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Virologica Sinica

, Volume 25, Issue 2, pp 79–85 | Cite as

The nucleocytoplasmic transport of viral proteins

  • Qiong Ding
  • Lei Zhao
  • Hong Guo
  • Alan C. Zheng
Article

Abstract

Molecules can enter the nucleus by passive diffusion or active transport mechanisms, depending on their size. Small molecules up to size of 50–60 kDa or less than 10 nm in diameter can diffuse passively through the nuclear pore complex (NPC), while most proteins are transported by energy driven transport mechanisms. Active transport of viral proteins is mediated by nuclear localization signals (NLS), which were first identified in Simian Virus 40 large T antigen and had subsequently been identified in a large number of viral proteins. Usually they contain short stretches of lysine or arginine residues. These signals are recognized by the importin super-family (importin α and β) proteins that mediate the transport across the nuclear envelope through Ran-GTP. In contrast, only one class of the leucine-rich nuclear export signal (NES) on viral proteins is known at present. Chromosome region maintenance 1 (CRM1) protein mediates nuclear export of hundreds of viral proteins through the recognition of the leucine-rich NES.

Key words

Nuclear localization signal (NLS) Nuclear export signal (NES) Nuclear pore complex (NPC) Viral proteins 

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References

  1. 1.
    Allen T D, Cronshaw J M, Bagley S, et al. 2000. The nuclear pore complex: mediator of translocation between nucleus and cytoplasm. J Cell Sci, 113(Pt 10): 1651–1659.PubMedGoogle Scholar
  2. 2.
    Bayliss R, Littlewood T, Stewart M. 2000. Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking. Cell, 102: 99–108.CrossRefPubMedGoogle Scholar
  3. 3.
    Boulo S, Akarsu H, Ruigrok R W, et al. 2007. Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes. Virus Res, 124: 12–21.CrossRefPubMedGoogle Scholar
  4. 4.
    Bremner K H, Seymour L W, Pouton C W. 2001. Harnessing nuclear localization pathways for transgene delivery. Curr Opin Mol Ther, 3: 170–177.PubMedGoogle Scholar
  5. 5.
    Chen T, Brownawell A M, Macara I G. 2004. Nucleocytoplasmic shuttling of JAZ, a new cargo protein for exportin-5. Mol Cell Biol, 24: 6608–6619.CrossRefPubMedGoogle Scholar
  6. 6.
    Conti E, Muller C W, Stewart M. 2006. Karyopherin flexibility in nucleocytoplasmic transport. Curr Opin Struct Biol, 16: 237–244.CrossRefPubMedGoogle Scholar
  7. 7.
    Dingwall C, Robbins J, Dilworth S M, et al. 1988. The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen. J Cell Biol, 107: 841–849.CrossRefPubMedGoogle Scholar
  8. 8.
    Dong X, Biswas A, Suel K E, et al. 2009. Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature, 458: 1136–1141.CrossRefPubMedGoogle Scholar
  9. 9.
    Eulalio A, Nunes-Correia I, Carvalho A L, et al. 2004. Two African swine fever virus proteins derived from a common precursor exhibit different nucleocytoplasmic transport activities. J Virol, 78: 9731–9739.CrossRefPubMedGoogle Scholar
  10. 10.
    Fahrenkrog B, Aebi U. 2002. The vertebrate nuclear pore complex: from structure to function. Results Probl Cell Differ, 35: 25–48.PubMedGoogle Scholar
  11. 11.
    Fornerod M, Ohno M, Yoshida M, et al. 1997. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell, 90: 1051–1060.CrossRefPubMedGoogle Scholar
  12. 12.
    Fukuda M, Asano S, Nakamura T, et al. 1997. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature, 390: 308–311.CrossRefPubMedGoogle Scholar
  13. 13.
    Guo H, Ding Q, Lin F, et al. 2009. Characterization of the Nuclear and Nucleolar Localization Signals of Bovine Herpesvirus-1 Infected Cell Protein 27. Virus Res, 145: 312–320.CrossRefPubMedGoogle Scholar
  14. 14.
    Hodel M R, Corbett A H, Hodel A E. 2001. Dissection of a nuclear localization signal. J Biol Chem, 276: 1317–1325.CrossRefPubMedGoogle Scholar
  15. 15.
    Kalab P, Weis K, Heald R. 2002. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science, 295: 2452–2456.CrossRefPubMedGoogle Scholar
  16. 16.
