Nuclear export of proteins and drug resistance in cancer

Biochemical Pharmacology

Volumn 83, Issue 8, 2012, Pages 1021-1032

  Turner, Joel G ^a   Dawson, Jana ^a   Sullivan, Daniel M ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

CRM1; Drug resistance; Nuclear export signal; Nuclear pore complex; Topoisomerase

Indexed keywords

ANTINEOPLASTIC AGENT; APC; CBS 9106; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN DEPENDENT KINASE INHIBITOR 1B; DNA TOPOISOMERASE; DNA TOPOISOMERASE (ATP HYDROLYSING); DOXORUBICIN; ESTRADIOL RECEPTOR; ETOPOSIDE; EXPORTIN 1; GALECTIN 3; HEAT SHOCK PROTEIN 90; KOSAN 2464; KPT 115; LEPTOMYCIN B; MERLIN; NEURAL WISKOTT ALDRICH SYNDROME PROTEIN; NUCLEOPHOSMIN; PKF 050 637; PKF 050 638; PROTEIN; PROTEIN P53; RAN PROTEIN; RATJADONE A; RATJADONE B; RATJADONE C; TRANSCRIPTION FACTOR FOXO; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALTRATE;

ANOREXIA; CANCER RESISTANCE; CANCER THERAPY; CELL NUCLEUS; CYTOPLASM; GLIOMA; HUMAN; MALAISE; MOLECULAR MECHANICS; NONHUMAN; NUCLEAR PORE COMPLEX; OSTEOSARCOMA; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN STRUCTURE; PROTEIN TARGETING; RETINOBLASTOMA; REVIEW; SIGNAL TRANSDUCTION; UTERINE CERVIX CANCER;

ACTIVE TRANSPORT, CELL NUCLEUS; AMINOPYRIDINES; ANTIGENS, NEOPLASM; ANTINEOPLASTIC AGENTS; DNA TOPOISOMERASES, TYPE II; DNA-BINDING PROTEINS; DRUG RESISTANCE, NEOPLASM; FATTY ACIDS, UNSATURATED; FEMALE; GALECTIN 3; HUMANS; KARYOPHERINS; OVARIAN NEOPLASMS; PANCREATIC NEOPLASMS; PROTEINS; PYRONES; PYRROLIDINONES; RECEPTORS, CYTOPLASMIC AND NUCLEAR;

EID: 84858005605     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2011.12.016     Document Type: Review

References (153)

1. Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol 2005;205:275-92. (Pubitemid 40227997)
2. Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med 2002;53:615-27. (Pubitemid 34177898)
3. Ishikawa T, Ali-Osman F. Glutathione-associated cis- diamminedichloroplatinum(II) metabolism and ATP-dependent efflux from leukemia cells. Molecular characterization of glutathione-platinum complex and its biological significance. J Biol Chem 1993;268:20116-25. (Pubitemid 23278910)
4. Dabholkar M, Vionnet J, Bostick-Bruton F, Yu JJ, Reed E. Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy. J Clin Invest 1994;94:703-8. (Pubitemid 24251002)
5. Fink D, Aebi S, Howell SB. The role of DNA mismatch repair in drug resistance. Clin Cancer Res 1998;4:1-6. (Pubitemid 28062870)
6. Durant ST, Morris MM, Illand M, McKay HJ, McCormick C, Hirst GL, et al. Dependence on RAD52 and RAD1 for anticancer drug resistance mediated by inactivation of mismatch repair genes. Curr Biol 1999;9:51-4. (Pubitemid 29045795)
7. Roe M, Folkes A, Ashworth P, Brumwell J, Chima L, Hunjan S, et al. Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg Med Chem Lett 1999;9:595-600. (Pubitemid 29090660)
8. Goldman B. Multidrug resistance: can new drugs help chemotherapy score against cancer. J Natl Cancer Inst 2003;95:255-7. (Pubitemid 36336473)
9. Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci 2000;11:265-83.
