Nuclear Protein Import

Distinct Intracellular Receptors for DifferentTypes of Import Substrates
  • David A. Jans
  • Jade K. Forwood
Part of the Molecular Biology Intelligence Unit book series (MBIU)


Entry into the eukaryotic cell nucleus occurs through multiple pathways involving specific targeting signals, and intracellular receptor molecules of the importin/karyopherin superfamily which recognise and dock the nuclear import substrates carrying these signals at the nuclear pore. Subsequent to translocation through the pore via a series of importin-mediated docking steps at multiple sites within it, release into the nucleus is effected by the monomeric guanine nucleotide binding protein Ran. Different importins possess distinct target sequence-binding specificities, meaning that different importins mediate the nuclear import of different classes of proteins. This extends to different classes of transcription factors which are recognised by distinct importins, and whose transport to the nucleus is modulated by specific regulatory mechanisms. The first step of nuclear import is of central importance, with the affinity of the importin: targeting signal interaction being a critical parameter in determining transport efficiency. In the whole cell context, target signal recognition can be modulated through differential expression of the importins themselves, as well as through competition between different importins for the same nuclear import substrate, and between different nuclear import substrates for the same importin. In addition, there are specific mechanisms to modulate targeting sequence-importin interaction directly through phosphorylation. The fact that there are distinct nuclear import pathways for different types of nuclear import substrates enables the cell to regulate these pathways specifically, ensuring efficient nuclear import of particular proteins as and when required.


Nuclear Localization Signal Nuclear Import Nuclear Pore Complex Nuclear Transport Importin Beta 
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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  1. 1.
    Wozniak RW, Rout WP, Aitchison JD. Karyopherins and kissing cousins. Trends Cell Biol 1998; 8:184–188.PubMedCrossRefGoogle Scholar
  2. 2.
    Jans DA, Xiao C-Y, Lam MHC. Nuclear targeting signal recognition: A key control point in nuclear transport? BioEssays 2000; 22:532–544.PubMedCrossRefGoogle Scholar
  3. 3.
    Hood JK, Silver PA. In or out? Regulating nuclear transport. Curr Opin Cell Biol 1999; 11:241–247.PubMedCrossRefGoogle Scholar
  4. 4.
    Gorlich D, Kutay U. Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol 1999; 15:607–660.PubMedCrossRefGoogle Scholar
  5. 5.
    Ribbeck K, Lipowsky G, Kent HM et al. NTF2 mediates nuclear import of Ran. EMBO J 1998; 17:6587–6598.PubMedCrossRefGoogle Scholar
  6. 6.
    Bischoff FR, Ponstingl H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature 1991; 354:80–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Jans DA, Chan CK, Hübner S. Signals mediating nuclear targeting and their regulation: Application in drug delivery. Med Res Rev 1998; 18:189–223.PubMedCrossRefGoogle Scholar
  8. 8.
    Melchior F, Gerace L. Two-way trafficking with Ran. Trends Cell Biol 1998; 8:175–179.PubMedCrossRefGoogle Scholar
  9. 9.
    Doye V, Hurt E. From nucleoporins to nuclear pore complexes. Current Opin Cell Biol 1997; 9:401–411.CrossRefGoogle Scholar
  10. 10.
    Rexach M, Blobel G. Protein import into nuclei: Association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell 1995; 83:683–692.PubMedCrossRefGoogle Scholar
  11. 11.
    Bayliss R, Littlewood T, Stewart, M. Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking. Cell 2000; 102:99–108.PubMedCrossRefGoogle Scholar
  12. 12.
    Stewart M. Insights into the molecular mechanism of nuclear trafficking using nuclear transport factor 2 (NTF2). Cell Struct Funct 2000; 25:217–225.PubMedCrossRefGoogle Scholar
  13. 13.
    Izaurralde E, Kutay U, von Kobbe C et al. The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. EMBO J 1997; 16:6535–6547.PubMedCrossRefGoogle Scholar
  14. 14.
