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Exportin-Mediated Nuclear Export of Proteins and Ribonucleoproteins

  • Maarten Fornerod
  • Mutsuhito Ohno
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 35)

Abstract

Protein export from the nucleus of eukaryotic cells serves three main purposes: (1) to remove factors that are only transiently required in the nucleus — transcriptional signaling molecules fall into this category; (2) to participate in RNA export — all RNAs that leave the nucleus, do so in complex with proteins; (3) to recycle import factors that have been dissociated from their cargoes and have to return to the cytoplasm for a further round. A fourth conceivable function is to remove proteins that have unintentionally entered the nucleus, e.g. by diffusion or by inclusion into a reforming nucleus after mitosis.

Keywords

Human Immunodeficiency Virus Type Nuclear Export Feline Immunodeficiency Virus Nuclear Pore Complex Nuclear Export Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adachi Y, Yanagida M (1989) Higher order chromosome structure is affected by cold-sensitive mutations in a Schizosaccharomyces pombe gene crml+ which encodes a 115-kD protein preferentially localized in the nucleus and its periphery. J Cell Biol 108: 1195–1207PubMedCrossRefGoogle Scholar
  2. Alepuz PM, Matheos D, Cunningham KW, Estruch F (1999) The Saccharomyces cerevisiae RanGTP-binding protein msn5p is involved in different signal transduction pathways. Genetics 153: 1219–1231PubMedGoogle Scholar
  3. Arts GJ, Fornerod M, Mattaj IW (1998) Identification of a nuclear export receptor for tRNA. Curr Biol 8: 305–314PubMedCrossRefGoogle Scholar
  4. Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J (1998) The specificity of the CRM1Rev nuclear export signal interaction is mediated by RanGTP. J Biol Chem 273: 33414–33422PubMedCrossRefGoogle Scholar
  5. Askjaer P, Bachi A, Wilm M, Bischoff FR, Weeks DL, Ogniewski V, Ohno M, Niehrs C, Kjems J, Mattaj IW, Fornerod M (1999) RanGTP-regulated interactions of CRM1 with nucleoporins and a shuttling DEAD-box helicase. Mol Cell Biol 19: 6276–6285PubMedGoogle Scholar
  6. Belgareh N, Snay-Hodge C, Pasteau F, Dagher S, Cole CN, Doye V (1998) Functional characterization of a Nup159p-containing nuclear pore subcomplex. Mol Biol Cell 9: 3475–3492PubMedGoogle Scholar
  7. Bevec D, Jaksche H, Oft M, Wohl T, Himmelspach M, Pacher A, Schebesta M, Koettnitz K, Dobrovnik M, Csonga R, Lottspeich F, Hauber J (1996) Inhibition of HIV-1 replication in lymphocytes by mutants of the Rev cofactor eIF-5 A. Science 271: 1858–1860Google Scholar
  8. Bischoff FR, Görlich D (1997) RanBP1 is crucial for the release of RanGTP from importin beta-related nuclear transport factors. FEBS Lett 419: 249–254PubMedCrossRefGoogle Scholar
  9. Blondel M, Alepuz PM, Huang LS, Shaham S, Ammerer G, Peter M (1999) Nuclear export of Farlp in response to pheromones requires the export receptor Msnsp/Ste21p. Genes Dev 13: 2284–2300PubMedCrossRefGoogle Scholar
  10. Boche I, Fanning E (1997) Nucleocytoplasmic recycling of the nuclear localization signal receptor alpha subunit in vivo is dependent on a nuclear export signal, energy, and RCC1. J Cell Biol 139: 313–325PubMedCrossRefGoogle Scholar
  11. Bogerd HP, Fridell RA, Benson RE, Hua J, Cullen BR (1996) 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 16: 4207–4214PubMedGoogle Scholar
