Nucleocytoplasmic transport: Signals, mechanisms and regulation

Nature

Volumn 386, Issue 6627, 1997, Pages 779-787

  Nigg, Erich A ^a  

^a UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CELL NUCLEUS; CELL NUCLEUS MEMBRANE; DNA REPLICATION; INTRACELLULAR TRANSPORT; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW; RNA SYNTHESIS; SIGNAL TRANSDUCTION;

EID: 0030964105     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/386779a0     Document Type: Review

References (137)

1. Gerace, L. Nuclear export signals and the fast track to the cytoplasm. Cell 82, 341-344 (1995).
2. Goldberg, M. W. & Allen, T. D. Structural and functional organization of the nuclear envelope. Curr. Opin. Cell Biol. 7, 301-309 (1995).
3. Görlich, D. & Mattaj, I. W. Nucleocytoplasmic transport. Science 271, 1513-1518 (1996).
4. Izaurralde, E. & Mattaj, I. W. RNA export. Cell 81, 153-159 (1995).
5. Panté, N. & Aebi, U. Exploring nuclear pore complex structure and function in molecular detail. J. Cell Sci. (suppl.) 19, 1-11 (1995).
6. Nigg, E. A. Mechanisms of signal transduction to the cell nucleus. Adv. Cancer Res. 55, 271-310 (1990).
7. Karin, M. & Hunter, T. Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus. Curr. Biol. 5, 747-757 (1995).
8. Borer, R. A., Lehner, C. F., Eppenberger, H. M. & Nigg, E. A. Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell 56, 379-390 (1989).
9. Schmidt-Zachmann, M. S., Dargemont, C., Kuhn, L. C. & Nigg, E. A. Nuclear export of proteins: the role of nuclear retention. Cell 74, 493-504 (1993).
10. Pinol-Roma, S. & Dreyfuss, G. Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature 355, 730-732 (1992).
11. Meyer, B. E. & Malim, M. H. The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm. Genes Dev. 8, 1538-1547 (1994).
12. Kalland, K. H., Szilvay, A. M., Brokstad, K. A., Saetrevik, W. & Haukenes, G. The human immunodeficiency virus type 1 Rev protein shuttles between the cytoplasm and nuclear compartments. Mol. Cell. Biol. 14, 7436-7444 (1994).
13. Nakielny, S., Fischer, U., Michael, W. M. & Dreyfuss, G. RNA transport. Annu. Rev. Neurosci. 20, 269-298 (1997).
14. Bukrinsky, M. I. et al. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365, 666-669 (1993).
15. Powers, M. A. & Forbes, D. J. Cytosolic factors in nuclear transport: what's importin? Cell 79, 931-934 (1994).
16. Koepp, D. M. & Silver, P. A. A GTPase controlling nuclear trafficking: running the right way or walking RANdomly? Cell 87, 1-4 (1996).
17. Feldherr, C. M. & Akin, D. EM visualization of nucleocytoplasmic transport processes. Electron Microsc. Rev. 3, 73-86 (1990).
18. Davis, L. I. The nuclear pore complex. Annu. Rev. Biochem. 64, 865-896 (1995).
19. Hinshaw, J. E., Carragher, B. O. & Milligan, R. A. Architecture and design of the nuclear pore complex. Cell 69, 1133-1141 (1992).
20. Akey, C. W. & Radermacher, M. Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy. J. Cell Biol. 122, 1-19 (1993).
21. Bastos, R., Panté, N. & Burke, B. Nuclear pore complex proteins. Int. Rev. Cytol. 162B, 257-302 (1995).
22. Rout, M. P. & Blobel, G. Isolation of the yeast nuclear pore complex. J. Cell Biol. 123, 771-783 (1993).
23. Doye, V. & Hurt, E. C. Genetic approaches to nuclear pore structure and function. Trends. Genet. 11, 235-241 (1995).
24. Radu, A., Moore, M. S. & Blobel, G. The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex. Cell 81, 215-222 (1995).