    Engelmeier L, Olivio J-C, Mattaj IW. Receptor-mediated substrate translocation through the nuclear pore complex without nucleotide triphosphate hydrolysis. Current Biol 1999; 9:30–41.CrossRefGoogle Scholar
  15. 15.
    Efthymiadis A, Shao H, Hübner S et al. Kinetic characterization of the human retinoblastoma protein bipartite nuclear localization sequence in vivo and in vitro: A comparison with the SV40 large T-antigen NLS. J Biol Chem 1997; 272:22134–22139.PubMedCrossRefGoogle Scholar
  16. 16.
    Kutay U, Bischoff FR, Kostka S et al. Export of importin α from the nucleus is mediated by a specific nuclear transport factor. Cell 1997; 90:1061–1071.PubMedCrossRefGoogle Scholar
  17. 17.
    Kalderon D, Roberts BL, Richardson WD et al. A short amino acid sequence able to specify nuclear location. Cell 1984; 39:499–509.PubMedCrossRefGoogle Scholar
  18. 18.
    Robbins J, Dilworth SM, Laskey RA et al. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: Identification of a class of bipartite nuclear targeting sequence. Cell 1991; 64:615–623.PubMedCrossRefGoogle Scholar
  19. 19.
    Hall NM, Craik C, Hiraoka Y. Homeodomain of yeast repressor alpha 2 contains a nuclear localization signal. Proc Natl Acad Sci USA 1990; 87:6954–6958.PubMedCrossRefGoogle Scholar
  20. 20.
    Makkerh JS, Dingwall C, Laskey RA. Comparative mutagenesis of nuclear localization signals reveals the importance of neutral and acidic amino acids. Current Biol 1996; 6:1025–1027.CrossRefGoogle Scholar
  21. 21.
    Smith HM, Hicks GR, Raikhel NV. Importin alpha from Arabidopsis thaliana is a nuclear import receptor that recognizes three classes of import signals. Plant Physiol 1997; 114:411–417.PubMedCrossRefGoogle Scholar
  22. 22.
    Briggs LJ, Stein D, Goltz J et al. The cAMP-dependent protein kinase site (Ser312) enhances dorsal nuclear import through facilitating nuclear localization sequence/importin interaction. J Biol Chem 1998; 273:22745–22752.PubMedCrossRefGoogle Scholar
  23. 23.
    Hu W, Jans DA. Efficiency of importin (α/βmediated NLS recognition and nuclear import: Differential role of NTF2. J Biol Chem 1999; 274:15820–15827.PubMedCrossRefGoogle Scholar
  24. 24.
    Hübner S, Smith HMS, Hu W et al. Plant importin α binds nuclear localization sequences with high affinity and mediates nuclear import independent of importin β. J Biol Chem 1999; 274:22610–22617.PubMedCrossRefGoogle Scholar
  25. 25.
    Hübner S, Xiao C-Y, Jans DA. The protein kinase CK2 site (Ser111/112) enhances recognition of the SV40 large T-antigen nuclear localization sequence by importin. J Biol Chem 1997; 272:17191–17195.PubMedCrossRefGoogle Scholar
  26. 26.
    Kohler M, Speck C, Christiansen M et al. Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import. Mol Cell Biol 1999; 19:7782–91.PubMedGoogle Scholar
  27. 27.
    Seki T, Tada S, Katada T et al. Cloning of a cDNA encoding a novel importin-α homologue, Qip1: discrimination of Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase Q1/RecQL. Biochem Biophys Res Commun 1997; 234:48–53.PubMedCrossRefGoogle Scholar
  28. 28.
    Nadler SG, Tritschler D, Haffar OK et al. Differential expression and sequence-specific interaction of karyopherin α with nuclear localization sequences. J Biol Chem 1997; 272:4310–4315.PubMedCrossRefGoogle Scholar
  29. 29.