  12. Callanan M, Kudo N, Gout S, Brocard M, Yoshida M, Dimitrov S, Khochbin S (2000) Developmentally regulated activity of CRM1/XPO1 during early Xenopus embryogenesis. J Cell Sci 113: 451–459PubMedGoogle Scholar
  13. Damelin M, Silver PA (2000) Mapping interactions between nuclear transport factors in living cells reveals pathways through the nuclear pore complex. Mol Cell 5: 133–140PubMedCrossRefGoogle Scholar
  14. Dobbelstein M, Roth J, Kimberly WT, Levine AJ, Shenk T (1997) Nuclear export of the E1B 55kDa and E4 34-kDa adenoviral oncoproteins mediated by a rev-like signal sequence. EMBO J 16: 4276–4284PubMedCrossRefGoogle Scholar
  15. Dupont S, Sharova N, DeHoratius C, Virbasius CM, Zhu X, Bukrinskaya AG, Stevenson M, Green MR (1999) A novel nuclear export activity in HIV-1 matrix protein required for viral replication. Nature 402: 681–685PubMedCrossRefGoogle Scholar
  16. Engel K, Kotlyarov A, Gaestel M (1998) Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation. EMBO J 17: 3363–3371PubMedCrossRefGoogle Scholar
  17. Englmeier L, Olivo JC, Mattaj IW (1999) Receptor-mediated substrate translocation through the nuclear pore complex without nucleotide triphosphate hydrolysis. Curr Biol 9: 30–41PubMedCrossRefGoogle Scholar
  18. Farjot G, Sergeant A, Mikaelian I (1999) A new nucleoporin-like protein interacts with both HIV-1 Rev nuclear export signal and CRM-1. J Biol Chem 274: 17309–17317Google Scholar
  19. Feng W, Benko AL, Lee JH, Stanford DR, Hopper AK (1999) Antagonistic effects of NES and NLS motifs determine S. cerevisiae Rnalp subcellular distribution. J Cell Sci 112: 339–347PubMedGoogle Scholar
  20. Fischer U, Huber J, Boelens WC, Mattaj IW, Lührmann 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: 475–483PubMedCrossRefGoogle Scholar
  21. Floer M, Blobel G (1996) The nuclear transport factor karyopherin beta binds stoichiometrically to Ran-GTP and inhibits the Ran GTPase activating protein. J Biol Chem 271: 5313–5316PubMedCrossRefGoogle Scholar
  22. Floer M, Blobel G (1999) Putative reaction intermediates in Crml-mediated nuclear protein export. J Bio! Chem 274: 16279–16286CrossRefGoogle Scholar
  23. Floer M, Blobel G, Rexach M (1997) Disassembly of RanGTP-karyopherin beta complex, an intermediate in nuclear protein import. J Biol Chem 272: 19538–19546PubMedCrossRefGoogle Scholar
  24. Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997a) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90: 1051–1060PubMedCrossRefGoogle Scholar
  25. Fornerod M, van Deursen J, van Baal S, Reynolds A, Davis D, Murti KG, Fransen J, Grosveld G (1997b) The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. EMBO J 16: 807–816PubMedCrossRefGoogle Scholar
  26. Fridell RA, Partin KM, Carpenter S, Cullen BR (1993) Identification of the activation domain of equine infectious anemia virus rev. J Virol 67: 7317–7323PubMedGoogle Scholar
  27. Fridell RA, Fischer U, Liihrmann R, Meyer BE, Meinkoth JL, Malim MH, Cullen BR (1996) Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev. Proc Natl Acad Sci USA 93: 2936–2940CrossRefGoogle Scholar
  28. Fritz CC, Green MR (1996) HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs. Curr Bio! 6: 848–854CrossRefGoogle Scholar
  29. Fukuda M, Gotoh I, Gotoh Y, Nishida E (1996) Cytoplasmic localization of mitogen-activated protein kinase kinase directed by its NH2-terminal, leucine-rich short amino acid sequence, which acts as a nuclear export signal. J Biol Chem 271: 20024–20028PubMedCrossRefGoogle Scholar