    Kalderon D, Richardson W D, Markham A F, et al. 1984. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature, 311: 33–38.CrossRefPubMedGoogle Scholar
  17. 17.
    Kosugi S, Hasebe M, Matsumura N, et al. 2009. Six classes of nuclear localization signals specific to different binding grooves of importin alpha. J Biol Chem, 284: 478–485.CrossRefPubMedGoogle Scholar
  18. 18.
    Kudo N, Matsumori N, Taoka H, et al. 1999. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci USA, 96: 9112–9117.CrossRefPubMedGoogle Scholar
  19. 19.
    la Cour T, Kiemer L, Molgaard A, et al. 2004. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel, 17: 527–536.CrossRefPubMedGoogle Scholar
  20. 20.
    Lange A, Mills R E, Lange C J, et al. 2007. Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem, 282: 5101–5105.CrossRefPubMedGoogle Scholar
  21. 21.
    Lee B J, Cansizoglu A E, Suel K E, et al. 2006. Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell, 126: 543–558.CrossRefPubMedGoogle Scholar
  22. 22.
    Lee C H, Chang S C, Wu C H, et al. 2001. A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly. J Biol Chem, 276: 8142–8148.CrossRefPubMedGoogle Scholar
  23. 23.
    Lischka P, Rosorius O, Trommer E, et al. 2001. A novel transferable nuclear export signal mediates CRM1-independent nucleocytoplasmic shuttling of the human cytomegalovirus transactivator protein pUL69. EMBO J, 20: 7271–7283.CrossRefPubMedGoogle Scholar
  24. 24.
    Michael W M, Choi M, Dreyfuss G. 1995. A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway. Cell, 83: 415–422.CrossRefPubMedGoogle Scholar
  25. 25.
    Miyamoto Y, Imamoto N, Sekimoto T, et al. 1997. Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors. J Biol Chem, 272: 26375–26381.CrossRefPubMedGoogle Scholar
  26. 26.
    Nair R, Carter P, Rost B. 2003. NLSdb: database of nuclear localization signals. Nucleic Acids Res, 31: 397–399.CrossRefPubMedGoogle Scholar
  27. 27.
    Ossareh-Nazari B, Bachelerie F, Dargemont C. 1997. Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science, 278: 141–144.CrossRefPubMedGoogle Scholar
  28. 28.
    Ossareh-Nazari B, Dargemont C. 1999. Domains of Crm1 involved in the formation of the Crm1, RanGTP, and leucine-rich nuclear export sequences trimeric complex. Exp Cell Res, 252: 236–241.CrossRefPubMedGoogle Scholar
  29. 29.
    Peters R. 2006. Introduction to nucleocytoplasmic transport: molecules and mechanisms. Methods Mol Biol, 322: 235–258.CrossRefPubMedGoogle Scholar
  30. 30.
    Quimby B B, Dasso M. 2003. The small GTPase Ran: interpreting the signs. Curr Opin Cell Biol, 15: 338–344.CrossRefPubMedGoogle Scholar
  31. 31.
    Roberts B L, Richardson W D, Smith A E. 1987. The effect of protein context on nuclear location signal function. Cell, 50: 465–475.CrossRefPubMedGoogle Scholar
  32. 32.
    Rowland R R, Yoo D. 2003. Nucleolar-cytoplasmic shuttling of PRRSV nucleocapsid protein: a simple case of molecular mimicry or the complex regulation by nuclear import, nucleolar localization and nuclear export signal sequences. Virus Res, 95: 23–33.CrossRefPubMedGoogle Scholar
  33. 33.
    Siomi H, Dreyfuss G. 1995. A nuclear localization domain in the hnRNP A1 protein. J Cell Biol, 129: 551–560.CrossRefPubMedGoogle Scholar
  34. 34.
    Smith A E, Slepchenko B M, Schaff J C, et al. 2002. Systems analysis of Ran transport. Science, 295: 488–491.CrossRefPubMedGoogle Scholar
  35. 35.
    Suel K E, Chook Y M. 2009. Kap104p imports the PY-NLS-containing transcription factor Tfg2p into the nucleus. J Biol Chem, 284:15416–15424.CrossRefPubMedGoogle Scholar
  36. 36.
    Zheng C, Brownlie R, Babiuk L A, et al. 2004. Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1. Virology, 324: 327–339.CrossRefPubMedGoogle Scholar
  37. 37.
    Zheng C, Brownlie R, Babiuk L A, et al. 2005. Characterization of the nuclear localization and nuclear export signals of bovine herpesvirus 1 VP22. J Virol, 79: 11864–11872.CrossRefPubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Qiong Ding
    • 1
  • Lei Zhao
    • 1
  • Hong Guo
    • 1
  • Alan C. Zheng
    • 1
  1. 1.State Key Laboratory, Wuhan Institute of VirologyChinese Academy of SciencesWuhanChina

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