10. Thomas H, Coley HM. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control 2003;10:159-65. (Pubitemid 36437822)
11. Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 1999;39:361-98. (Pubitemid 29222564)
12. Xu Y, Villalona-Calero MA. Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity. Ann Oncol 2002;13:1841-51. (Pubitemid 36040772)
13. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330-8. (Pubitemid 37328853)
14. Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell death. J Clin Oncol 1999;17:1061-70. (Pubitemid 29109340)
15. Kavallaris M, Tait AS, Walsh BJ, He L, Horwitz SB, Norris MD, et al. Multiple microtubule alterations are associated with Vinca alkaloid resistance in human leukemia cells. Cancer Res 2001;61:5803-9. (Pubitemid 32769098)
16. Boyer J, McLean EG, Aroori S, Wilson P, McCulla A, Carey PD, et al. Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan. Clin Cancer Res 2004;10:2158-67. (Pubitemid 38375578)
17. Li XG, Haluska Jr P, Hsiang YH, Bharti A, Kufe DW, Rubin EH. Identification of topoisomerase I mutations affecting both DNA cleavage and interaction with camptothecin. Ann N Y Acad Sci 1996;803:111-27. (Pubitemid 27057979)
18. Meads MB, Gatenby RA, Dalton WS. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 2009;9:665-74.
19. Hazlehurst LA, Landowski TH, Dalton WS. Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death. Oncogene 2003;22:7396-402. (Pubitemid 37487165)
20. Dalton WS. The tumor microenvironment: focus on myeloma. Cancer Treat Rev 2003;29(Suppl 1):11-9. (Pubitemid 36626288)
21. Ungefroren H, Sebens S, Seidl D, Lehnert H, Hass R. Interaction of tumor cells with the microenvironment. Cell Commun Signal 2011;9:18.
22. Kim JW, Ho WJ, Wu BM. The role of the 3D environment in hypoxia-induced drug and apoptosis resistance. Anticancer Res 2011;31:3237-45.
23. Fabbro M, Henderson BR. Regulation of tumor suppressors by nuclear-cytoplasmic shuttling. Exp Cell Res 2003;282:59-69. (Pubitemid 36259901)
24. Kau TR, Silver PA. Nuclear transport as a target for cell growth. Drug Discov Today 2003;8:78-85. (Pubitemid 36139901)
25. Yashiroda Y, Yoshida M. Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs. Curr Med Chem 2003;10:741-8. (Pubitemid 36443230)
26. Turner JG, Marchion DC, Dawson JL, Emmons MF, Hazlehurst LA, Washausen P, et al. Human multiple myeloma cells are sensitized to topoisomerase II inhibitors by CRM1 inhibition. Cancer Res 2009;69:6899-905.
27. Nakamura T, Imai H, Tsunashima N, Nakagawa Y. Molecular cloning and functional expression of nucleolar phospholipid hydroperoxide glutathione peroxidase in mammalian cells. Biochem Biophys Res Commun 2003;311:139-48. (Pubitemid 37303955)
28. Guo YX, Dallmann K, Kwang J. Identification of nucleolus localization signal of betanodavirus GGNNV protein alpha. Virology 2003;306:225-35. (Pubitemid 36299271)
29. Liu J, Du X, Ke Y. Mapping nucleolar localization sequences of 1A6/DRIM. FEBS Lett 2006;580:1405-10. (Pubitemid 43222007)
30. Hodel MR, Corbett AH, Hodel AE. Dissection of a nuclear localization signal. J Biol Chem 2001;276:1317-25. (Pubitemid 32096562)
31. Kanwal C, Li H, Lim CS. Model system to study classical nuclear export signals. AAPS PharmSci 2002;4:E18.
32. Bogerd HP, Fridell RA, Benson RE, Hua J, Cullen BR. Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay. Mol Cell Biol 1996;16:4207-14. (Pubitemid 26251221)
33. Henderson BR, Eleftheriou A. A comparison of the activity, sequence specificity, and CRM1-dependence of different nuclear export signals. Exp Cell Res 2000;256:213-24. (Pubitemid 30211183)
34. Ikuta T, Eguchi H, Tachibana T, Yoneda Y, Kawajiri K. Nuclear localization and export signals of the human aryl hydrocarbon receptor. J Biol Chem 1998;273:2895-904. (Pubitemid 28133939)
35. Munro S, Pelham HR. A C-terminal signal prevents secretion of luminal ER proteins. Cell 1987;48:899-907.
36. Andres DA, Dickerson IM, Dixon JE. Variants of the carboxyl-terminal KDEL sequence direct intracellular retention. J Biol Chem 1990;265:5952-5.