  30. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, Nishida E (1997) CRMI is responsible for intracellular transport mediated by the nuclear export signal. Nature 390: 308–311PubMedCrossRefGoogle Scholar
  31. Görlich D, Dabrowski M, Bischoff FR, Kutay U, Bork P, Hartmann E, Prehn S, Izaurralde E (1997) A novel class of RanGTP binding proteins. J Cell Biol 138: 65–80PubMedCrossRefGoogle Scholar
  32. Guan T, Kehlenbach RH, Scirmer EC, Kehlenbach A, Fan F, Clurman BE, Arnheim N, Gerace L (2000) Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear export. Mol Cell Biol 20: 5619–5630PubMedCrossRefGoogle Scholar
  33. Guddat U, Bakken AH, Pieler T (1990) Protein-mediated nuclear export of RNA: 5S rRNA containing small RNPs in Xenopus oocytes. Cell 60: 619–628PubMedCrossRefGoogle Scholar
  34. Hamamoto T, Gunji S, Tsuji H, Beppu T (1983a) Leptomycins A and B, new antifungal antibiotics. I. Taxonomy of the producing strain and their fermentation, purification and characterization. J Antibiot (Tokyo) 36: 639–645CrossRefGoogle Scholar
  35. Hamamoto T, Seto H, Beppu T (1983b) Leptomycins A and B, new antifungal antibiotics. II. Structure elucidation. J Antibiot (Tokyo) 36: 646–650CrossRefGoogle Scholar
  36. Hamm J, Fornerod M (2000) Anti-idiotype RNAs that mimic the leucine-rich nuclear export signal and specifically bind to CRM1/exportin 1. Chem Biol 7: 345–354PubMedCrossRefGoogle Scholar
  37. Hamm J, Mattaj IW (1990) Monomethylated cap structures facilitate RNA export from the nucleus. Cell 63: 109–118PubMedCrossRefGoogle Scholar
  38. Hamm J, Huber J, Lührmann R (1997) Anti-idiotype RNA selected with an anti-nuclear export signal antibody is actively transported in oocytes and inhibits Rev-and cap-dependent RNA export. Proc Natl Acad Sci USA 94: 12839–12844PubMedCrossRefGoogle Scholar
  39. Harris ME, Gontarek RR, Derse D, Hope TJ (1998) Differential requirements for alternative splicing and nuclear export functions of equine infectious anemia virus Rev protein. Mol Cell Biol 18: 3889–3899Google Scholar
  40. Hellmuth K, Lau DM, Bischoff FR, Kunzler M, Hurt E, Simos G (1998) Yeast loslp has properties of an exportin-like nucleocytoplasmic transport factor for tRNA. Mol Cell Biol 18: 6374–6386PubMedGoogle Scholar
  41. Henderson BR, Eleftheriou A (2000) A comparison of the activity, sequence specificity, and CRM1-dependence of different nuclear export signals. Exp Cell Res 256: 213–224PubMedCrossRefGoogle Scholar
  42. Henderson BR, Percipalle P (1997) Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localisation signal mediates specific binding to human importin-beta. J Mol Biol 274: 693–707Google Scholar
  43. Hillig RC, Renault L, Vetter IR, Drell Tt, Wittinghofer A, Becker J (1999) The crystal structure of rnalp: a new fold for a GTPase-activating protein. Mol Cell 3: 781–791PubMedCrossRefGoogle Scholar
  44. Hodge CA, Colot HV, Stafford P, Cole CN (1999) Rat8p/Dbpsp is a shuttling transport factor that interacts with Rat7p/Nup159p and Glelp and suppresses the mRNA export defect of xpol-1 cells. EMBO J 18: 5778–5788PubMedCrossRefGoogle Scholar
  45. Holaska JM, Paschal BM (1998) A cytosolic activity distinct from crml mediates nuclear export of protein kinase inhibitor in permeabilized cells. Proc Natl Acad Sci USA 95: 14739–14744PubMedCrossRefGoogle Scholar
  46. Huang TT, Kudo N, Yoshida M, Miyamoto S (2000) A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NFkappaB/IkappaBalpha complexes. Proc Natl Acad Sci USA 97: 1014–1019PubMedCrossRefGoogle Scholar
  47. Huber J, Cronshagen U, Kadokura M, Marshallsay C, Wada T, Sekine M, Lührmann R (1998) Snurportinl, an m3G-cap-specific nuclear import receptor with a novel domain structure. EMBO J 17: 4114–4126PubMedCrossRefGoogle Scholar
  48. Hurwitz ME, Strambio-de-Castillia C, Blobel G (1998) Two yeast nuclear pore complex proteins involved in mRNA export form a cytoplasmically oriented subcomplex. Proc Natl Acad Sci USA 95: 11241–11245PubMedCrossRefGoogle Scholar
  49. Iovine MK, Wente SR (1997) A nuclear export signal in Kap95p is required for both recycling the import factor and interaction with the nucleoporin GLFG repeat regions of Nup116p and Nup100p. J Cell Biol 137: 797–811PubMedCrossRefGoogle Scholar
  50. Izaurralde E, Lewis J, McGuigan C, Jankowska M, Darzynkiewicz E, Mattaj IW (1994) A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78: 657–668PubMedCrossRefGoogle Scholar
  51. Izaurralde E, Lewis J, Gamberi C, Jarmolowski A, McGuigan C, Mattaj IW (1995) A cap-binding protein complex mediating U snRNA export. Nature 376: 709–712PubMedCrossRefGoogle Scholar
  52. Izaurralde E, Kutay U, von Kobbe C, Mattaj IW, Görlich D (1997) The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. EMBO J 16: 6535–6547PubMedCrossRefGoogle Scholar
  53. Jarmolowski A, Boelens WC, Izaurralde E, Mattaj IW (1994) Nuclear export of different classes of RNA is mediated by specific factors. J Cell Biol 124: 627–635PubMedCrossRefGoogle Scholar
  54. Johnson C, Van Antwerp D, Hope TJ (1999) An N-terminal nuclear export signal is required for the nucleocytoplasmic shuttling of IkappaBalpha. EMBO J 18: 6682–6693PubMedCrossRefGoogle Scholar
  55. Jones AL, Quimby BB, Hood JK, Ferrigno P, Keshava PH, Silver PA, Corbett AH (2000) SAC3 may link nuclear protein export to cell cycle progression. Proc Natl Acad Sci USA 97: 3224–3229PubMedCrossRefGoogle Scholar
  56. Kaffman A, Rank NM, O’Neill EM, Huang LS, O’Shea EK (1998a) The receptor Msn5 exports the phosphorylated transcription factor Pho4 out of the nucleus. Nature 396: 482–486PubMedCrossRefGoogle Scholar
  57. Kaffman A, Rank NM, O’Shea EK (1998b) Phosphorylation regulates association of the transcription factor Pho4 with its import receptor Psel/Kap121. Genes Dev 12: 2673–2683PubMedCrossRefGoogle Scholar
  58. Kataoka N, Ohno M, Moda I, Shimura Y (1995) Identification of the factors that interact with NCBP, an 80kDa nuclear cap binding protein. Nucleic Acids Res 23: 3638–3641PubMedCrossRefGoogle Scholar
  59. Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, 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: 645–657PubMedCrossRefGoogle Scholar
  60. Kim FJ, Beeche AA, Hunter JJ, Chin DJ, Hope TJ (1996) Characterization of the nuclear export signal of human T-cell lymphotropic virus type 1 Rex reveals that nuclear export is mediated by position-variable hydrophobic interactions. Mol Cell Biol 16: 5147–5155PubMedGoogle Scholar
  61. Klemm JD, Beals CR, Crabtree GR (1997) Rapid targeting of nuclear proteins to the cytoplasm. Curr Biol 7: 638–644PubMedCrossRefGoogle Scholar
  62. Kudo N, Wolff B, Sekimoto T, Schreiner EP, Yoneda Y, Yanagida M, Horinouchi S, Yoshida M (1998) Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1. Exp Cell Res 242: 540–547PubMedCrossRefGoogle Scholar
  63. Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner EP, Wolff B, Yoshida M, Horinouchi S (1999a) Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci USA 96: 9112–9117PubMedCrossRefGoogle Scholar