    Miyamoto Y, Imamoto N, Sekimoto T et al. Differential modes of nuclear localization signal (NLS) recognition by three different classes of NLS receptors. J Biol Chem 1997; 272:26375–26381.PubMedCrossRefGoogle Scholar
  30. 30.
    Herold A, Truant R, Wiegand H et al. Determination of the functional domain organization of the importin α nuclear import factor. J Cell Biol 1998; 143:309–318.PubMedCrossRefGoogle Scholar
  31. 31.
    Cuomo CA, Kirch SA, Gyuris J et al. Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein. Proc Natl Acad Sci USA 1994; 91:6156–6160.PubMedCrossRefGoogle Scholar
  32. 32.
    Prieve MG, Guttridge KL, Munguia J et al. The nuclear localization signal of lymphoid enhancer factor-1 is reconized by two differentially expressed Srp1-nuclear localization sequence receptor proteins. J Biol Chem 1996; 271:7654–7658PubMedCrossRefGoogle Scholar
  33. 33.
    Prieve MG, Guttridge KL, Munguia J et al. Differential importin-α recognition and nuclear trans port by nuclear localization signals within the high-mobility-group DNA binding domains of lymphoid enhancer Factor 1 and T-cell factor 1. Mol Cell Biol 1998; 18:4819–4832.PubMedGoogle Scholar
  34. 34.
    Fischer N, Kremmer E, Lautscham G et al. Epstein-Barr virus nuclear antigen 1 forms a complex with the nuclear transporter karyopherin α2. J Biol Chem 1997; 272:3888–4005.Google Scholar
  35. 35.
    Gallay P, Hope T, Chin D et al. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci USA 1997; 94:9825–9830.PubMedCrossRefGoogle Scholar
  36. 36.
    Gallay P, Stitt V, Mundy C et al. Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J Virol 1996; 70:1027–1032.PubMedGoogle Scholar
  37. 37.
    Gascard P, Nunomura W, Lee G et al. Deciphering the nuclear import pathway for the cytoskeletal red cell protein 4.1R. Mol Biol Cell 1999; 10:1783–1798.PubMedGoogle Scholar
  38. 38.
    Nakai A, Ishikawa T. Nuclear localisation signal is essential for stress-induced dimer-to trimer transition of heat shock transcription factor 3. J Biol Chem 2000; 275:34665–34671.PubMedCrossRefGoogle Scholar
  39. 39.
    Johnson-Saliba M, Siddon NA, Clarkson MJ et al. Distinct importin recognition properties of histones and chromatin assembly factors. FEBS Lett 2000; 467:169–174PubMedCrossRefGoogle Scholar
  40. 40.
    Peng X, Zhang Y, Zhang H et al. Interaction of tissue transglutaminase with nuclear transport protein importin-α3. FEBS Lett 1999; 446:35–39.PubMedCrossRefGoogle Scholar
  41. 41.
    Nachury MV, Ryder UW, Lamond AI et al. Cloning and characterization of hSRPl gamma, a tissue-specific nuclear transport factor. Proc Natl Acad Sci USA 1998; 95:582–587.PubMedCrossRefGoogle Scholar
  42. 42.
    Li S, Ku C-Y, Farmer AA et al. Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs. J Biol Chem 1998; 273:6183–6189.PubMedCrossRefGoogle Scholar
  43. 43.
    Cortes P, Ye ZS et al. RAG-1 interacts with the repeated amino acid motif of the human homo-logue of the yeast protein SRP1. Proc Natl Acad Sci USA 1994; 91:7633–7637.PubMedCrossRefGoogle Scholar
  44. 44.
    Sekimoto T, Imamoto N, Nakajima K et al. Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1. EMBO J 1997; 16:7067–7077.PubMedCrossRefGoogle Scholar
  45. 45.
    Chen C-F, Li S, Chen Y et al. The nuclear localization sequences of the BRCA1 protein interact with the importin-α subunit of the nuclear transport signal receptor. J Biol Chem 1996; 271:32863–32868.PubMedCrossRefGoogle Scholar
  46. 46.
    Huber J, Cronshagen U, Kadokura M et al. Snurportin 1, an m3G-cap-specific nuclear import receptor with a novel domain structure. EMBO J 1998; 17:4114–4126.PubMedCrossRefGoogle Scholar
  47. 47.
    Jullien D, Görlich D, Laemmli UK et al. Nuclear import of RPA in Xenopus egg extracts requires a novel protein XRIPα but not importin a. EMBO J 1999; 18:4348–4358.PubMedCrossRefGoogle Scholar
  48. 48.
    Tiganis T, Flint AJ, Adam AS et al. Association of the T-cell protein tyrosine phosphatase with nuclear import factor p97. J Biol Chem 1997; 272:21548–21557.PubMedCrossRefGoogle Scholar
  49. 49.
    Moore JD, Yang J, Truant R et al. Nuclear import of cdk/cydin complexes: identification of distinct mechanisms for import of cdk2/cyclin E and cdc2/cydin B1. J Cell Biol 1999; 144:213–224.PubMedCrossRefGoogle Scholar
  50. 50.
    Jaekel S, Görlich D. Importin β, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. EMBO J 1998; 17:4491–4502.CrossRefGoogle Scholar
  51. 51.
    Truant R, Cullen BR. The arginine-rich domains present in human immunodeficiency virus type 1 Tat and Rev function as direct importin β-dependent nuclear localization signals. Mol Cell Biol 1999; 19:1210–1217.PubMedGoogle Scholar
  52. 52.
    Henderson, BR, Percipalle G. 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 1997; 274:693–707.PubMedCrossRefGoogle Scholar
  53. 53.
    Palmeri D, Malim MH. Importin β can mediate the nuclear import of an arginine-rich nuclear localization signal in the absence of importin α. Mol Cell Biol 1999; 19:1218–1225.PubMedGoogle Scholar
  54. 54.
    Xiao Z, Liu X, Lodish HF. Importin beta mediates nuclear translocation of Smad 3. J Biol Chem 2000; 275:23425–23428.PubMedCrossRefGoogle Scholar
  55. 55.
    Nagoshi E, Imamoto N, Sato R et al. Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip. Mol Biol Cell 1999; 10:2221–2233.PubMedGoogle Scholar
  56. 56.
    Nagoshi E, Yoneda Y. Dimerization of sterol regulatory element-binding protein 2 via the helix-loop-helix-leucine zipper domain is a prerequisite for its nuclear localization mediated by importin beta. Mol Cell Biol 2001; 21:2779–2789.PubMedCrossRefGoogle Scholar
  57. 57.
    Lam MHC, Hu W, Xiao CY et al. Molecular dissection of the Importin βl-recognized nuclear targeting signal of parathyroid hormone-related protein. Biochem Biophys Res Commun 2001; 282:629–634.PubMedCrossRefGoogle Scholar
  58. 58.
    Lam MHC, Briggs LJ, Hu W et al. Importin β recognizes parathyroid hormone-related protein (PTHrP) with high affinity and mediates its nuclear import in the absence of importin α. J Biol Chem 1999; 274:7391–7398.PubMedCrossRefGoogle Scholar
  59. 59.
    Chan CK, Hübner S, Hu W et al. Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: Implications for nonviral DNA delivery. Gene Therapy 1998; 5:1204–1212.PubMedCrossRefGoogle Scholar
  60. 60.
    Forwood JK, Lam MHC, Jans DA. Nuclear import of the CREB and AP-1 transcription factors is dependent on importin β1 and Ran, and independent of importin α. Biochemistry 2001; 40: 5208–5217.PubMedGoogle Scholar
  61. 61.
    Preiss S, Argentaro A, Clayton A et al. Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding and transcriptional activation. J Biol Chem 2001; 276:27864–27872.PubMedCrossRefGoogle Scholar
  62. 62.
    Forwood JK, Harley V, Jans DA. The C-terminal nuclear localization signal of the SRY HMG-domain mediates nuclear import through importin β1. J Biol Chem 2001; 276:46575–46582.PubMedCrossRefGoogle Scholar
  63. 63.
    Forwood JK, unpublished observations.Google Scholar
  64. 64.
    Schedlich LA, Le Page SL, Firth SM et al. Nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) and IGFBP-5 is mediated by the importin β subunit. J Biol Chem 2001; 275:23462–23470.CrossRefGoogle Scholar
  65. 65.
    Pollard VW, Michael WM, Nakielny S et al. A novel receptor-mediated nuclear protein import pathway. Cell 1996; 86:985–994.PubMedCrossRefGoogle Scholar
  66. 66.
    Bogerd HP, Benson RE, Truant R et al. Definition of a consensus transportin-specific nucleocyto-plasmic transport signal. J Biol Chem 1999; 274:9771–9777.PubMedCrossRefGoogle Scholar
  67. 67.
    Siomi H, Eder PS, Kataoka N et al. Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins. J Cell Biol 1997; 138:1181–1192.PubMedCrossRefGoogle Scholar
  68. 68.
    Nakielny S, Shaikh S, Burke B et al. Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain. EMBO J 1999; 18:1982–1995.PubMedCrossRefGoogle Scholar
  69. 69.
    Siomi MC, Fromont M, Rain J-C et al. Functional conservation of the transportin nuclear import pathway in divergent organisms. Mol Cell Biol 1998; 18:4141–4148.PubMedGoogle Scholar
  70. 70.
    Schlenstedt G, Smirnova E, Deane R et al. Yrb4p, a yeast Ran-GTP-binding protein involved in import of ribosomal protein L25 into the nucleus. EMBO J 1997; 16:6237–6249.PubMedCrossRefGoogle Scholar
  71. 71.
    Kaffman A, Rank NM, O’Shea EK. Phosphorylation regulates association of the transcription factor Pho4 with its import receptor Psel/Kap121. Genes Dev 1998; 12:2673–2683.PubMedGoogle Scholar
  72. 72.
    Komeili A, O’Shea EK. Roles of phosphorylation sites in regulating activity of the transcription factor Pho4. Science 1999; 284:977–980.PubMedCrossRefGoogle Scholar
  73. 73.
    Pemberton LF, Rosenblum JS, Blobel G. Nuclear import of the TATA-binding protein: mediation by the karyopherin Kap114p and a possible mechanism for intranuclear targeting. J Cell Biol 1999; 145:1407–1417.PubMedCrossRefGoogle Scholar
  74. 74.
    Delahodde A, Pandjaitan R, Corral-Debrinski M et al. Pse/Kap 121-dependent nuclear localisation of the major yeast mulitdrug (MDR) transcription factor Pdr1. Mol Microbiol 2001; 39:304–312.PubMedCrossRefGoogle Scholar
  75. 75.
    Albertini M, Pemberton LF, Rosenblum JS et al. A novel nuclear import pathway for the transcription factor TFIIS. J Cell Biol 1998; 143:1447–1455.PubMedCrossRefGoogle Scholar
  76. 76.
    Ferrigno P, Posas F, Koepp D et al. Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin β homologs NMD5 and XPO1. EMBO J 1998; 17:5606–5614.PubMedCrossRefGoogle Scholar
  77. 77.
    Titov AA, Blobel G. The karyopherin Kap122p/Pdr6p imports both subunits of the transcription factor IIA into the nucleus. J Cell Biol 1999; 147:235–245.PubMedCrossRefGoogle Scholar
  78. 78.
    Rosenblum JS, Pemberton LF, Blobel G. A nuclear import pathway for a protein involved in tRNA maturation. J Cell Biol 1997; 139:1655–1661.PubMedCrossRefGoogle Scholar
  79. 79.
    Senger B, Simos G, Bischoff FR et al. Mtr10p functions as a nuclear import receptor for the mRNA-binding protein Np13p. EMBO J 1998; 17:2196–2207.PubMedCrossRefGoogle Scholar
  80. 80.
    Kataoka N, Bachorik JL, Dreyfuss D. Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol 1999; 145:1145–1152.PubMedCrossRefGoogle Scholar
  81. 81.
    Jaekel S, Albig W, Kutay U et al. The importin β/importin 7 heterodimer is a functional nuclear import receptor for histone Hl. EMBO J 1999; 18:2411–2423.CrossRefGoogle Scholar
  82. 82.
    Kudo N, Khochbin S, Nishi K et al. Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins. J Biol Chem 1997; 272:29742–29751.PubMedCrossRefGoogle Scholar
  83. 83.
    Shiozaki K, Yanagida M. Functional dissection of the phosphorylated termini of fission yeast DNA topoisomerase II. J Cell Biol 1992; 119:1023–1036.PubMedCrossRefGoogle Scholar
  84. 84.
    Jans DA, Moll T, Nasmyth K et al. Cyclin-dependent kinase site-regulated signal-dependent nuclear localization of the SW15 yeast transcription factor in mammalian cells. J Biol Chem 1995; 270:17064–17067.PubMedCrossRefGoogle Scholar
  85. 85.
    Conti E, Uy M, Leighton L et al. Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin a. Cell 1998; 94:193–204.PubMedCrossRefGoogle Scholar
  86. 86.
    Conti E, Kuriyan J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure Fold Des 2000; 8:329–338.PubMedCrossRefGoogle Scholar
  87. 87.
    Fontes MR, Teh T, Kobe B. Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha. J Mol Biol 2000; 297:1183–1194.PubMedCrossRefGoogle Scholar
  88. 88.
    Kobe, B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin a. Nature Struct Biol 1999; 6:388–397.PubMedCrossRefGoogle Scholar
  89. 89.
    Tsuji L, Takumi T, Imamoto N et al. Identification of novel homologues of mouse importin a, the a subunit of the nuclear pore-targeting complex, and their tissue-specific expression. FEBS Lett 1997; 416;30–34.PubMedCrossRefGoogle Scholar
  90. 90.
    Torok I, Strand D, Schmitt R et al. The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an Importin-like protein accumulating in the nucleus at the onset of mitosis. J Cell Biol 1995; 129:1473–1489.PubMedCrossRefGoogle Scholar
  91. 91.
    Mathe E, Bates H, Huikeshoven H et al. Importin-alpha3 is required at multiple stages of Drosophila development and has a role in the completion of oogenesis. Dev Biol 2000; 223:307–322.PubMedCrossRefGoogle Scholar
  92. 92.
    Geles KG, Adam SA. Germline and developmental roles of the nuclear transport factor importin (X3 in C. elegans. Development 2001; 128:1817–1830.PubMedGoogle Scholar
  93. 93.
    Cingolani G, Petosa C, Weis K et al. Structure of importin-β bound to the IBB domain of importin α. Nature 1999; 399:221–229.PubMedCrossRefGoogle Scholar
  94. 94.
    Chook YM, Blobel G. Structure of the nuclear transport complex karyopherin-β-2-Ran. GppNHp. Nature 1999; 399:230–237.PubMedCrossRefGoogle Scholar
  95. 95.
    Chi NC, Adam EJH, Adam SA. Different binding domains for Ran-GTP and Ran-GDP/RanBP1 on nuclear import factor p97. J Biol Chem 1997; 272:6818–6822.PubMedCrossRefGoogle Scholar
  96. 96.
    Lee SJ, Imamoto N, Sakai H et al. The adoption of a twisted structure of importin-beta is essential for the protein-protein interaction required for nuclear transport. J Mol Biol 2000; 302:251–264.PubMedCrossRefGoogle Scholar
  97. 97.
    Görlich D, Dabrowski M, Bischoff FR et al. A novel class of RanGTP binding proteins. J Cell Biol 1997; 138:65–80.PubMedCrossRefGoogle Scholar
  98. 98.
