Inhibition of the nuclear transporter, Kpnß1, results in prolonged mitotic arrest and activation of the intrinsic apoptotic pathway in cervical cancer cells

Carcinogenesis

Volumn 35, Issue 5, 2014, Pages 1121-1131

  Angus, Liselotte ^a   Van der Watt, Pauline J ^a   Leaner, Virna D ^a  

^a UNIVERSITY OF CAPE TOWN   (South Africa)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CASPASE 7; CYCLOHEXIMIDE; CYTOCHROME C; KARYOPHERIN BETA; KARYOPHERIN BETA1; PROTEIN BAX; PROTEIN BCL 2; PROTEIN E6; PROTEIN E7; PROTEIN MCL 1; PROTEIN NOXA; PROTEIN P53; RETINOBLASTOMA PROTEIN; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CELL CYCLE PROGRESSION; CELL DEATH; CELL FRACTIONATION; CELL PROLIFERATION; CELL SURVIVAL; CELL SYNCHRONIZATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; DNA DAMAGE; DOWN REGULATION; FEMALE; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; IMMUNOBLOTTING; MEMBRANE PERMEABILITY; MITOCHONDRIAL MEMBRANE; MITOSIS INHIBITION; MITOSIS SPINDLE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; UTERINE CERVIX CANCER; WESTERN BLOTTING;

APOPTOSIS; BETA KARYOPHERINS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; FEMALE; GENE KNOCKDOWN TECHNIQUES; HELA CELLS; HUMANS; MEMBRANE POTENTIAL, MITOCHONDRIAL; MITOSIS; MODELS, BIOLOGICAL; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53; UTERINE CERVICAL NEOPLASMS;

EID: 84902008352     PISSN: 01433334     EISSN: 14602180     Source Type: Journal    
DOI: 10.1093/carcin/bgt491     Document Type: Article

References (47)