25. Rexach, M. & Blobel, G. Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell 83, 683-692 (1995).
26. Iovine, M. K., Watkins, J. L. & Wente, S. R. The GLFG repetitive region of the nucleoporin Nup116p interacts with Kap95p, an essential yeast nuclear import factor. J. Cell Biol. 131, 1699-1713 (1995).
27. Stutz, F., Izaurralde, E., Mattaj, I. W. & Rosbash, M. 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, 7144-7150 (1996).
28. Buss, F. & Stewart, M. Macromolecular interactions in the nucleoporin p62 complex of rat nuclear pores: binding of nucleoporin p54 to the rod domain of p62. J. Cell Biol. 128, 251-261 (1995).
29. Grandi, P. et al. A novel nuclear pore protein Nup82p which specifically binds to a fraction of Nsp1p. J. Cell Biol. 130, 1263-1273 (1995).
30. Grandi, P., Schlaich, N., Tekotte, H. & Hurt, E. C. Functional interaction of Nic96p with a core nucleoporin complex consisting of Nsplp, Nup49p and a novel protein Nup57p. EMBO J. 14, 76-87 (1995).
31. Hu, T., Guan, T. & Gerace, L. Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins. J. Cell Biol. 134, 589-601 (1996).
32. Sukegawa, J. & Blobel, G. A nuclear pore complex protein that contains zinc finger motifs, binds DNA, and faces the nucleoplasm. Cell 72, 29-38 (1993).
33. Panté, N., Bastos, R., McMorrow, I., Burke, B. & Aebi, U. Interactions and three-dimensional localization of a group of nuclear pore complex proteins. J. Cell Biol. 126, 603-617 (1994).
34. Wu, J., Matunis, M. J., Kraemer, D., Blobel, G. & Coutavas, E. 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, 14209-14213 (1995).
35. Yokoyama, N. et al. A giant nucleopore protein that binds Ran/TC4. Nature 376, 184-188 (1995).
36. Fabre, E., Boelens, W. C., Wimmer, C., Mattaj, I. W. & Hurt, E. C. Nup145p is required for nuclear export of mRNA and binds homopolymeric RNA in vitro via a novel conserved motif. Cell 78, 275-289 (1994).
37. Kraemer, D., Wozniak, R. W., Blobel, G. & Radu, A. The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm. Proc. Natl Acad. Sci. USA 91, 1519-1523 (1994).
38. Borrow, J. et al. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nature Genet. 12, 159-167 (1996).
39. Byrd, D. A. et al. Tpr, a large coiled coil protein whose amino terminus is involved in activation of oncogenic kinases, is localized to the cytoplasmic surface of the nuclear pore complex. J. Cell Biol. 127, 1515-1526 (1994).
40. Dingwall, C. & Laskey, R. A. Nuclear targeting sequences-a consensus? Trends Biochem. Sci. 16, 478-481 (1991).
41. Makkerh, J. P. S., Dingwall, C. & Laskey, R. A. Comparative mutagenesis of nuclear localization signals reveals the importance of neutral and acidic amino acids. Curr. Biol. 6, 1025-1027 (1996).
42. Breeuwer, M. & Goldfarb, D. S. Facilitated nuclear transport of histone H1 and other small nudeophilic proteins. Cell 60, 999-1008 (1990).
43. Fischer, U., Huber, J., Boelens, W. C., Mattaj, I. W. & Lührmann, R. 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 (1995).
44. Wen, W., Meinkoth, J. L., Tsien, R. Y. & Taylor, S. S. Identification of a signal for rapid export of proteins from the nucleus. Cell 82, 463-473 (1995).
45. Siomi, H. & Dreyfuss, G. A nuclear localization domain in the hnRNP A1 protein. J. Cell Biol. 129, 551-560 (1995).
46. Michael, W. M., Choi, M. & Dreyfuss, G. A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway. Cell 83, 415-422 (1995).
47. Weighardt, F., Biamonti, G. & Riva, S. Nudeo-cytoplasmic distribution of human hnRNP proteins: a search for the targeting domains in hnRNP A1. J. Cell Sci 108, 545-555 (1995).
48. Guddat, U., Bakken, A. H. & Pieler, T. Protein-mediated nuclear export of RNA: 5S rRNA containing small RNPs in Xenopus oocytes. Cell 60, 619-628 (1990).
