 1994, 14 (6) 4032-43
62. Das, S. K.; Hashimoto, T.; Shimizu, K.; Yoshida, T.; Sakai, T.; Sowa, Y.; Komoto, A.; Kanazawa, K. Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1 Biochim. Biophys. Acta 2005, 1726 (3) 328-35
63. Murphree, A. L.; Benedict, W. F. Retinoblastoma: clues to human oncogenesis Science 1984, 223 (4640) 1028-33
64. Bartkova, J.; Gron, B.; Dabelsteen, E.; Bartek, J. Cell-cycle regulatory proteins in human wound healing Arch. Oral Biol. 2003, 48 (2) 125-32
65. Sterner, J. M.; Dew-Knight, S.; Musahl, C.; Kornbluth, S.; Horowitz, J. M. Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7 Mol. Cell. Biol. 1998, 18 (5) 2748-57
66. Scrima, A.; Konickova, R.; Czyzewski, B. K.; Kawasaki, Y.; Jeffrey, P. D.; Groisman, R.; Nakatani, Y.; Iwai, S.; Pavletich, N. P.; Thoma, N. H. Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex Cell 2008, 135 (7) 1213-23
67. Shen, X.; Mizuguchi, G.; Hamiche, A.; Wu, C. A chromatin remodelling complex involved in transcription and DNA processing Nature 2000, 406 (6795) 541-4
68. Ikura, T.; Ogryzko, V. V.; Grigoriev, M.; Groisman, R.; Wang, J.; Horikoshi, M.; Scully, R.; Qin, J.; Nakatani, Y. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis Cell 2000, 102 (4) 463-73
69. Fujii, Y.; Kato, T.; Kubota, N.; Fujimori, A.; Niwa, O.; Okayasu, R. p53 independent radio-sensitization of human lymphoblastoid cell lines by Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin Oncol. Rep. 2010, 23 (1) 199-203
70. McNamara, A. V.; Barclay, M.; Watson, A. J.; Jenkins, J. R. Hsp90 inhibitors sensitise human colon cancer cells to topoisomerase I poisons by depletion of key anti-apoptotic and cell cycle checkpoint proteins Biochem. Pharmacol. 2012, 83 (3) 355-67
71. Best, O. G.; Che, Y.; Singh, N.; Forsyth, C.; Christopherson, R. I.; Mulligan, S. P. The Hsp90 inhibitor SNX-7081 synergizes with and restores sensitivity to fludarabine in chronic lymphocytic leukemia cells with lesions in the TP53 pathway: a potential treatment strategy for fludarabine refractory disease Leuk. Lymphoma 2012, 53 (7) 1367-75
72. Koll, T. T.; Feis, S. S.; Wright, M. H.; Teniola, M. M.; Richardson, M. M.; Robles, A. I.; Bradsher, J.; Capala, J.; Varticovski, L. HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair Mol. Cancer Ther. 2008, 7 (7) 1985-92
73. Dote, H.; Burgan, W. E.; Camphausen, K.; Tofilon, P. J. Inhibition of hsp90 compromises the DNA damage response to radiation Cancer Res. 2006, 66 (18) 9211-20
74. Barker, C. R.; McNamara, A. V.; Rackstraw, S. A.; Nelson, D. E.; White, M. R.; Watson, A. J.; Jenkins, J. R. Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage Nucleic Acids Res. 2006, 34 (4) 1148-57
75. Connor, J. H.; McKenzie, M. O.; Parks, G. D.; Lyles, D. S. Antiviral activity and RNA polymerase degradation following Hsp90 inhibition in a range of negative strand viruses Virology 2007, 362 (1) 109-19
76. He, X.; Arslan, A. D.; Pool, M. D.; Ho, T. T.; Darcy, K. M.; Coon, J. S.; Beck, W. T. Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer Oncogene 2011, 30 (3) 356-65
77. Roberts, C. W.; Orkin, S. H. The SWI/SNF complex - chromatin and cancer Nat. Rev. Cancer 2004, 4 (2) 133-42
78. Wilson, B. G.; Roberts, C. W. SWI/SNF nucleosome remodellers and cancer Nat. Rev. Cancer 2011, 11 (7) 481-92
79. Miller, J.; Horner, A.; Stacy, T.; Lowrey, C.; Lian, J. B.; Stein, G.; Nuckolls, G. H.; Speck, N. A. The core-binding factor beta subunit is required for bone formation and hematopoietic maturation Nat. Genet. 2002, 32 (4) 645-9
80. Zhang, X.; Clark, A. F.; Yorio, T. Heat shock protein 90 is an essential molecular chaperone for nuclear transport of glucocorticoid receptor beta Invest. Ophthalmol. Vis. Sci. 2006, 47 (2) 700-8
81. Dakappagari, N.; Neely, L.; Tangri, S.; Lundgren, K.; Hipolito, L.; Estrellado, A.; Burrows, F.; Zhang, H. An investigation into the potential use of serum Hsp70 as a novel tumour biomarker for Hsp90 inhibitors Biomarkers 2010, 15 (1) 31-8
82. Reddy, R. K.; Mao, C.; Baumeister, P.; Austin, R. C.; Kaufman, R. J.; Lee, A. S. Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation J. Biol. Chem. 2003, 278 (23) 20915-24
83. Racek, T.; Buhlmann, S.; Rust, F.; Knoll, S.; Alla, V.; Putzer, B. M. Transcriptional repression of the prosurvival endoplasmic reticulum chaperone GRP78/BIP by E2F1 J. Biol. Chem. 2008, 283 (49) 34305-14
84. Arora, S.; Yang, J. M.; Kinzy, T. G.; Utsumi, R.; Okamoto, T.; Kitayama, T.; Ortiz, P. A.; Hait, W. N. Identification and characterization of an inhibitor of eukaryotic elongation factor 2 kinase against human cancer cell lines Cancer Res. 2003, 63 (20) 6894-9
85. Yang, J.; Yang, J. M.; Iannone, M.; Shih, W. J.; Lin, Y.; Hait, W. N. Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin Cancer Res. 2001, 61 (10) 4010-6
86. Gan, W.; LaCelle, M.; Rhoads, R. E. Functional characterization of the internal ribosome entry site of eIF4G mRNA J. Biol. Chem. 1998, 273 (9) 5006-12
87. Hu, J. Mechanisms of eukaryotic translation initiation factor 4F (eIF4F) inhibitors in combating cancer J. Undergrad. Life Sci. 2008, 2 (1) 68-72
88. Raymond, C. K.; Kas, A.; Paddock, M.; Qiu, R.; Zhou, Y.; Subramanian, S.; Chang, J.; Palmieri, A.; Haugen, E.; Kaul, R.; Olson, M. V. Ancient haplotypes of the HLA Class II region Genome Res. 2005, 15 (9) 1250-7
89. Groth, A.; Kloss, S.; von Strandmann, E. P.; Koehl, U.; Koch, J. Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance J. Innate Immun. 2011, 3 (4) 344-54
90. Sampalo, A.; Brieva, J. A. Humoral immunodeficiency in chronic lymphocytic leukemia: role of CD95/CD95L in tumoral damage and escape Leuk. Lymphoma 2002, 43 (4) 881-4
91. Yun, T. J.; Harning, E. K.; Giza, K.; Rabah, D.; Li, P.; Arndt, J. W.; Luchetti, D.; Biamonte, M. A.; Shi, J.; Lundgren, K.; Manning, A.; Kehry, M. R. EC144, a synthetic inhibitor of heat shock protein 90, blocks innate and adaptive immune responses in models of inflammation and autoimmunity J. Immunol. 2011, 186 (1) 563-75