Identification of a small molecule inhibitor of importin β mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries

ACS Chemical Biology

Volumn 5, Issue 10, 2010, Pages 967-979

  Hintersteiner, Martin ^a,c   Ambrus, Géza ^b   Bednenko, Janna ^b   Schmied, Mario ^c   Knox, Andrew J S ^a   Meisner, Nicole Claudia ^c   Gstach, Hubert ^c   Seifert, Jan Marcus ^c   Singer, Eric L ^b   Gerace, Larry ^b   Auer, Manfred ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c Novartis Institutes for BioMedical Research (NIBR)   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

EXPORTIN 1; GREEN FLUORESCENT PROTEIN; KARYOPHERIN ALPHA; KARYOPHERIN BETA; KARYOSTATIN 1A; PROTEIN INHIBITOR; RAN PROTEIN; TRANSCRIPTION FACTOR NFAT; UNCLASSIFIED DRUG;

ARTICLE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; HELA CELL; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULAR LIBRARY; MOLECULAR MODEL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; STRUCTURE ACTIVITY RELATION; SURFACE PLASMON RESONANCE;

ACTIVE TRANSPORT, CELL NUCLEUS; BETA KARYOPHERINS; DRUG EVALUATION, PRECLINICAL; HELA CELLS; HUMANS; PROTEIN BINDING; RAN GTP-BINDING PROTEIN; SMALL MOLECULE LIBRARIES;

EUKARYOTA;

EID: 77958113414     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb100094k     Document Type: Article

References (36)

