Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2003 Sep 1;374(Pt 2):545–550. doi: 10.1042/BJ20021890

Characterization of the bipartite nuclear localization signal of protein LANA2 from Kaposi's sarcoma-associated herpesvirus.

Cesar Muñoz-Fontela 1, Estefanía Rodríguez 1, Cesar Nombela 1, Javier Arroyo 1, Carmen Rivas 1
PMCID: PMC1223601  PMID: 12767255

Abstract

LANA2 is a nuclear latent protein detected exclusively in Kaposi's sarcoma-associated herpesvirus-infected B cells. The protein inhibits p53-dependent transactivation and apoptosis, suggesting an important role in the transforming activity of the virus. To explore the molecular mechanisms of its nuclear localization, fusion proteins of green fluorescent protein (EGFP) and deletion constructs of LANA2 were expressed in HeLa cells. Only the fragment comprising amino acid residues 355-440 of LANA2 localized in the cell nucleus. This fragment contains two closely located basic domains and forms a putative bipartite nuclear localization signal (NLS). The putative LANA2 NLS was able to target EGFP to the nucleus consistently. Site-directed mutation analyses demonstrated that LANA2 contains a functional bipartite NLS between amino acid positions 367 and 384. In addition, analysis of cells transfected with a cytoplasmic LANA2 mutant revealed that an appropriate subcellular localization may be crucial to regulate p53 activity.

Full Text

The Full Text of this article is available as a PDF (149.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adam S. A. Transport pathways of macromolecules between the nucleus and the cytoplasm. Curr Opin Cell Biol. 1999 Jun;11(3):402–406. doi: 10.1016/S0955-0674(99)80056-8. [DOI] [PubMed] [Google Scholar]
  2. Bayliss R., Corbett A. H., Stewart M. The molecular mechanism of transport of macromolecules through nuclear pore complexes. Traffic. 2000 Jun;1(6):448–456. doi: 10.1034/j.1600-0854.2000.010602.x. [DOI] [PubMed] [Google Scholar]
  3. Boulikas T. Nuclear localization signals (NLS). Crit Rev Eukaryot Gene Expr. 1993;3(3):193–227. [PubMed] [Google Scholar]
  4. Cesarman E., Knowles D. M. The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. Semin Cancer Biol. 1999 Jun;9(3):165–174. doi: 10.1006/scbi.1998.0118. [DOI] [PubMed] [Google Scholar]
  5. Corbett A. H., Silver P. A. Nucleocytoplasmic transport of macromolecules. Microbiol Mol Biol Rev. 1997 Jun;61(2):193–211. doi: 10.1128/mmbr.61.2.193-211.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dingwall C., Laskey R. A. Nuclear targeting sequences--a consensus? Trends Biochem Sci. 1991 Dec;16(12):478–481. doi: 10.1016/0968-0004(91)90184-w. [DOI] [PubMed] [Google Scholar]
  7. Ganem D. KSHV and Kaposi's sarcoma: the end of the beginning? Cell. 1997 Oct 17;91(2):157–160. doi: 10.1016/s0092-8674(00)80398-0. [DOI] [PubMed] [Google Scholar]
  8. Görlich D., Kutay U. Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol. 1999;15:607–660. doi: 10.1146/annurev.cellbio.15.1.607. [DOI] [PubMed] [Google Scholar]
  9. Lubyova B., Pitha P. M. Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors. J Virol. 2000 Sep;74(17):8194–8201. doi: 10.1128/jvi.74.17.8194-8201.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miller M., Park M. K., Hanover J. A. Nuclear pore complex: structure, function, and regulation. Physiol Rev. 1991 Jul;71(3):909–949. doi: 10.1152/physrev.1991.71.3.909. [DOI] [PubMed] [Google Scholar]
  11. Moore P. S., Boshoff C., Weiss R. A., Chang Y. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science. 1996 Dec 6;274(5293):1739–1744. doi: 10.1126/science.274.5293.1739. [DOI] [PubMed] [Google Scholar]
  12. Moore P. S., Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med. 1995 May 4;332(18):1181–1185. doi: 10.1056/NEJM199505043321801. [DOI] [PubMed] [Google Scholar]
  13. Nakielny S., Dreyfuss G. Transport of proteins and RNAs in and out of the nucleus. Cell. 1999 Dec 23;99(7):677–690. doi: 10.1016/s0092-8674(00)81666-9. [DOI] [PubMed] [Google Scholar]
  14. Pemberton L. F., Blobel G., Rosenblum J. S. Transport routes through the nuclear pore complex. Curr Opin Cell Biol. 1998 Jun;10(3):392–399. doi: 10.1016/s0955-0674(98)80016-1. [DOI] [PubMed] [Google Scholar]
  15. Rivas C., Thlick A. E., Parravicini C., Moore P. S., Chang Y. Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J Virol. 2001 Jan;75(1):429–438. doi: 10.1128/JVI.75.1.429-438.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Soulier J., Grollet L., Oksenhendler E., Cacoub P., Cazals-Hatem D., Babinet P., d'Agay M. F., Clauvel J. P., Raphael M., Degos L. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood. 1995 Aug 15;86(4):1276–1280. [PubMed] [Google Scholar]
  17. Stauber R., Gaitanaris G. A., Pavlakis G. N. Analysis of trafficking of Rev and transdominant Rev proteins in living cells using green fluorescent protein fusions: transdominant Rev blocks the export of Rev from the nucleus to the cytoplasm. Virology. 1995 Nov 10;213(2):439–449. doi: 10.1006/viro.1995.0016. [DOI] [PubMed] [Google Scholar]
  18. Stoffler D., Fahrenkrog B., Aebi U. The nuclear pore complex: from molecular architecture to functional dynamics. Curr Opin Cell Biol. 1999 Jun;11(3):391–401. doi: 10.1016/S0955-0674(99)80055-6. [DOI] [PubMed] [Google Scholar]
  19. Vasu S. K., Forbes D. J. Nuclear pores and nuclear assembly. Curr Opin Cell Biol. 2001 Jun;13(3):363–375. doi: 10.1016/s0955-0674(00)00221-0. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES