Identification of CRM1-dependent nuclear export cargos using quantitative mass spectrometry

Molecular and Cellular Proteomics

Volumn 12, Issue 3, 2013, Pages 664-678

  Thakar, Ketan ^a   Karaca, Samir ^b   Port, Sarah A ^a   Urlaub, Henning ^b,c   Kehlenbach, Ralph H ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b MAX PLANCK INSTITUTE FOR BIOPHYSICAL CHEMISTRY   (Germany)

^c UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CARBOXYPEPTIDASE; CYTOSOLIC CARBOXYPEPTIDASE 1; EXPORTIN 1; GUANINE NUCLEOTIDE BINDING PROTEIN; LAMIN A; LAMIN C; LEPTOMYCIN B; PHOSPHOPROTEIN PHOSPHATASE 2A; POLYUBIQUITIN; PROGRAMMED DEATH 1 LIGAND 2; PROTEOME; STABLE ISOTOPE; TRANSCRIPTION FACTOR SP1; UNCLASSIFIED DRUG;

ARTICLE; CELL CULTURE; CELL FRACTIONATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOSOLIC FRACTION; HUMAN; HUMAN CELL; ISOTOPE LABELING; MASS SPECTROMETRY; NUCLEAR EXPORT SIGNAL; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN STABILITY; RIBOSOME SUBUNIT; RNA PROCESSING; RNA SPLICING;

ACTIVE TRANSPORT, CELL NUCLEUS; ADAPTOR PROTEINS, SIGNAL TRANSDUCING; CARBOXYPEPTIDASES; CELL NUCLEUS; FATTY ACIDS, UNSATURATED; GTP-BINDING PROTEINS; HELA CELLS; HUMANS; IMMUNOBLOTTING; KARYOPHERINS; LUMINESCENT PROTEINS; MASS SPECTROMETRY; MICROSCOPY, CONFOCAL; MICROSCOPY, FLUORESCENCE; NUCLEAR EXPORT SIGNALS; PROTEIN BINDING; PROTEIN PHOSPHATASE 2; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECOMBINANT FUSION PROTEINS;

EID: 84874638077     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M112.024877     Document Type: Article

References (79)