37. Zeng Q, Tran TT, Tan HX, Hong W. The cytoplasmic domain of Vamp4 and Vamp5 is responsible for their correct subcellular targeting: the N-terminal extenSion of VAMP4 contains a dominant autonomous targeting signal for the trans-Golgi network. J Biol Chem 2003;278:23046-54. (Pubitemid 36830370)
38. Bonifacino JS, Traub LM. Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 2003;72:395-447. (Pubitemid 36930451)
39. Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 2003;161:41-54. (Pubitemid 36459078)
40. Gould SJ, Keller GA, Hosken N, Wilkinson J, Subramani S. A conserved tripeptide sorts proteins to peroxisomes. J Cell Biol 1989;108:1657-64. (Pubitemid 19130498)
41. Cook A, Bono F, Jinek M, Conti E. Structural biology of nucleocytoplasmic transport. Annu Rev Biochem 2007;76:647-71.
42. Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, Corbett AH. Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem 2007;282:5101-5. (Pubitemid 47093710)
43. Lee BJ, Cansizoglu AE, Suel KE, Louis TH, Zhang Z, Chook YM. Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell 2006;126:543-58. (Pubitemid 44163605)
44. Xu D, Farmer A, Chook YM. Recognition of nuclear targeting signals by Karyopherin-beta proteins. Curr Opin Struct Biol 20:782-90.
45. Kutay U, Guttinger S. Leucine-rich nuclear-export signals: born to be weak. Trends Cell Biol 2005;15:121-4. (Pubitemid 40332533)
46. Turner JG, Engel R, Derderian JA, Jove R, Sullivan DM. Human topoisomerase IIalpha nuclear export is mediated by two CRM-1-dependent nuclear export signals. J Cell Sci 2004;117:3061-71. (Pubitemid 39117680)
47. Dong X, Biswas A, Suel KE, Jackson LK, Martinez R, Gu H, et al. Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature 2009;458:1136-41.
48. Matsuyama A, Arai R, Yashiroda Y, Shirai A, Kamata A, Sekido S, et al. ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol 2006;24:841-7. (Pubitemid 44086626)
49. Reichelt R, Holzenburg A, Buhle Jr EL, Jarnik M, Engel A, Aebi U. Correlation between structure and mass distribution of the nuclear pore complex and of distinct pore complex components. J Cell Biol 1990;110:883-94.
50. Lim RY, Aebi U, Fahrenkrog B. Towards reconciling structure and function in the nuclear pore complex. Histochem Cell Biol 2008;129:105-16.
51. Terry LJ, Shows EB, Wente SR. Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport. Science 2007;318:1412-6. (Pubitemid 350208921)
52. Arnaoutov A, Azuma Y, Ribbeck K, Joseph J, Boyarchuk Y, Karpova T, et al. Crm1 is a mitotic effector of Ran-GTP in somatic cells. Nat Cell Biol 2005;7:626-32. (Pubitemid 40796986)
53. Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J Cell Biol 2000;148:635-51.
54. Bednenko J, Cingolani G, Gerace L. Nucleocytoplasmic transport: navigating the channel. Traffic 2003;4:127-35. (Pubitemid 36621705)
55. Guttler T, Gorlich D. Ran-dependent nuclear export mediators: a structural perspective. Embo J 30:3457-74.
56. Weis K. The nuclear pore complex: oily spaghetti or gummy bear. Cell 2007;130:405-7. (Pubitemid 47198307)
57. Dong X, Biswas A, Chook YM. Structural basis for assembly and disassembly of the CRM1 nuclear export complex. Nat Struct Mol Biol 2009;16:558-60.