1. Nakielny, S. et al. (1999) Transport of proteins and RNAs in and out of the nucleus. Cell, 99, 677-690.
2. Harel, A. et al. (2004) Importin beta: conducting a much larger cellular symphony. Mol. Cell, 16, 319-330.
3. Mitrousis, G. et al. (2008) Molecular basis for the recognition of snurportin 1 by importin beta. J. Biol. Chem., 283, 7877-7884.
4. Jäkel, S. et al. (1999) The importin beta/importin 7 heterodimer is a functional nuclear import receptor for histone H1. EMBO J., 18, 2411-2423.
5. Jullien, D. et al. (1999) Nuclear import of RPA in Xenopus egg extracts requires a novel protein XRIPalpha but not importin alpha. EMBO J., 18, 4348-4358.
6. Chook, Y.M. et al. (2001) Karyopherins and nuclear import. Curr. Opin. Struct. Biol., 11, 703-715.
7. Mosammaparast, N. et al. (2004) Karyopherins: from nuclear-transport mediators to nuclear-function regulators. Trends Cell Biol., 14, 547-556.
8. Ciciarello, M. et al. (2004) Importin beta is transported to spindle poles during mitosis and regulates Ran-dependent spindle assembly factors in mammalian cells. J. Cell Sci., 117, 6511-6522.
9. Roscioli, E. et al. (2012) Importin-ß negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores. J. Cell Biol., 196, 435-450.
10. Kau, T.R. et al. (2003) Nuclear transport as a target for cell growth. Drug Discov. Today, 8, 78-85.
11. Kau, T.R. et al. (2004) Nuclear transport and cancer: from mechanism to intervention. Nat. Rev. Cancer, 4, 106-117.
12. Yashiroda, Y. et al. (2003) Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs. Curr. Med. Chem., 10, 741-748.
13. van der Watt, P.J. et al. (2013) The nuclear import receptor Kpnß1 and its potential as an anticancer therapeutic target. Crit. Rev. Eukaryot. Gene Expr., 23, 1-10.
14. van der Watt, P.J. et al. (2009) The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int. J. Cancer, 124, 1829-1840.
15. van der Watt, P.J. et al. (2011) Overexpression of Kpnß1 and Kpna2 importin proteins in cancer derives from deregulated E2F activity. PLoS One, 6, e27723.
16. Scheffner, M. et al. (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell, 63, 1129-1136.
17. Chellappan, S. et al. (1992) Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc. Natl Acad. Sci. USA, 89, 4549-4553.
18. Smith, E.R. et al. (2010) Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells. PLoS One, 5, e9295.
19. Kuusisto, H.V. et al. (2012) Global enhancement of nuclear localizationdependent nuclear transport in transformed cells. FASEB J., 26, 1181-1193.
20. van der Westhuizen, D.R. et al. (1984) Low density lipoprotein receptor mutations in South African homozygous familial hypercholesterolemic patients. Arterioscler. Thromb., 4, 238-247.
21. Harley, M.E. et al. (2010) Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J., 29, 2407-2420.
22. Warr, M.R. et al. (2011) Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site. J. Biol. Chem., 286, 25098-25107.
23. Nijhawan, D. et al. (2003) Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes Dev., 17, 1475-1486.
24. Oda, E. et al. (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science, 288, 1053-1058.
25. Hubbert, N.L. et al. (1992) Human papillomavirus type 16 E6 increases the degradation rate of p53 in human keratinocytes. J. Virol., 66, 6237-6241.
26. Talis, A.L. et al. (1998) The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells. J. Biol. Chem., 273, 6439-6445.
27. Zhang, G. et al. (2009) HPV-16E6 can induce multiple site phosphorylation of p53. Oncol. Rep., 21, 371-377.
28. Nachury, M.V. et al. (2001) Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. Cell, 104, 95-106.
29. Güttinger, S. et al. (2009) Orchestrating nuclear envelope disassembly and reassembly during mitosis. Nat. Rev. Mol. Cell Biol., 10, 178-191.
30. Gruss, O.J. et al. (2001) Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. Cell, 104, 83-93.
31. Wiese, C. et al. (2001) Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. Science, 291, 653-656.
32. Ems-McClung, S.C. et al. (2004) Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal. Mol. Biol. Cell, 15, 46-57.
33. Ryan, K.J. et al. (2007) The karyopherin Kap95 regulates nuclear pore complex assembly into intact nuclear envelopes in vivo. Mol. Biol. Cell, 18, 886-898.
34. Schmitz, M.H. et al. (2010) Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells. Nat. Cell Biol., 12, 886-893.
35. Nomura, M. et al. (1999) Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res., 59, 5542-5548.
36. Eskes, R. et al. (2000) Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol. Cell. Biol., 20, 929-935.
37. Suzuki, M. et al. (2000) Structure of Bax: coregulation of dimer formation and intracellular localization. Cell, 103, 645-654.
38. Antonsson, B. (2001) Bax and other pro-apoptotic Bcl-2 family "killerproteins" and their victim the mitochondrion. Cell Tissue Res., 306, 347-361.
39. Inuzuka, H. et al. (2011) Mcl-1 ubiquitination and destruction. Oncotarget, 2, 239-244.
40. Wertz, I.E. et al. (2011) Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature, 471, 110-114.
41. Evan, G.I. et al. (2001) Proliferation, cell cycle and apoptosis in cancer. Nature, 411, 342-348.
42. Qin, J.Z. et al. (2004) p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas. Mol. Cancer Ther., 3, 895-902.
43. Armstrong, J.L. et al. (2007) Role of Noxa in p53-independent fenretinideinduced apoptosis of neuroectodermal tumours. Apoptosis, 12, 613-622.
44. Marchenko, N.D. et al. (2010) Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-alpha3 binding. Cell Death Differ., 17, 255-267.
45. Scheffner, M. et al. (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell, 75, 495-505.
46. Stewart, D. et al. (2005) Involvement of nuclear export in human papillomavirus type 18 E6-mediated ubiquitination and degradation of p53. J. Virol., 79, 8773-8783.
47. Le Roux, L.G. et al. (2003) Nuclear entry of high-risk human papillomavirus type 16 E6 oncoprotein occurs via several pathways. J. Virol., 77, 2330-2337.