1. Fernandez-Martinez, J., and Rout, M. P. (2012) A jumbo problem: Mapping the structure and functions of the nuclear pore complex. Curr. Opin. Cell Biol. 24, 92-99
2. Onischenko, E., and Weis, K. (2011) Nuclear pore complex-a coat specifically tailored for the nuclear envelope. Curr. Opin. Cell Biol. 23, 293-301
3. Fried, H., and Kutay, U. (2003) Nucleocytoplasmic transport: Taking an inventory. Cell. Mol. Life Sci. 60, 1659-1688 (Pubitemid 37041364)
4. Wente, S. R., and Rout, M. P. (2010) The nuclear pore complex and nuclear transport. Cold Spring Harb. Perspect. Biol. 2010, 10.1101/ cshperspect.a000562
5. Hutten, S., and Kehlenbach, R. H. (2007) CRM1-mediated nuclear export: To the pore and beyond. Trends Cell Biol. 17, 193-201 (Pubitemid 46507806)
6. Fischer, U., Huber, J., Boelens, W. C., Mattaj, I. W., and Luhrmann, R. (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82, 475-483
7. Wen, W., Meinkoth, J. L., Tsien, R. Y., and Taylor, S. S. (1995) Identification of a signal for rapid export of proteins from the nucleus. Cell 82, 463-473
8. Kutay, U., and Gu? ttinger, S. (2005) Leucine-rich nuclear-export signals: Born to be weak. Trends Cell Biol. 15, 121-124 (Pubitemid 40332533)
9. Guttler, T., Madl, T., Neumann, P., Deichsel, D., Corsini, L., Monecke, T., Ficner, R., Sattler, M., and Gorlich, D. (2010) NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1. Nat. Struct. Mol. Biol. 17, 1367-1376
10. Xu, D., Farmer, A., Collett, G., Grishin, N. V., and Chook, Y. M. (2012) Sequence and structural analyses of nuclear export signals in the NESdb database. Mol. Biol. Cell 23, 3677-3693
11. Xu, D., Grishin, N. V., and Chook, Y. M. (2012) NESdb: A database of NES-containing CRM1 cargos. Mol. Biol. Cell 23, 3673-3676
12. Engelsma, D., Bernad, R., Calafat, J., and Fornerod, M. (2004) Supraphysiological nuclear export signals bind CRM1 independently of RanGTP and arrest at Nup358. EMBO J. 23, 3643-3652 (Pubitemid 39336286)
13. Ayers, S. D., Nedrow, K. L., Gillilan, R. E., and Noy, N. (2007) Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPARgamma by FABP4. Biochemistry 46, 6744-6752 (Pubitemid 46906405)
14. Dong, X., Biswas, A., Suel, K. E., Jackson, L. K., Martinez, R., Gu, H., and Chook, Y. M. (2009) Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature 458, 1136-1141
15. Monecke, T., Guttler, T., Neumann, P., Dickmanns, A., Gorlich, D., and Ficner, R. (2009) Crystal structure of the nuclear export receptor CRM1in complex with Snurportin1 and RanGTP. Science 324, 1087-1091
16. Paraskeva, E., Izaurralde, E., Bischoff, F. R., Huber, J., Kutay, U., Hartmann, E., Luhrmann, R., and Gorlich, D. (1999) CRM1-mediated recycling of snurportin 1 to the cytoplasm. J. Cell Biol. 145, 255-264 (Pubitemid 29198299)
17. Fu, S. C., Imai, K., and Horton, P. (2011) Prediction of leucine-rich nuclear export signal containing proteins with NESsential. Nucleic Acids Res. 39, e111
18. la Cour, T., Kiemer, L., Molgaard, A., Gupta, R., Skriver, K., and Brunak, S. (2004) Analysis and prediction of leucine-rich nuclear export signals. Protein Eng. Des. Sel. 17, 527-536 (Pubitemid 39487532)
19. la Cour, T., Gupta, R., Rapacki, K., Skriver, K., Poulsen, F. M., and Brunak, S. (2003) NESbase version 1.0: A database of nuclear export signals. Nucleic Acids Res. 31, 393-396 (Pubitemid 36150410)
20. Kehlenbach, R. H., Assheuer, R., Kehlenbach, A., Becker, J., and Gerace, L. (2001) Stimulation of nuclear export and inhibition of nuclear import by a Ran mutant deficient in binding to Ran-binding protein 1. J. Biol. Chem. 276, 14524-14531
21. Mueller, L., Cordes, V. C., Bischoff, F. R., and Ponstingl, H. (1998) Human RanBP3, a group of nuclear RanGTP binding proteins. FEBS Lett. 427, 330-336 (Pubitemid 28244301)
22. Nemergut, M. E., Lindsay, M. E., Brownawell, A. M., and Macara, I. G. (2002) Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor. J. Biol. Chem. 277, 17385-17388 (Pubitemid 34967537)