58. Monecke T, Guttler T, Neumann P, Dickmanns A, Gorlich D, Ficner R. Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP. Science 2009;324:1087-91.
59. Daelemans D, Costes SV, Lockett S, Kinetic Pavlakis GN. molecular analysis of nuclear export factor CRM1 association with its cargo in vivo. Mol Cell Biol 2005;25:728-39. (Pubitemid 40096593)
60. Yoneda Y, Hieda M, Nagoshi E, Miyamoto Y. Nucleocytoplasmic protein transport and recycling of Ran. Cell Struct Funct 1999;24:425-33. (Pubitemid 30128949)
61. Black BE, Holaska JM, Levesque L, Ossareh-Nazari B, Gwizdek C, Dargemont C, et al. NXT1 is necessary for the terminal step of Crm1-mediated nuclear export. J Cell Biol 2001;152:141-55. (Pubitemid 32102443)
62. Vogt PK, Jiang H, Aoki M. Triple layer control: phosphorylation, acetylation and ubiquitination of FOXO proteins. Cell Cycle 2005;4:908-13. (Pubitemid 41359756)
63. Craig E, Zhang ZK, Davies KP, Kalpana GV. A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis. Embo J 2002;21:31-42. (Pubitemid 34087072)
64. Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, et al. APC mutations occur early during colorectal tumorigenesis. Nature 1992;359:235-7.
65. Pichler A, Melchior F. Ubiquitin-related modifier SUMO1 and nucleocytoplasmic transport. Traffic 2002;3:381-7. (Pubitemid 34746405)
66. Poon IK, Jans DA. Regulation of nuclear transport: central role in development and transformation. Traffic 2005;6:173-86. (Pubitemid 40298152)
67. Hamamoto T, Seto H, Beppu T. Leptomycins A and B, new antifungal antibiotics. II. Structure elucidation. J Antibiot (Tokyo) 1983;36:646-50. (Pubitemid 13067621)
68. Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner EP, Wolff B, et al. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci U S A 1999;96:9112-7. (Pubitemid 29374716)
69. Mutka SC, Yang WQ, Dong SD, Ward SL, Craig DA, Timmermans PB, et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Res 2009;69:510-7.
70. Newlands ES, Rustin GJ, Phase Brampton MH. I trial of elactocin. Br J Cancer 1996;74:648-9.
71. Kalesse M, Christmann M, Bhatt U, Quitschalle M, Claus E, Saeed A, et al. The chemistry and biology of ratjadone. Chembiochem 2001;2:709-14. (Pubitemid 33722624)
72. Koster M, Lykke-Andersen S, Elnakady YA, Gerth K, Washausen P, Hofle G, et al. Ratjadones inhibit nuclear export by blocking CRM1/exportin 1. Exp Cell Res 2003;286:321-31. (Pubitemid 36566444)
73. Meissner T, Krause E, Ratjadone Vinkemeier U, leptomycin. B block CRM1-dependent nuclear export by identical mechanisms. FEBS Lett 2004;576:27-30. (Pubitemid 39330451)
74. Burzlaff A, Kalesse M, Kasper C, Scheper T. Multi parameter in vitro testing of ratjadone using flow cytometry. Appl Microbiol Biotechnol 2003;62:174-9. (Pubitemid 36995169)
75. Daelemans D, Afonina E, Nilsson J, Werner G, Kjems J, De Clercq E, et al. A synthetic HIV-1 Rev inhibitor interfering with the CRM1-mediated nuclear export. Proc Natl Acad Sci U S A 2002;99:14440-5. (Pubitemid 35257690)
76. Murakami N, Ye Y, Kawanishi M, Aoki S, Kudo N, Yoshida M, et al. New Rev-transport inhibitor with anti-HIV activity from Valerianae Radix. Bioorg Med Chem Lett 2002;12:2807-10. (Pubitemid 35266738)
77. Tamura S, Shiomi A, Kaneko M, Ye Y, Yoshida M, Yoshikawa M, et al. New Rev-export inhibitor from Alpinia galanga and structure-activity relationship. Bioorg Med Chem Lett 2009;19:2555-7.