49. Fridell, R. A. et al. 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, 2936-2940 (1996).
50. Bataillé, N., Helser, T. & Fried, H. M. Cytoplasmic transport of ribosomal subunits microinjected into the Xenopus laevis oocyte nucleus: a generalized, facilitated process. J. Cell Biol. 111, 1571-1582 (1990).
51. Pokrywka, N. J. & Goldfarb, D. S. Nuclear export pathways of tRNA and 40 S ribosomes include both common and specific intermediates. J. Biol. Chem. 270, 3619-3624 (1995).
52. Moore, M. S. & Blobel, G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature 365, 661-663 (1993).
53. Melchior, F., Paschal, B., Evans, J. & Gerace, L. 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 (1993).
54. Weis, K., Dingwall, C. & Lamond, A. I. Characterization of the nuclear protein import mechanism using Ran mutants with altered nucleotide binding specificities. EMBO J. 15, 7120-7128 (1996).
55. Sweet, D. J. & Gerace, L. A GTPase distinct from Ran is involved in nuclear protein import. J. Cell Biol. 133, 971-983 (1996).
56. Coutavas, E., Ren, M., Oppenheim, J. D., D'Eustachio, P. & Rush, M. G. Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4. Nature 366, 585-587 (1993).
57. Bischoff, F. R., Krebber, H., Smirnova, E., Dong, W. & Ponstingl, H. Co-activation of RanGTPase and inhibition of GTP dissociation by Ran-GTP binding protein RanBP1. EMBO J. 14, 705-715 (1995).
58. Melchior, F., Guan, T., Yokoyama, N., Nishimoto, T. & Gerace, L. GTP hydrolysis by Ran occurs at the nuclear pore complex in an early step of protein import. J. Cell Biol. 131, 571-581 (1995).
59. Dingwall, C., Kandels Lewis, S. & Seraphin, B. A family of Ran binding proteins that includes nucleoporins. Proc. Natl Acad. Sci. USA 92, 7525-7529 (1995).
60. Chi, N. C., Adam, E. J. H., Visser, G. D. & Adam, S. A. RanBP1 stabilizes the interaction of Ran with p97 in nuclear protein import. J. Cell Biol. 135, 559-569 (1996).
61. Görlich, D., Panté, N., Kutay, U., Aebi, U. & Bischoff, F. R. Identification of different roles for RanGDP and RanGTP in nuclear protein import. EMBO J. 15, 5584-5594 (1996).
62. Tachibana, T., Imamoto, N., Seino, H., Nishimoto, T. & Yoneda, Y. Loss of RCC1 leads to suppression of nuclear protein import in living cells. J. Biol. Chem. 269, 24542-24545 (1994).
63. Corbett, A. H. et al. Rna1p, a Ran/TC4 GTPase activating protein, is required for nuclear import. J. Cell Biol. 130, 1017-1026 (1995).
64. Amberg, D. C., Fleischmann, M., Stagljar, I., Cole, C. N. & Aebi, M. Nuclear PRP20 protein is required for mRNA export. EMBO J. 12, 233-241 (1993).
65. Kadowaki, T., Goldfarb, D., Spitz, L. M., Tartakoff, A. M. & Ohno, M. Regulation of RNA processing and transport by a nuclear guanine nucleotide release protein and members of the Ras superfamily. EMBO J. 12, 2929-2937 (1993).
66. Schlenstedt, G., Wong, D. H., Koepp, D. M. & Silver, P. A. Mutants in a yeast Ran binding protein are defective in nuclear transport. EMBO J. 14, 5367-5378 (1995).
67. Koepp, D. M., Wong, D. H., Corbett, A. H. & Silver, P. A. Dynamic localization of the nuclear import receptor and its interactions with transport factors. J. Cell Biol. 133, 1163-1176 (1996).
68. Moroianu, J. & Blobel, G. Protein export from the nucleus requires the GTPase Ran and GTP hydrolysis. Proc. Natl Acad. Sci. USA 92, 4318-4322 (1995).
69. Cheng, Y., Dahlberg, J. E. & Lund, E. Diverse effects of the guanine nucleotide exchange factor RCC1 on RNA transport. Science 267, 1807-1810 (1995).
70. Newmeyer, D. D., Finlay, D. R. & Forbes, D. J. In vitro transport of a fluorescent nuclear protein and exclusion of non-nuclear proteins. J. Cell Biol. 103, 2091-2102 (1986).
71. Adam, S. A., Marr, R. S. & Gerace, L. Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors. J. Cell Biol. 111, 807-816 (1990).
72. Görlich, D., Prehn, S., Laskey, R. A. & Hartmann, E. Isolation of a protein that is essential for the first step of nuclear protein import. Cell 79, 767-778 (1994).
73. Görlich, D., Vogel, F., Mills, A. D., Hartmann, E. & Laskey, R. A. Distinct functions for the two importin subunits in nuclear protein import. Nature 377, 246-248 (1995).
74. Radu, A., Blobel, G. & Moore, M. S. Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins. Proc. Natl Acad. Sci. USA 92, 1769-1773 (1995).
75. Imamoto, N. et al. In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting complex in nuclear protein import. EMBO J. 14, 3617-3626 (1995).
76. Imamoto, N., Tachibana, T., Matsubae, M. & Yoneda, Y. A karyophilic protein forms a stable complex with cytoplasmic components prior to nuclear pore binding. J. Biol. Chem. 270, 8559-8565 (1995).
77. Görlich, D. et al. Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope. Curr. Biol. 5, 383-392 (1995).
78. Weis, K., Mattaj, I. W. & Lamond, A. I. Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences. Science 268, 1049-1053 (1995).
79. Chi, N. C., Adam, E. J. & Adam, S. A. Sequence and characterization of cytoplasmic nuclear protein import factor p97. J. Cell Biol. 130, 265-274 (1995).
80. Panté, N. & Aebi, U. Sequential binding of import ligands to distinct nucleopore regions during their nuclear import. Science 273, 1729-1732 (1996).
81. Pollard, V. W. et al. A novel receptor-mediated nuclear protein import pathway. Cell 86, 985-994 (1996).
82. Aitchison, J. D., Blobel, G. & Rout, M. P. Kap104p: a karyopherin involved in the nuclear transport of messenger RNA binding proteins. Science 274, 624-627 (1996).
83. Enenkel, C., Blobel, G. & Rexach, M. Identification of a yeast karyopherin heterodimer that targets import substrate to mammalian nuclear pore complexes. J. Biol. Chem. 270, 16499-16502 (1995).
84. Weis, K., Ryder, U. & Lamond, A. I. The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import. EMBO J. 15, 1818-1825 (1996).
85. Torok, I. et al. The overgrown hematopoietic organs-31 rumor suppressor gene of Drosophila encodes an importin-like protein accumulating in the nucleus at the onset of mitosis. J. Cell Biol. 129, 1473-1489 (1995).
86. Küssel, P. & Frasch, M. Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation. J. Cell Biol. 129, 1491-1507 (1995).
87. Moore, M. S. & Blobel, G. Purification of a Ran-interacting protein that is required for protein import into the nucleus. Proc. Natl Acad. Sci. USA 91, 10212-10216 (1994).
88. Paschal, B. M. & Gerace, L. Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62. J. Cell Biol. 129, 925-937 (1995).
89. Corbett, A. H. & Silver, P. A. The NTF2 gene encodes an essential, highly conserved protein that functions in nuclear transport in vivo. J. Biol. Chem. 271, 18477-18484 (1996).
90. Paschal, B. M., Delphin, C. & Gerace, L. Nucleotide-specific interaction of Ran/TC4 with nuclear transport factors NTF2 and p97. Proc. Natl. Acad. Sci. USA 93, 7679-7683 (1996).
91. Nehrbass, U. & Blobel, G. Role of the nuclear transport factor p10 in nuclear import. Science 272, 120-122 (1996).
92. Lounsbury, K. M., Richards, S. A., Perlungher, R. R. & Macara, I. G. Ran binding domains promote the interaction of Ran with p97/beta-karyopherin, linking the docking and translocation steps of nuclear import. J. Biol. Chem. 271, 2357-2360 (1996).