1. Terry, L. J., Shows, E. B., and Wente, S. R. (2007) Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport Science 318, 1412-1416
2. Stewart, M. (2007) Molecular mechanism of the nuclear protein import cycle Nat. Rev. Mol. Cell. Biol. 8, 195-208
3. Weis, K. (1998) Importins and exportins: how to get in and out of the nucleus Trends Biochem. Sci. 23, 185-189
4. Cook, A., Bono, F., Jinek, M., and Conti, E. (2007) Structural biology of nucleocytoplasmic transport Annu. Rev. Biochem. 76, 647-671
5. Bednenko, J., Cingolani, G., and Gerace, L. (2003) Nucleocytoplasmic transport: navigating the channel Traffic 4, 127-135
6. Gorlich, D., Henklein, P., Laskey, R. A., and Hartmann, E. (1996) A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus EMBO J. 15, 1810-1817
7. Lee, S. J., Matsuura, Y., Liu, S. M., and Stewart, M. (2005) Structural basis for nuclear import complex dissociation by RanGTP Nature 435, 693-696
8. Nachury, M. V. and Weis, K. (1999) The direction of transport through the nuclear pore can be inverted Proc. Natl. Acad. Sci. U.S.A. 96, 9622-9627
9. Hintersteiner, M., Buehler, C., Uhl, V., Schmied, M., Muller, J., Kottig, K., and Auer, M. (2009) Confocal nanoscanning, bead picking (CONA): PickoScreen microscopes for automated and quantitative screening of one-bead one-compound libraries J. Comb. Chem. 11, 886-894
10. Kudo, N., Wolff, B., Sekimoto, T., Schreiner, E. P., Yoneda, Y., Yanagida, M., Horinouchi, S., and Yoshida, M. (1998) Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1 Exp. Cell Res. 242, 540-547
11. Nishi, K., Yoshida, M., Fujiwara, D., Nishikawa, M., Horinouchi, S., and Beppu, T. (1994) Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression J. Biol. Chem. 269, 6320-6324
12. Kwon, Y.-J., Genovesio, A., Kim, N. Y., Kim, H. C., Jung, S., David-Watine, B., Nehrbass, U., and Emans, N. (2007) High-content classification of nucleocytoplasmic import or export inhibitors J. Biomol. Screening 12, 621-627
13. Wolff, B., Sanglier, J. J., and Wang, Y. (1997) Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA Chem. Biol. 4, 139-147
14. Yashiroda, Y. and Yoshida, M. (2003) Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs Curr. Med. Chem. 10, 741-748
15. Kau, T. R. and Silver, P. A. (2003) Nuclear transport as a target for cell growth Drug Discovery Today 8, 78-85
16. Kobayashi, T., Kamitani, W., Zhang, G., Watanabe, M., Tomonaga, K., and Ikuta, K. (2001) Borna disease virus nucleoprotein requires both nuclear localization and export activities for viral nucleocytoplasmic shuttling J. Virol. 75, 3404-3412
17. Kumar, S., Saradhi, M., Chaturvedi, N. K., and Tyagi, R. K. (2006) Intracellular localization and nucleocytoplasmic trafficking of steroid receptors: an overview Mol. Cell. Endocrinol. 246, 147-156
18. Van Neck, T., Pannecouque, C., Vanstreels, E., Stevens, M., Dehaen, W., and Daelemans, D. (2008) Inhibition of the CRM1-mediated nucleocytoplasmic transport by N-azolylacrylates: Structure-activity relationship and mechanism of action Bioorg. Med. Chem. 16, 9487-9497
19. Kosugi, S., Hasebe, M., Entani, T., Takayama, S., Tomita, M., and Yanagawa, H. (2008) Design of peptide inhibitors for the importin alpha /beta nuclear import pathway by activity-based profiling Chem. Biol. (Cambridge, MA, U. S.) 15, 940-949
20. Meisner, N. C., Hintersteiner, M., Uhl, V., Weidemann, T., Schmied, M., Gstach, H., and Auer, M. (2004) The chemical hunt for the identification of drugable targets Curr. Opin. Chem. Biol. 8, 424-431
21. Meisner, N.-C., Hintersteiner, M., Seifert, J.-M., Bauer, R., Benoit Roger, M., Widmer, A., Schindler, T., Uhl, V., Lang, M., Gstach, H., and Auer, M. (2009) Terminal adenosyl transferase activity of posttranscriptional regulator HuR revealed by confocal on-bead screening J. Mol. Biol. 386, 435-450
22. Hintersteiner, M. and Auer, M. (2008) Single-bead, single-molecule, single-cell fluorescence technologies for drug screening and target validation Ann. N. Y. Acad. Sci. 1130, 1-11
23. Hintersteiner, M., Kimmerlin, T., Kalthoff, F., Stoeckli, M., Garavel, G., Seifert, J.-M., Meisner, N.-C., Uhl, V., Buehler, C., Weidemann, T., and Auer, M. (2009) Single bead labeling method for combining confocal fluorescence on-bead screening and solution validation of tagged one-bead one-compound libraries Chem. Biol. (Cambridge, MA, U. S.) 16, 724-735
24. Muckenschnabel, I., Falchetto, R., Mayr, L. M., and Filipuzzi, I. (2004) /1/15) SpeedScreen: label-free liquid chromatography-mass spectrometry-based high-throughput screening for the discovery of orphan protein ligands Anal. Biochem. 324, 241-249
25. Melchior, F., Sweet, D. J., and Gerace, L. (1995) Analysis of Ran/TC4 function in nuclear protein import Methods Enzymol. 257, 279-291
26. Kehlenbach, R. H., Dickmanns, A., Kehlenbach, A., Guan, T., and Gerace, L. (1999) A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export J. Cell Biol. 145, 645-657
27. Kehlenbach, R. H., Dickmanns, A., and Gerace, L. (1998) Nucleocytoplasmic shuttling factors including Ran and CRM1 mediate nuclear export of NFAT In vitro J. Cell Biol. 141, 863-874
28. Bischoff, F. R. and Gorlich, D. (1997) RanBP1 is crucial for the release of RanGTP from importin beta-related nuclear transport factors FEBS Lett. 419, 249-254
29. Ben-Efraim, I. and Gerace, L. (2001) Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import J. Cell Biol. 152, 411-417
30. Mitrousis, G., Olia, A. S., Walker-Kopp, N., and Cingolani, G. (2008) Molecular basis for the recognition of snurportin 1 by importin beta J. Biol. Chem. 283, 7877-7884
31. Adam, S. A. and Gerace, L. (1991) Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import Cell 66, 837-847
32. Adam, E. J. and Adam, S. A. (1994) Identification of cytosolic factors required for nuclear location sequence-mediated binding to the nuclear envelope J. Cell Biol. 125, 547-555
33. Kutay, U., Izaurralde, E., Bischoff, F. R., Mattaj, I. W., and Gorlich, D. (1997) Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex EMBO J. 16, 1153-1163
34. Bednenko, J., Cingolani, G., and Gerace, L. (2003) Importin beta contains a COOH-terminal nucleoporin binding region important for nuclear transport J. Cell Biol. 162, 391-401
35. Melchior, F., Paschal, B., Evans, J., and Gerace, L. (1993) Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor J. Cell Biol. 123, 1649-1659
36. Cassany, A. and Gerace, L. (2009) Reconstitution of nuclear import in permeabilized cells Methods Mol. Biol. 464, 181-205