78. Tamura S, Shimizu N, Fujiwara K, Kaneko M, Kimura T, Murakami N. Bioisostere of valtrate, anti-HIV principle by inhibition for nuclear export. Rev Bioorg Med Chem Lett 2010;20:2159-62.
79. Kau TR, Schroeder F, Ramaswamy S, Wojciechowski CL, Zhao JJ, Roberts TM, et al. A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells. Cancer Cell 2003;4:463-76. (Pubitemid 38050043)
80. Nakamura N, Ramaswamy S, Vazquez F, Signoretti S, Loda M, Sellers WR. Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN. Mol Cell Biol 2000;20:8969-82. (Pubitemid 32245927)
81. Sakakibara K, Saito N, Sato T, Suzuki A, Hasegawa Y, Friedman JM, et al. CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity. Blood 2011;118:3922-31.
82. Draetta GF, Shacham S, Kauffman M, Sandanayaka V, Schechter S, Williams JC, et al. Cytotoxicity of novel, small molecule, CRM1-selective inhibitors of nuclear export (SINE) in colorectal cancer (CRC) cells. J Clin Oncol 2011;29:Abstract e14091.
83. Shacham S, Turner JG, Nir R, Draetta G, Sandanayaka V, Shechter S, et al. Preclinical development of small-molecule CRM1 inhibitors as novel therapy for the treatment of myeloma and other hematological malignancies. Blood (ASH Annual Meeting Abstracts) 2010;116:Abstract 3012.
84. Noske A, Weichert W, Niesporek S, Roske A, Buckendahl AC, Koch I, et al. Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer. Cancer 2008;112:1733-43. (Pubitemid 351536833)
85. Huang WY, Yue L, Qiu WS, Wang LW, Zhou XH, Sun YJ. Prognostic value of CRM1 in pancreas cancer. Clin Invest Med 2009;32:E315.
86. Yao Y, Dong Y, Lin F, Zhao H, Shen Z, Chen P, et al. The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncol Rep 2009;21:229-35.
87. Shen A, Wang Y, Zhao Y, Zou L, Sun L, Cheng C. Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis. Neurosurgery 2009;65:153-9 [discussion 9-60].
88. van der Watt PJ, Maske CP, Hendricks DT, Parker MI, Denny L, Govender D, et al. The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer 2009;124:1829-40.
89. Karpa KD, Lin R, Kabbani N, Levenson R. The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf: D3-D3nf interaction causes mislocalization of D3 receptors. Mol Pharmacol 2000;58:677-83.
90. Edwards SW, Tan CM, Limbird LE. Localization of G-protein-coupled receptors in health and disease. Trends Pharmacol Sci 2000;21:304-8. (Pubitemid 30642920)
91. Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 1993;73:1251-4. (Pubitemid 23201140)
92. Davis JR, Kakar M, Lim CS. Controlling protein compartmentalization to overcome disease. Pharm Res 2007;24:17-27. (Pubitemid 44902566)
93. Turner JG, Sullivan DM. CRM1-mediated nuclear export of proteins and drug resistance in cancer. Curr Med Chem 2008;15:2648-55.
94. Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 2002;3:430-40. (Pubitemid 34685700)
95. Robinson MJ, Osheroff N. Effects of antineoplastic drugs on the post-strand-passage DNA cleavage/religation equilibrium of topoisomerase II. Biochemistry 1991;30:1807-13.