  64. Kudo N, Taoka H, Toda T, Yoshida M, Horinouchi S (1999b) A novel nuclear export signal sensitive to oxidative stress in the fission yeast transcription factor Papl. J Biol Chem 274: 15151–15158PubMedCrossRefGoogle Scholar
  65. Kuge S, Toda T, Iizuka N, Nomoto A (1998) Crml (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress. Genes Cells 3:521–532 Kunzler M, Hurt EC (1998) Cselp functions as the nuclear export receptor for importin alpha in yeast. FEBS Lett 433: 185–190CrossRefGoogle Scholar
  66. Kunzler M, Gerstberger T, Stutz F, Bischoff FR, Hurt E (2000) Yeast ran-binding protein 1 (Yrbl) shuttles between the nucleus and cytoplasm and is exported from the nucleus via a CRM1 (XPO1)-dependent pathway. Mol Cell Biol 20: 4295–4308PubMedCrossRefGoogle Scholar
  67. Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D (1997a) Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. Cell 90: 1061–1071PubMedCrossRefGoogle Scholar
  68. Kutay U, Izaurralde E, Bischoff FR, Mattaj IW, Görlich D (1997b) Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex. EMBO J 16: 1153–1163PubMedCrossRefGoogle Scholar
  69. Kutay U, Lipowsky G, Izaurralde E, Bischoff FR, Schwarzmaier P, Hartmann E, Görlich D (1998) Identification of a tRNA-specific nuclear export receptor. Mol Cell 1: 359–369PubMedCrossRefGoogle Scholar
  70. Li J, Meyer AN, Donoghue DJ (1997) Nuclear localization of cyclin B1 mediates its biological activity and is regulated by phosphorylation. Proc Natl Acad Sci USA 94: 502–507PubMedCrossRefGoogle Scholar
  71. Li Y, Yamakita Y, Krug RM (1998) Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci USA 95: 4864–4869PubMedCrossRefGoogle Scholar
  72. Lipowsky G, Bischoff RF, Schwartzmaier P, Kraft R, Kostka S, Hartmann E, Kutay U, Görlich D (2000) Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes. EMBO J (in press)Google Scholar
  73. Liihrmann R, Kastner B, Bach M (1990) Structure of spliceosomal snRNPs and their role in premRNA splicing. Biochim Biophys Acta 1087: 265–292CrossRefGoogle Scholar
  74. Mahajan R, Delphin C, Guan T, Gerace L, Melchior F (1997) A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88: 97–107PubMedCrossRefGoogle Scholar
  75. Mairy M, Denis H (1972) Biochemical studies on oogenesis. 2. Ribosome assembly during the development of oocytes in Xenopus laevis. Eur J Biochem 25: 535–543PubMedCrossRefGoogle Scholar
  76. Mancuso VA, Hope TJ, Zhu L, Derse D, Phillips T, Parslow TG (1994) Posttranscriptional effector domains in the Rev proteins of feline immunodeficiency virus and equine infectious anemia virus. J Virol 68: 1998–2001Google Scholar
  77. Mattaj IW (1986) Cap trimethylation of U snRNA is cytoplasmic and dependent on U snRNP protein binding. Cell 46: 905–911PubMedCrossRefGoogle Scholar
  78. Matunis MJ, Wu J, Blobel G (1998) SUMO-1 modification and its role in targeting the Ran GTPaseactivating protein, RanGAP1, to the nuclear pore complex. J Cell Biol 140: 499–509PubMedCrossRefGoogle Scholar
  79. Meyer BE, Malim MH (1994) The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm. Genes Dev 8: 1538–1547Google Scholar
  80. Meyer BE, Meinkoth JL, Malim MH (1996) Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: identification of a family of transferable nuclear export signals. J Virol 70: 2350–2359Google Scholar
  81. Mueller L, Cordes VC, Bischoff FR, Ponstingl H (1998) Human RanBP3, a group of nuclear RanGTP binding proteins. FEBS Lett 427: 330–336PubMedCrossRefGoogle Scholar