93. Panté, N. & Aebi, U. Toward the molecular dissection of protein import into nuclei. Curr. Opin. Cell Biol. 8, 397-406 (1996).
94. Simon, S. M., Peskin, C. S. & Oster, G. F. What drives the translocation of proteins? Proc. Natl Acad. Sci. USA 89, 3770-3774 (1992).
95. Moroianu, J., Blobel, G. & Radu, A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabets heterodimer by displacing alpha from an overlapping binding site on beta. Proc. Natl Acad. Sci. USA 93, 7059-7062 (1996).
96. Moroianu, J., Hijikata, M., Blobel, G. & Radu, A. Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins. Proc Natl Acad. Sci. USA 92, 6532-6536 (1995).
97. Azuma, Y., Tabb, M. M., Vu, L. & Nomura, M. Isolation of a yeast protein kinase that is activated by the protein encoded by SRP1 (Srp1p) and phosphorylates Srp1p complexed with nuclear localization signal peptides. Proc. Natl Acad. Sci. USA 92, 5159-5163 (1995).
98. Görlich, D., Henklein, P., Laskey, R. A. & Hartmann, E. A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus. EMBO J. 15, 1810-1817 (1996).
99. Marshallsay, C. & Lührmann, R. In vitro nuclear import of snRNPs: cytosolic factors mediate m3G-cap dependence of U1 and U2 snRNP transport. EMBO J. 13, 222-231 (1994).
100. Michaud, N. & Goldfarb, D. S. Multiple pathways in nuclear transport: the import of U2 snRNP occurs by a novel kinetic pathway. J. Cell Biol. 112, 215-223 (1991).
101. Palacios, I., Weis, K., Klebe, C., Mattaj, I. W. & Dingwall, C. RAN/TC4 mutants identify a common requirement for snRNP and protein import into the nucleus. J. Cell Biol. 133, 485-494 (1996).
102. Dreyfuss, G., Matunis, M. J., Pinol-Roma, S. & Burd, C. G. hnRNP proteins and the biogenesis of mRNA. Annu. Rev. Biochem. 62, 289-321 (1993).
103. Lee, M. S., Henry, M. & Silver, P. A. A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export. Genes Dev. 10, 1233-1246(1996).
104. Mehlin, H., Daneholt, B. & Skoglund, U. Structural interaction between the nuclear pore complex and a specific translocating RNP particle. J. Cll Biol. 129, 1205-1216 (1995).
105. Visa, N., Izaurralde, E., Ferreira, J., Daneholt, B. & Mattaj, I. W. A nuclear cap-binding complex binds Balbiani ring pre-mRNA cotranscriptionally and accompanies the ribonucleoprotein particle during nuclear export. J. Cell Biol. 133, 5-14 (1996).
106. Visa, N. et al. A pre-mRNA-binding protein accompanies the RNA from the gene through the nuclear pores and into polysomes. Cell 84, 253-264 (1996).
107. Zasloff, M. tRNA transport from the nucleus in a eukaryotic cell: carrier-mediated translocation process. Proc. Natl Acad. Sci. USA 80, 6436-6440 (1983).
108. Jarmolowski, A. Boelens, W. C., Izaurralde, E. & Mattaj, I. W. Nuclear export of different classes of RNA is mediated by specific factors. J. Cell Biol. 124, 627-635 (1994).
109. Amberg, D. C., Goldstein, A. L. & Cole, C. N. Isolation and characterization of RAT1: an essential gene of Saccharomyces cerevisiae required for the efficient nucleocytoplasmic trafficking of mRNA. Genes Dev. 6, 1173-1189 (1992).
110. Kadowaki, T. et al. Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants. J. Cell Biol. 126, 649-659 (1994).
111. Fischer, U. et al. Evidence that HIV-1 Rev directly promotes the nuclear export of unspliced RNA. EMBO J. 13, 4105-4112 (1994).
112. Bogerd, H. P., Fridell, R. A., Benson, R. E. & Cullen, B. R. Protein sequence requirements for function of the human T-cell leukemia virus type I Rex nuclear export signal delineated by a novel in vivo randomization-selection assay. Mol. Cell. Biol. 16, 4207-4214 (1996).