96. Valkov NI, Sullivan DM. Drug resistance to DNA topoisomerase I and II inhibitors in human leukemia, lymphoma, and multiple myeloma. Semin Hematol 1997;34:48-62. (Pubitemid 28032420)
97. Engel R, Valkov NI, Gump JL, Hazlehurst L, Dalton WS, Sullivan DM. The cytoplasmic trafficking of DNA topoisomerase IIalpha correlates with etoposide resistance in human myeloma cells. Exp Cell Res 2004;295:421-31. (Pubitemid 38490496)
98. Krzeslak A, Lipinska A. Galectin-3 as a multifunctional protein. Cell Mol Biol Lett 2004;9:305-28. (Pubitemid 38902225)
99. Matarrese P, Fusco O, Tinari N, Natoli C, Liu FT, Semeraro ML, et al. Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties. Int J Cancer 2000;85:545-54. (Pubitemid 30075135)
100. Honjo Y, Hrycyna CA, Yan QW, Medina-Perez WY, Robey RW, van de Laar A, et al. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res 2001;61:6635-9. (Pubitemid 32896477)
101. Perillo NL, Marcus ME, Baum LG. Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death. J Mol Med (Berl) 1998;76:402-12. (Pubitemid 28218642)
102. Park JW, Voss PG, Grabski S, Wang JL, Patterson RJ. Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the SMN protein. Nucleic Acids Res 2001;29:3595-602. (Pubitemid 32898773)
103. Lotz MM, Andrews Jr CW, Korzelius CA, Lee EC, Steele Jr GD, Clarke A, et al. Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc Natl Acad Sci U S A 1993;90:3466-70. (Pubitemid 23111387)
104. van den Brule FA, Waltregny D, Liu FT, Castronovo V. Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates with prostate carcinoma progression. Int J Cancer 2000;89:361-7. (Pubitemid 30620290)
105. Honjo Y, Nangia-Makker P, Inohara H, Raz A. Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells. Clin Cancer Res 2001;7:661-8. (Pubitemid 32707992)
106. Joo HG, Goedegebuure PS, Sadanaga N, Nagoshi M, von Bernstorff W, Eberlein TJ. Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes. J Leukocyte Biol 2001;69:555-64. (Pubitemid 32294840)
107. Fukumori T, Takenaka Y, Oka N, Yoshii T, Hogan V, Inohara H, et al. Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways. Cancer Res 2004;64:3376-9. (Pubitemid 38657907)
108. Takenaka Y, Fukumori T, Yoshii T, Oka N, Inohara H, Kim HR, et al. Nuclear export of phosphorylated galectin-3 regulates its antiapoptotic activity in response to chemotherapeutic drugs. Mol Cell Biol 2004;24:4395-406. (Pubitemid 41071009)
109. Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer 2005;5:172-83. (Pubitemid 40314949)
110. Skorski T, Bellacosa A, Nieborowska-Skorska M, Majewski M, Martinez R, Choi JK, et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. Embo J 1997;16:6151-61. (Pubitemid 27458335)
111. Vigneri P, Wang JY. Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med 2001;7:228-34. (Pubitemid 32148491)
112. Aloisi A, Di Gregorio S, Stagno F, Guglielmo P, Mannino F, Sormani MP, et al. BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B. Blood 2006;107:1591-8. (Pubitemid 43242398)
113. Kau TR, Way JC, Silver PA. Nuclear transport and cancer: from mechanism to intervention. Nat Rev Cancer 2004;4:106-17. (Pubitemid 38198739)
114. Jiao W, Datta J, Lin HM, Dundr M, Rane SG. Nucleocytoplasmic shuttling of the retinoblastoma tumor suppressor protein via Cdk phosphorylation-dependent nuclear export. J Biol Chem 2006;281:38098-108. (Pubitemid 46042113)
115. Senda T, Iizuka-Kogo A, Onouchi T, Shimomura A. Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. Med Mol Morphol 2007;40:68-81. (Pubitemid 47305230)
116. Neufeld KL, Nix DA, Bogerd H, Kang Y, Beckerle MC, Cullen BR, et al. Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm. Proc Natl Acad Sci U S A 2000;97:12085-90.