    Tirian L, Puro J, Erdelyi M et al. The KetelD dominant-negative mutations identify maternal function of the Drosophila importin-β gene required for cleavage nuclear formation. Gentics 2000; 156:1901–1912.Google Scholar
  99. 99.
    Lippai M, Tirian L, Boros I et al. The Ketel gene encodes a Drosophila homologue of importin-β. Genetics 2000; 156:1889–1900.PubMedGoogle Scholar
  100. 100.
    Xiao C-Y, Hübner S, Jans DA. SV40 large tumor-antigen nuclear import is regulated by the double-stranded DNA-dependent protein kinase site (serine 120) flanking to the nuclear localization seuence. J Biol Chem 1997; 272:22191–22198.PubMedCrossRefGoogle Scholar
  101. 101.
    Xiao C-Y, Jans P, Jans DA. Negative charge at the protein kinase CK2 site enhances recognition of the SV40 large tumor-antigen nuclear localization signal by importin; Effect of proline near the CK2 site. FEBS Lett 1998; 440:297–301.PubMedCrossRefGoogle Scholar
  102. 102.
    Huxford T, Huang D-B, Malek S et al. The crystal structure of the IkBα/NF-κB complex reveals mechanisms of NF-κB inactivation. Cell 1999; 95:759–770.CrossRefGoogle Scholar
  103. 103.
    Henkel T, Zabel U, Van Zee K et al. Intramolecular masking of the nuclear localization signal and dimerization domain in the precursor for the p50 NF-κB subunit. Cell 1992; 68:1121–1133.PubMedCrossRefGoogle Scholar
  104. 104.
    Strehlow I, Schindler C. Amino-terminal signal transducer and activator of transcription (STAT) domains regulate nuclear translocation and STAT deactivation. J Biol Chem 1998; 273:28049–28056.PubMedCrossRefGoogle Scholar
  105. 105.
    Lacasse EC, Lefebvre YA. Nuclear localization signals overlap DNA-or RNA-binding domains in nucleic acid-binding proteins. Nucleic Acids Res 1995; 23:1647–1656.PubMedCrossRefGoogle Scholar
  106. 106.
    Grasser KD, Feix G. Isolation and characterization of maize cDNAs encoding a high mobility group protein displaying a HMG-box. Nucleic Acids Res 1991; 19:2573–2577.PubMedCrossRefGoogle Scholar
  107. 107.
    Kubitscheck U, Wedekind P, Zeidler O et al. Single nuclear pores visualized by confocal micros-copy and image processing. Biophys J 1996; 70:2067–2077.PubMedCrossRefGoogle Scholar
  108. 108.
    Keminer O, Siebrasse JP, Zerf K et al. Optical recording of signal-mediated protein transport through single nuclear pore complexes. Proc Natl Acad Sci USA 1999; 96:11842–11847.PubMedCrossRefGoogle Scholar
  109. 109.
    Kruhlak MJ, Lever MA, Fischle W et al. Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state speckle compartments. J Cell Biol 2000; 150:41–51.PubMedCrossRefGoogle Scholar
  110. 110.
    McNally JG, Muller WG, Walker D et al. The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 2000; 287:1262–1265.PubMedCrossRefGoogle Scholar
  111. 111.
    Lam MH, Thomas RJ, Loveland KL et al. Nuclear transport of parathyroid hormone (PTH)-related protein is dependent on microtubules. Mol Endocrinol 2002; 16(2):390–401.PubMedCrossRefGoogle Scholar

Copyright information

© and Kluwer Academic / Plenum Publishers 2005

Authors and Affiliations

  • David A. Jans
    • 1
  • Jade K. Forwood
    • 2
  1. 1.Department for Biochemistry and Molecular BiologyMonash UniversityClaytonAustralia
  2. 2.Nuclear Signaling Laboratory Department of Biochemistry and Molecular BiologyMonash UniversityClaytonAustralia

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