23. Oka, M., Asally, M., Yasuda, Y., Ogawa, Y., Tachibana, T., and Yoneda, Y. (2010) The mobile FG nucleoporin Nup98 is a cofactor for Crm1-dependent protein export. Mol. Biol. Cell 21, 1885-1896
24. Waldmann, I., Spillner, C., and Kehlenbach, R. H. (2012) The nucleoporinlike protein NLP1 (hCG1) promotes CRM1-dependent nuclear protein export. J. Cell Sci. 125, 144-154
25. Hamamoto, T., Gunji, S., Tsuji, H., and Beppu, T. (1983) Leptomycins A and B, new antifungal antibiotics. I. Taxonomy of the producing strain and their fermentation, purification and characterization. J. Antibiot. (Tokyo) 36, 639-645 (Pubitemid 13067620)
26. Fornerod, M., Ohno, M., Yoshida, M., and Mattaj, I. W. (1997) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90, 1051-1060 (Pubitemid 27408519)
27. 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 (Pubitemid 27161752)
28. Kudo, N., Matsumori, N., Taoka, H., Fujiwara, D., Schreiner, E. P., Wolff, B., Yoshida, M., and Horinouchi, S. (1999) 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. 96, 9112-9117 (Pubitemid 29374716)
29. Charneau, P., Mirambeau, G., Roux, P., Paulous, S., Buc, H., and Clavel, F. (1994) HIV-1 reverse transcription. A termination step at the center of the genome. J. Mol. Biol. 241, 651-662
30. Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., and Struhl, K. (1994) Current Protocols in Molecular Biology, Greene Publishing Associates and Wiley-Interscience, New York
31. Holden, P., and Horton, W. A. (2009) Crude subcellular fractionation of cultured mammalian cell lines. BMC Res. Notes 2, 243
32. Hutten, S., Flotho, A., Melchior, F., and Kehlenbach, R. H. (2008) The Nup358-RanGAP complex is required for efficient importin alpha/betadependent nuclear import. Mol. Biol. Cell 19, 2300-2310
33. Gasteier, J. E., Madrid, R., Krautkramer, E., Schroder, S., Muranyi, W., Benichou, S., and Fackler, O. T. (2003) Activation of the Rac-binding partner FHOD1 induces actin stress fibers via a ROCK-dependent mechanism. J. Biol. Chem. 278, 38902-38912 (Pubitemid 37221790)
34. Shevchenko, A., Tomas, H., Havlis, J., Olsen, J. V., and Mann, M. (2006) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 1, 2856-2860
35. Cox, J., and Mann, M. (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367-1372
36. Huang, D. W., Sherman, B. T., and Lempicki, R. A. (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57
37. Szklarczyk, D., Franceschini, A., Kuhn, M., Simonovic, M., Roth, A., Minguez, P., Doerks, T., Stark, M., Muller, J., Bork, P., Jensen, L. J., and von Mering, C. (2011) The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39, D561-D568
38. Dinkel, H., Michael, S., Weatheritt, R. J., Davey, N. E., Van Roey, K., Altenberg, B., Toedt, G., Uyar, B., Seiler, M., Budd, A., Jodicke, L., Dammert, M. A., Schroeter, C., Hammer, M., Schmidt, T., Jehl, P., McGuigan, C., Dymecka, M., Chica, C., Luck, K., Via, A., Chatr-Aryamontri, A., Haslam, N., Grebnev, G., Edwards, R. J., Steinmetz, M. O., Meiselbach, H., Diella, F., and Gibson, T. J. (2012) ELM-the database of eukaryotic linear motifs. Nucleic Acids Res. 40, D242-D251
39. Hutten, S., and Kehlenbach, R. H. (2006) Nup214 is required for CRM1-dependent nuclear protein export in vivo. Mol. Cell. Biol. 26, 6772-6785 (Pubitemid 44387628)
40. Guan, T., Kehlenbach, R. H., Schirmer, E. C., Kehlenbach, A., Fan, F., Clurman, B. E., Arnheim, N., and Gerace, L. (2000) Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein export. Mol. Cell. Biol. 20, 5619-5630 (Pubitemid 30482896)
41. Melchior, F., Sweet, D. J., and Gerace, L. (1995) Analysis of Ran/TC4 function in nuclear protein import. Methods Enzymol. 257, 279-291
42. Pollard, V. W., Michael, W. M., Nakielny, S., Siomi, M. C., Wang, F., and Dreyfuss, G. (1996) A novel receptor-mediated nuclear protein import pathway. Cell 86, 985-994 (Pubitemid 26336802)
43. Biswas, A., Mukherjee, S., Das, S., Shields, D., Chow, C. W., and Maitra, U. (2011) Opposing action of casein kinase 1 and calcineurin in nucleocytoplasmic shuttling of mammalian translation initiation factor eIF6. J. Biol. Chem. 286, 3129-3138