  82. Murphy R, Wente SR (1996) An RNA-export mediator with an essential nuclear export signal. Nature 383: 357–360PubMedCrossRefGoogle Scholar
  83. Nachury MV, Weis K (1999) The direction of transport through the nuclear pore can be inverted. Proc Natl Acad Sci USA 96: 9622–9627PubMedCrossRefGoogle Scholar
  84. Nakielny S, Shaikh S, Burke B, Dreyfuss G (1999) Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain. EMBO J 18: 1982–1995PubMedCrossRefGoogle Scholar
  85. Neville M, Rosbash M (1999) The NES-Crmlp export pathway is not a major mRNA export route in Saccharomyces cerevisiae. EMBO J 18: 3746–3756PubMedCrossRefGoogle Scholar
  86. Neville M, Stutz F, Lee L, Davis LI, Rosbash M (1997) The importin-beta family member Crmlp bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol 7: 767–775Google Scholar
  87. Nishi K, Yoshida M, Fujiwara D, Nishikawa M, Horinouchi S, Beppu T (1994) Leptomycin B targets a regulatory cascade of crml, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression. J Biol Chem 269: 6320–6324PubMedGoogle Scholar
  88. Noguchi E, Hayashi N, Nakashima N, Nishimoto T (1997) Yrb2p, a Nup2p-related yeast protein, has a functional overlap with Rnalp, a yeast Ran-GTPase-activating protein. Mol Cell Biol 17: 2235–2246PubMedGoogle Scholar
  89. Noguchi E, Saitoh Y, Sazer S, Nishimoto T (1999) Disruption of the YRB2 gene retards nuclear protein export, causing a profound mitotic delay, and can be rescued by overexpression of XPO1/CRM1. J Biochem (Tokyo) 125: 574–585CrossRefGoogle Scholar
  90. Ohno M, Segref A, Bachi A, Wilm M, Mattaj IW (2000) PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation. Cell 101: 187–198PubMedCrossRefGoogle Scholar
  91. Ohshima T, Nakajima T, Oishi T, Imamoto N, Yoneda Y, Fukamizu A, Yagami K (1999) CRM 1 mediates nuclear export of nonstructural protein 2 from parvovirus minute virus of mice. Biochem Biophys Res Commun 264: 144–150PubMedCrossRefGoogle Scholar
  92. O’Neill EM, Kaffman A, Jolly ER, O’Shea EK (1996) Regulation of PHO4 nuclear localization by the PHO80–PHO85 cyclin-CDK complex. Science 271: 209–212PubMedCrossRefGoogle Scholar
  93. Ossareh-Nazari B, Dargemont C (1999) Domains of Crml involved in the formation of the Crml, RanGTP, and leucine-rich nuclear export sequences trimeric complex. Exp Cell Res 252: 236–241Google Scholar
  94. Ossareh-Nazari B, Bachelerie F, Dargemont C (1997) Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science 278: 141–144PubMedCrossRefGoogle Scholar
  95. Otero GC, Harris ME, Donello JE, Hope TJ (1998) Leptomycin B inhibits equine infectious anemia virus Rev and feline immunodeficiency virus rev function but not the function of the hepatitis B virus posttranscriptional regulatory element. J Virol 72: 7593–7597PubMedGoogle Scholar
  96. Palacios I, Hetzer M, Adam SA, Mattaj IW (1997) Nuclear import of U snRNPs requires importin beta. EMBO J 16: 6783–6792PubMedCrossRefGoogle Scholar
  97. Palmeri D, Malim MH (1996) The human T-cell leukemia virus type 1 posttranscriptional trans-activator Rex contains a nuclear export signal. J Virol 70: 6442–6445PubMedGoogle Scholar
  98. Paraskeva E, Izaurralde E, Bischoff FR, Huber J, Kutay U, Hartmann E, Lührmann R, Görlich D (1999) CRM1-mediated recycling of snurportin 1 to the cytoplasm. J Cell Biol 145: 255–264PubMedCrossRefGoogle Scholar
  99. Pasquinelli AE, Powers MA, Lund E, Forbes D, Dahlberg JE (1997) Inhibition of mRNA export in vertebrate cells by nuclear export signal conjugates. Proc Natl Acad Sci USA 94: 14394–14399PubMedCrossRefGoogle Scholar