117. Rosin-Arbesfeld R, Cliffe A, Brabletz T, Bienz M. Nuclear export of the APC tumour suppressor controls beta-catenin function in transcription. Embo J 2003;22:1101-13. (Pubitemid 36313594)
118. Nikolaev AY, Li M, Puskas N, Qin J, Gu W. Parc: a cytoplasmic anchor for p53. Cell 2003;112:29-40. (Pubitemid 36106416)
119. Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC. Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res 2002;274:246-53.
120. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. Embo J 1999;18:1660-72. (Pubitemid 29127078)
121. Zhang Y, Xiong Y. A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 2001;292:1910-5. (Pubitemid 32538366)
122. O'Brate A, Giannakakou P. The importance of p53 location: nuclear or cytoplasmic zip code. Drug Resist Update 2003;6:313-22. (Pubitemid 38173582)
123. Rodriguez JA, Henderson BR. Identification of a functional nuclear export sequence in BRCA1. J Biol Chem 2000;275:38589-96. (Pubitemid 32009187)
124. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol 2001;3:245-52. (Pubitemid 32201319)
125. Asada M, Yamada T, Ichijo H, Delia D, Miyazono K, Fukumuro K, et al. Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation. Embo J 1999;18:1223-34. (Pubitemid 29110307)
126. Hwang CY, Kim IY, Kwon KS. Cytoplasmic localization and ubiquitination of p21(Cip1) by reactive oxygen species. Biochem Biophys Res Commun 2007;358:219-25. (Pubitemid 46719106)
127. Rodriguez-Vilarrupla A, Jaumot M, Abella N, Canela N, Brun S, Diaz C, et al. Binding of calmodulin to the carboxy-terminal region of p21 induces nuclear accumulation via inhibition of protein kinase C-mediated phosphorylation of Ser153. Mol Cell Biol 2005;25:7364-74. (Pubitemid 41105931)
128. Keeshan K, Cotter TG, McKenna SL. Bcr-Abl upregulates cytosolic p21WAF-1/CIP-1 by a phosphoinositide-3-kinase (PI3 K)-independent pathway. Br J Haematol 2003;123:34-44. (Pubitemid 37222755)
129. Danks MK, Garrett KE, Marion RC, Whipple DO. Subcellular redistribution of DNA topoisomerase I in anaplastic astrocytoma cells treated with topotecan. Cancer Res 1996;56:1664-73. (Pubitemid 26104033)
130. Santos A, Calvet L, Terrier-Lacombe MJ, Larsen A, Benard J, Pondarre C, et al. In vivo treatment with CPT-11 leads to differentiation of neuroblastoma xenografts and topoisomerase I alterations. Cancer Res 2004;64:3223-9. (Pubitemid 38581426)
131. Oloumi A, MacPhail SH, Johnston PJ, Banath JP, Olive PL. Changes in subcellular distribution of topoisomerase IIalpha correlate with etoposide resistance in multicell spheroids and xenograft tumors. Cancer Res 2000;60:5747-53.
132. Susaki E, Nakayama KI. Multiple mechanisms for p27(Kip1) translocation and degradation. Cell Cycle 2007;6:3015-20.
133. Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K, Nakayama KI. Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. J Biol Chem 2002;277:14355-8. (Pubitemid 34952496)
134. Foster JS, Fernando RI, Ishida N, Nakayama KI, Wimalasena J. Estrogens down-regulate p27Kip1 in breast cancer cells through Skp2 and through nuclear export mediated by the ERK pathway. J Biol Chem 2003;278:41355-66. (Pubitemid 37280965)
135. Shin I, Rotty J, Wu FY, Arteaga CL. Phosphorylation of p27Kip1 at Thr-157 interferes with its association with importin alpha during G1 and prevents nuclear re-entry. J Biol Chem 2005;280:6055-63. (Pubitemid 40280089)
136. Min YH, Cheong JW, Kim JY, Eom JI, Lee ST, Hahn JS, et al. Cytoplasmic mislocalization of p27Kip1 protein is associated with constitutive phosphorylation of Akt or protein kinase B and poor prognosis in acute myelogenous leukemia. Cancer Res 2004;64:5225-31. (Pubitemid 39006541)
137. Connor MK, Kotchetkov R, Cariou S, Resch A, Lupetti R, Beniston RG, et al. CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis. Mol Biol Cell 2003;14:201-13. (Pubitemid 36106030)
138. Haudek KC, Spronk KJ, Voss PG, Patterson RJ, Wang JL, Arnoys EJ. Dynamics of galectin-3 in the nucleus and cytoplasm. Biochim Biophys Acta 2010;1800:181-9.