44. Yedavalli, V. S., Neuveut, C., Chi, Y. H., Kleiman, L., and Jeang, K. T. (2004) Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 119, 381-392 (Pubitemid 39423840)
45. Ho, J. H., Kallstrom, G., and Johnson, A. W. (2000) Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit. J. Cell Biol. 151, 1057-1066
46. Kato, J. Y., and Yoneda-Kato, N. (2009) Mammalian COP9 signalosome. Genes Cells 14, 1209-1225
47. Tomoda, K., Kubota, Y., Arata, Y., Mori, S., Maeda, M., Tanaka, T., Yoshida, M., Yoneda-Kato, N., and Kato, J. Y. (2002) The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J. Biol. Chem. 277, 2302-2310 (Pubitemid 34968817)
48. Shin, J. (1998) P62 and the sequestosome, a novel mechanism for protein metabolism. Arch. Pharm. Res. 21, 629-633 (Pubitemid 128668388)
49. Geetha, T., Vishwaprakash, N., Sycheva, M., and Babu, J. R. (2012) Sequestosome 1/p62: Across diseases. Biomarkers 17, 99-103
50. Moscat, J., Diaz-Meco, M. T., and Wooten, M. W. (2007) Signal integration and diversification through the p62 scaffold protein. Trends Biochem. Sci. 32, 95-100 (Pubitemid 46199192)
51. Meng, L., Zhu, Q., and Tsai, R. Y. (2007) Nucleolar trafficking of nucleostemin family proteins: Common versus protein-specific mechanisms. Mol. Cell. Biol. 27, 8670-8682
52. Junttila, M. R., Puustinen, P., Niemela, M., Ahola, R., Arnold, H., Bottzauw, T., Ala-aho, R., Nielsen, C., Ivaska, J., Taya, Y., Lu, S. L., Lin, S., Chan, E. K., Wang, X. J., Grenman, R., Kast, J., Kallunki, T., Sears, R., Kahari, V. M., and Westermarck, J. (2007) CIP2A inhibits PP2A in human malignancies. Cell 130, 51-62 (Pubitemid 47039258)
53. Harris, A., Morgan, J. I., Pecot, M., Soumare, A., Osborne, A., and Soares, H. D. (2000) Regenerating motor neurons express Nna1, a novel ATP/ GTP-binding protein related to zinc carboxypeptidases. Mol. Cell. Neurosci. 16, 578-596 (Pubitemid 32001307)
54. Rogowski, K., van Dijk, J., Magiera, M. M., Bosc, C., Deloulme, J. C., Bosson, A., Peris, L., Gold, N. D., Lacroix, B., Grau, M. B., Bec, N., Larroque, C., Desagher, S., Holzer, M., Andrieux, A., Moutin, M. J., and Janke, C. (2010) A family of protein-deglutamylating enzymes associated with neurodegeneration. Cell 143, 564-578
55. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., and Mann, M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834-840
56. Golebiowski, F., Matic, I., Tatham, M. H., Cole, C., Yin, Y., Nakamura, A., Cox, J., Barton, G. J., Mann, M., and Hay, R. T. (2009) System-wide changes to SUMO modifications in response to heat shock. Sci. Signal 2, ra24
57. Olsen, J. V., Vermeulen, M., Santamaria, A., Kumar, C., Miller, M. L., Jensen, L. J., Gnad, F., Cox, J., Jensen, T. S., Nigg, E. A., Brunak, S., and Mann, M. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal 3, ra3
58. Schwanhausser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., and Selbach, M. (2011) Global quantification of mammalian gene expression control. Nature 473, 337-342
59. Boisvert, F. M., Ahmad, Y., Gierlinski, M., Charriere, F., Lamont, D., Scott, M., Barton, G., and Lamond, A. I. (2012) A quantitative spatial proteomics analysis of proteome turnover in human cells. Mol. Cell. Proteomics 11, M111.011429
60. Wild, T., Horvath, P., Wyler, E., Widmann, B., Badertscher, L., Zemp, I., Kozak, K., Csucs, G., Lund, E., and Kutay, U. (2010) A protein inventory of human ribosome biogenesis reveals an essential function of exportin 5 in 60S subunit export. PLoS 8, e1000522
61. Sanchez, P., De Carcer, G., Sandoval, I. V., Moscat, J., and Diaz-Meco, M. T. (1998) Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62. Mol. Cell. Biol. 18, 3069-3080 (Pubitemid 28183475)
62. Wooten, M. W., Geetha, T., Seibenhener, M. L., Babu, J. R., Diaz-Meco, M. T., and Moscat, J. (2005) The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J. Biol. Chem. 280, 35625-35629 (Pubitemid 41532755)