  100. Plafker K, Macara IG (2000) Facilitated nucleo cytoplasmic shuttling of the Ran binding protein RanBP1. Mol Cell Biol 20: 3510–3521PubMedCrossRefGoogle Scholar
  101. Ribbeck K, Kutay U, Paraskeva E, Görlich D (1999) The translocation of transportin-cargo complexes through nuclear pores is independent of both Ran and energy. Curr Biol 9: 47–50PubMedCrossRefGoogle Scholar
  102. Richards SA, Lounsbury KM, Carey KL, Macara IG (1996) A nuclear export signal is essential for the cytosolic localization of the Ran binding protein, RanBP1. J Cell Biol 134: 1157–1168PubMedCrossRefGoogle Scholar
  103. Richards SA, Carey KL, Macara IG (1997) Requirement of guanosine triphosphate-bound ran for signal-mediated nuclear protein export. Science 276: 1842–1844PubMedCrossRefGoogle Scholar
  104. Rittinger K, Budman J, Xu J, Volinia S, Cantley LC, Smerdon SJ, Gamblin SI, Yaffe MB (1999) Structural analysis of 14–3–3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14–3–3 in ligand binding. Mol Cell 4: 153 – 166PubMedCrossRefGoogle Scholar
  105. Rosorius O, Reichart B, Kratzer F, Heger P, Dabauvalle MC, Hauber J (1999) Nuclear pore localization and nucleocytoplasmic transport of eIF-5A: evidence for direct interaction with the export receptor CRM1. J Cell Sci 112: 2369–2380PubMedGoogle Scholar
  106. Roth J, Dobbelstein M, Freedman DA, Shenk T, Levine AJ (1998) Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein. EMBO J 17: 554–564PubMedCrossRefGoogle Scholar
  107. Ruhl M, Himmelspach M, Bahr GM, Hammerschmid F, Jaksche H, Wolff B, Aschauer H, Farrington GK, Probst H, Bevec D, et al. (1993) Eukaryotic initiation factor 5 A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation. J Cell Biol 123: 1309–1320Google Scholar
  108. Saitoh H, Sparrow DB, Shiomi T, Pu RT, Nishimoto T, Mohun TJ, Dasso M (1998) Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2. Curr Biol 8: 121–124PubMedCrossRefGoogle Scholar
  109. Sandri-Goldin RM (1998) ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes Dev 12: 868–879PubMedCrossRefGoogle Scholar
  110. Shah S, Tugendreich S, Forbes D (1998) Major binding sites for the nuclear import receptor are the internal nucleoporin Nup153 and the adjacent nuclear filament protein Tpr. J Cell Biol 141: 31–49PubMedCrossRefGoogle Scholar
  111. Smitherman M, Lee K, Swanger J, Kapur R, Clurman BE (2000) Characterization and targeted disruption of murine Nup50, a p27-Kip1 interacting component of the nuclear pore complex. Mol Cell Biol 20: 5631–5642PubMedCrossRefGoogle Scholar
  112. Solsbacher J, Maurer P, Bischoff FR, Schlenstedt G (1998) Cselp is involved in export of yeast importin alpha from the nucleus. Mol Cell Biol 18: 6805–6815PubMedGoogle Scholar
  113. Stade K, Ford CS, Guthrie C, Weis K (1997) Exportin 1 ( Crmlp) is an essential nuclear export factor. Celi 90: 1041–1050Google Scholar
  114. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J 18: 1660–1672PubMedCrossRefGoogle Scholar
  115. Stutz F, Izaurralde E, Mattaj IW, Rosbash M (1996) A role for nucleoporin FG repeat domains in export of human immunodeficiency virus type 1 Rev protein and RNA from the nucleus. Mol Cell Biol 16: 7144–7150Google Scholar
  116. Taagepera S, McDonald D, Loeb JE, Whitaker LL, McElroy AK, Wang JY, Hope TJ (1998) Nuclearcytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci USA 95: 7457–7462PubMedCrossRefGoogle Scholar