139. Bartholomeusz G, Wu Y, Ali Seyed M, Xia W, Kwong KY, Hortobagyi G, et al. Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces apoptosis. Mol Carcinogen 2006;45:73-83. (Pubitemid 43204507)
140. Wang WS, Zhong HJ, Xiao DW, Huang X, Liao LD, Xie ZF, et al. The expression of CFL1 and N-WASP in esophageal squamous cell carcinoma and its correlation with clinicopathological features. Dis Esophagus 2010;23:512-21.
141. Sanchez AM, Flamini MI, Baldacci C, Goglia L, Genazzani AR, Simoncini T. Estrogen receptor-alpha promotes breast cancer cell motility and invasion via focal adhesion kinase and N-WASP. Mol Endocrinol 2010;24:2114-25.
142. Bourguignon LY, Peyrollier K, Gilad E, Brightman A. Hyaluronan-CD44 interaction with neural Wiskott-Aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to beta-catenin nuclear translocation, transcriptional up-regulation, and cell migration in ovarian tumor cells. J Biol Chem 2007;282:1265-80. (Pubitemid 47076574)
143. Falini B, Gionfriddo I, Cecchetti F, Ballanti S, Pettirossi V, Martelli MP. Acute myeloid leukemia with mutated nucleophosmin (NPM1): Any hope for a targeted therapy? Blood Rev 2011;25:247-54.
144. Karhemo PR, Rivinoja A, Lundin J, Hyvonen M, Chernenko A, Lammi J, et al. An extensive tumor array analysis supports tumor suppressive role for nucleophosmin in breast cancer. Am J Pathol 2011;179:1004-14.
145. Khandelwal N, Simpson J, Taylor G, Rafique S, Whitehouse A, Hiscox J, et al. Nucleolar NF-kappaB/RelA mediates apoptosis by causing cytoplasmic relocalization of nucleophosmin. Cell Death Differ 2011;18:1889-903.
146. Falini B, Bolli N, Shan J, Martelli MP, Liso A, Pucciarini A, et al. Both carboxyterminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML. Blood 2006;107:4514-23. (Pubitemid 43801380)
147. Diehl MC, Idowu MO, Kimmelshue K, York TP, Elmore LW, Holt SE. Elevated expression of nuclear Hsp90 in invasive breast tumors. Cancer Biol Ther 2009;8:1952-61.
148. Castoria G, Migliaccio A, Giovannelli P, Auricchio F. Cell proliferation regulated by estradiol receptor: Therapeutic implications. Steroids 2010;75:524-7.
149. Castoria G, Migliaccio A, Auricchio F. Signaling-dependent nuclear export of estradiol receptor controls cell cycle progression in breast cancer cells. Mol Cell Endocrinol 2009;308:26-31.
150. Maekawa M, Yamamoto T, Nishida E. Regulation of subcellular localization of the antiproliferative protein Tob by its nuclear export signal and bipartite nuclear localization signal sequences. Exp Cell Res 2004;295:59-65. (Pubitemid 38407345)
151. O'Malley S, Su H, Zhang T, Ng C, Ge H, Tang CK. TOB suppresses breast cancer tumorigenesis. Int J Cancer 2009;125:1805-13.
152. Kumari G, Mahalingam S. Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2. Exp Cell Res 2009;315:2775-90.
153. Muranen T, Gronholm M, Renkema GH, Carpen O. Cell cycle-dependent nucleocytoplasmic shuttling of the neurofibromatosis 2 tumour suppressor merlin. Oncogene 2005;24:1150-8. (Pubitemid 40313917)