63. Perander, M., Bjorkoy, G., and Johansen, T. (2001) Nuclear import and export signals enable rapid nucleocytoplasmic shuttling of the atypical protein kinase C lambda. J. Biol. Chem. 276, 13015-13024
64. Johnson, C., Van Antwerp, D., and Hope, T. J. (1999) An N-terminal nuclear export signal is required for the nucleocytoplasmic shuttling of IkappaBalpha. EMBO J. 18, 6682-6693
65. Flegg, C. P., Sharma, M., Medina-Palazon, C., Jamieson, C., Galea, M., Brocardo, M. G., Mills, K., and Henderson, B. R. (2010) Nuclear export and centrosome targeting of the protein phosphatase 2A subunit B56alpha: Role of B56alpha in nuclear export of the catalytic subunit. J. Biol. Chem. 285, 18144-18154
66. Inoue, H., Kauffman, M., Shacham, S., Landesman, Y., Yang, J., Evans, C. P., and Weiss, R. H. (2012) CRM1 blockade by selective inhibitors of nuclear export (SINE) attenuates kidney cancer growth. J Urol. (in press)
67. Ranganathan, P., Yu, X., Na, C., Santhanam, R., Shacham, S., Kauffman, M., Walker, A., Klisovic, R., Blum, W., Caligiuri, M., Croce, C. M., Marcucci, G., and Garzon, R. (2012) Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood 120, 1765-1773
68. Kimura, M., Kose, S., Okumura, N., Imai, K., Furuta, M., Sakiyama, N., Tomii, K., Horton, P., Takao, T., and Imamoto, N. (2012) Identification of cargo proteins specific for the nucleocytoplasmic transport carrier transportin by combination of an in vitro transport system and SILAC-based quantitative proteomics. Mol. Cell. Proteomics (in press)
69. Walde, S., Thakar, K., Hutten, S., Spillner, C., Nath, A., Rothbauer, U., Wiemann, S., and Kehlenbach, R. H. (2012) The nucleoporin Nup358/ RanBP2 promotes nuclear import in a cargo-and transport receptorspecific manner. Traffic 13, 218-233
70. Miki, T., Okawa, K., Sekimoto, T., Yoneda, Y., Watanabe, S., Ishizaki, T., and Narumiya, S. (2009) mDia2 shuttles between the nucleus and the cytoplasm through the importin-{alpha}/{beta}-and CRM1-mediated nuclear transport mechanism. J. Biol. Chem. 284, 5753-5762
71. Huang, T. T., Kudo, N., Yoshida, M., and Miyamoto, S. (2000) A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes. Proc. Natl. Acad. Sci. U.S.A. 97, 1014-1019 (Pubitemid 30080804)
72. Seiser, R. M., Sundberg, A. E., Wollam, B. J., Zobel-Thropp, P., Baldwin, K., Spector, M. D., and Lycan, D. E. (2006) Ltv1 is required for efficient nuclear export of the ribosomal small subunit in Saccharomyces cerevisiae. Genetics 174, 679-691 (Pubitemid 44656459)
73. Toyoshima, F., Moriguchi, T., Wada, A., Fukuda, M., and Nishida, E. (1998) Nuclear export of cyclin B1 and its possible role in the DNA damageinduced G2 checkpoint. EMBO J. 17, 2728-2735 (Pubitemid 28227119)
74. Harhaj, E. W., and Sun, S. C. (1999) Regulation of RelA subcellular localization by a putative nuclear export signal and p50. Mol. Cell. Biol. 19, 7088-7095 (Pubitemid 29441890)
75. Richards, S. A., Lounsbury, K. M., Carey, K. L., and Macara, I. G. (1996) A nuclear export signal is essential for the cytosolic localization of the Ran binding protein, RanBP1. J. Cell Biol. 134, 1157-1168 (Pubitemid 26300162)
76. Samuels, A. L., Klinken, S. P., and Ingley, E. (2009) Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin-induced differentiation. Blood 113, 3845-3856
77. Dong, J. M., Lau, L. S., Ng, Y. W., Lim, L., and Manser, E. (2009) Paxillin nuclear-cytoplasmic localization is regulated by phosphorylation of the LD4 motif: Evidence that nuclear paxillin promotes cell proliferation. Biochem. J. 418, 173-184
78. Petit, M. M., Fradelizi, J., Golsteyn, R. M., Ayoubi, T. A., Menichi, B., Louvard, D., Van de Ven, W. J., and Friederich, E. (2000) LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity. Mol. Biol. Cell 11, 117-129 (Pubitemid 30075510)
79. Nix, D. A., Fradelizi, J., Bockholt, S., Menichi, B., Louvard, D., Friederich, E., and Beckerle, M. C. (2001) Targeting of zyxin to sites of actin membrane interaction and to the nucleus. J. Biol. Chem. 276, 34759-34767