  117. Taura T, Schlenstedt G, Silver PA (1997) Yrb2p is a nuclear protein that interacts with Prp20p, a yeast Rccl homologue. J Biol Chem 272: 31877–31884PubMedCrossRefGoogle Scholar
  118. Taura T, Krebber H, Silver PA (1998) A member of the Ran-binding protein family, Yrb2p, is involved in nuclear protein export. Proc Natl Acad Sci USA 95: 7427–7432PubMedCrossRefGoogle Scholar
  119. Toone WM, Kuge S, Samuels M, Morgan BA, Toda T, Jones N (1998) Regulation of the fission yeast transcription factor Papl by oxidative stress: requirement for the nuclear export factor Crml ( Exportin) and the stress-activated MAP kinase Styl/Spcl. Genes Dev 12: 1453–1463PubMedCrossRefGoogle Scholar
  120. Toyoshima F, Moriguchi T, Wada A, Fukuda M, Nishida E (1998) Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G2 checkpoint. EMBO J 17: 2728–2735PubMedCrossRefGoogle Scholar
  121. Traglia HM, O’Connor JP, Tung KS, Dallabrida S, Shen WC, Hopper AK (1996) Nucleus-associated pools of Rnalp, the Saccharomyces cerevisiae Ran/TC4 GTPse activating protein involved in nucleus/cytosol transit. Proc Natl Acad Sci USA 93: 7667–7672PubMedCrossRefGoogle Scholar
  122. Vetter IR, Arndt A, Kutay U, Görlich D,Wittinghofer A (1999) Structural view of the Ran-Importin beta interaction at 2.3 A resolution. Cell 97: 635–646Google Scholar
  123. Wada A, Fukuda M, Mishima M, Nishida E (1998) Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein. EMBO J 17: 1635–1641PubMedCrossRefGoogle Scholar
  124. Watanabe M, Fukuda M, Yoshida M,Yanagida M, Nishida E (1999) Involvement of CRM 1, a nuclear export receptor, in mRNA export in mammalian cells and fission yeast. Genes Cells 4: 291–297Google Scholar
  125. Wen W, Meinkoth JL, Tsien RY, Taylor SS (1995) Identification of a signal for rapid export of proteins from the nucleus. Cell 82: 463–473PubMedCrossRefGoogle Scholar
  126. Wolff B, Sanglier JJ, 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: 139–147Google Scholar
  127. Wu J, Matunis MJ, Kraemer D, Blobel G, Coutavas E (1995) Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran- GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region. J Biol Chem 270: 14209–14213PubMedCrossRefGoogle Scholar
  128. Yan C, Lee LH, Davis LI (1998) Crmlp mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO J 17: 7416–7429PubMedCrossRefGoogle Scholar
  129. Yang J, Bardes ES, Moore JD, Brennan J, Powers MA, Kornbluth S (1998) Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Genes Dev 12: 2131–2143PubMedCrossRefGoogle Scholar
  130. Yokoyama N, Hayashi N, Seki T, Panté N, Ohba T, Nishii K, Kuma K, Hayashida T, Miyata T, Aebi U, et al. (1995) A giant nucleopore protein that binds Ran/TC4. Nature 376: 184–188PubMedCrossRefGoogle Scholar
  131. Zhang MJ, Dayton AI (1998) Tolerance of diverse amino acid substitutions at conserved positions in the nuclear export signal (NES) of HIV-1 Rev. Biochem Biophys Res Commun 243: 113–116CrossRefGoogle Scholar
  132. Zolotukhin AS, Felber BK (1997) Mutations in the nuclear export signal of human ran-binding protein RanBP1 block the Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1. J Biol Chem 272: 11356–11360PubMedCrossRefGoogle Scholar
  133. Zolotukhin AS, Felber BK (1999) Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev. J Virol 73: 120–127Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Maarten Fornerod
    • 1
  • Mutsuhito Ohno
    • 1
  1. 1.EMBL Gene Expression ProgrammeHeidelbergGermany

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