113. Fritz, C. C. & Green, M. R. HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs. Curr. Biol. 6, 848-854 (1996).
114. Fridell, R. A., Bogerd, H. P. & Cullen, B. R. Nuclear export of late HIV-1 mRNAs occurs via a cellular protein export pathway. Proc. Natl Acad. Sci. USA 93, 4421-4424 (1996).
115. Fritz, C. C., Zapp, M. L. & Green, M. R. A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature 376, 530-533 (1995).
116. Bogerd, H. P., Fridell, R. A., Madore, S. & Cullen, B. R. Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell 82, 485-494 (1995).
117. Stutz, F., Neville, M. & Rosbash, M. Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell 82, 495-506 (1995).
118. Murphy, R. & Wente, S. R. An RNA-export mediator with an essential nuclear export signal. Nature 383, 357-360 (1996).
119. Singleton, D. R., Chen, S., Hitomi, M., Kumagai, C. & Tartakoff, A. M. A yeast protein that bidirectionally affects nucleocytoplasmic transport. J. Cell Sci. 108, 265-272 (1995).
120. Izaurralde, E., Stepinski, J., Darzynkiewicz, E. & Mattaj, I. W. A cap binding protein that may mediate nuclear export of RNA polymerase II-transcribed RNAs. J. Cell Biol. 118, 1287-1295 (1992).
121. Terns, M. P., Dahlberg, J. E. & Lund, E. Multiple cis-acting signals for export of pre-U1 snRNA from the nucleus. Genes. Dev. 7, 1898-1908 (1993).
122. Izaurralde, E. et al. A cap-binding protein complex mediating U snRNA export. Nature 376, 709-712 (1995).
123. Saavedra, C., Tung, K. S., Amberg, D. C., Hopper, A. K. & Cole, C. N. Regulation of mRNA export in response to stress in Saccharomyces cerevisiae. Genes Dev. 10, 1608-1620 (1996).
124. Görlich, D. et al. Importin provides a link between nuclear protein import and U snRNA export. Cell 87, 21-32 (1996).
125. Feldherr, C. M. & Akin, D. Role of nuclear trafficking in regulating cellular activity. Int. Rev. Cytol. 151, 183-228 (1994).
126. Wang, X., Sato, R., Brown, M. S., Hua, X. & Goldstein, J. L. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77, 53-62 (1994).
127. Moll, T., Tebb, G., Surana, U., Robitsch, H. & Nasmyth, K. The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SW15. Cell 66, 743-758 (1991).
128. Arenzana-Seisdedos, F. et al. Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B. Mol. Cell Biol. 15, 2689-2696 (1995).
129. Guiochon-Mantel, A. et al. Nucleocytoplasmic shuttling of the progesterone receptor. EMBO J. 10, 3851-3859 (1991).
130. Dingwall, C., Sharnick, S. V. & Laskey, R. A. A polypeptide domain that specifies migration of nucleoplasmin into the nucleus. Cell 30, 449-458 (1982).
131. Adam, S. A. & Gerace, L. Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import. Cell 66, 837-847 (1991).
132. Moor, M. S. & Blobel, G. The two steps of nuclear import, targeting to the nuclear envelope and translocation through the nuclear pore, require different cytosolic factors. Cell 69, 939-950 (1992).
133. Scheffzek, K., Klebe, C., Fritz Wolf, K., Kabsch, W. & Wittinghofer, A. Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form. Nature 374, 378-381 (1995).
134. Bullock, T. L., Clarkson, W. D., Kent, H. M. & Stewart, M. The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2). J. Mol. Biol. 260, 422-431 (1996).
135. Baeuerle, P. A. & Henkel, T. Function and activation of NFκB in the immune system. Annu. Rev. Immunol. 12, 540-546 (1994).
136. Jarnik, M. & Aebi, U. Toward a more complete 3-D structure of the nuclear pore complex. J. Struct. Biol. 107, 291-308 (1991).
137. Panté, N. & Aebi, U. Toward the molecular details of the nuclear pore complex. J. Struct. Biol. 113, 179-189 (1994).