Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 May 15;89(10):4290–4294. doi: 10.1073/pnas.89.10.4290

Nuclear translocation of viral Jun but not of cellular Jun is cell cycle dependent.

K Chida 1, P K Vogt 1
PMCID: PMC49067  PMID: 1584763

Abstract

The Jun protein is a transcription factor of the AP-1 complex, and it is concentrated in the cell nucleus. While the cellular Jun protein is transported into the nucleus in a cell-cycle-independent fashion, the oncogenic viral version of the protein translocates into the nucleus most rapidly during the G2 phase of the cell cycle and only slowly during G1 and S phases. This cell cycle dependence of nuclear transport has been mapped to the cysteine to serine mutation in the carboxyl-terminal portion of viral Jun. We have identified a complex nuclear translocation signal located in the basic region of viral Jun. This signal has the sequence ASKSRKRKL. A peptide of this sequence synthesized in vitro and conjugated to IgG can mediate cell-cycle-dependent translocation of the microinjected conjugate from the cytoplasm into the nucleus. The nuclear translocation signal has two functional domains. The pentapeptide RKRKL is sufficient as a cell-cycle-independent nuclear address. The entire signal is needed for cell-cycle-dependent nuclear translocation. The amino-terminal tetrapeptide contains the cysteine to serine substitution responsible for cell cycle dependence. Deletion analysis of the Jun protein suggests that the nuclear translocation signal identified in the basic region is required for nuclear translocation of Jun and may be the only such signal in the Jun molecule.

Full text

PDF
4290

Images in this article

4291Image
on p.4291
4292Image
on p.4292
4292Image
on p.4292
4293Image
on p.4293

Selected References

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

  1. Abate C., Patel L., Rauscher F. J., 3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990 Sep 7;249(4973):1157–1161. doi: 10.1126/science.2118682. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
  3. Ball A. R., Jr, Bos T. J., Löliger C., Nagata L. P., Nishimura T., Su H., Tsuchie H., Vogt P. K. Jun: oncogene and transcriptional regulator. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):687–693. doi: 10.1101/sqb.1988.053.01.078. [DOI] [PubMed] [Google Scholar]
  4. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  5. Bos T. J., Monteclaro F. S., Mitsunobu F., Ball A. R., Jr, Chang C. H., Nishimura T., Vogt P. K. Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences. Genes Dev. 1990 Oct;4(10):1677–1687. doi: 10.1101/gad.4.10.1677. [DOI] [PubMed] [Google Scholar]
  6. Bos T. J., Rauscher F. J., 3rd, Curran T., Vogt P. K. The carboxy terminus of the viral Jun oncoprotein is required for complex formation with the cellular Fos protein. Oncogene. 1989 Feb;4(2):123–126. [PubMed] [Google Scholar]
  7. Garcia-Bustos J., Heitman J., Hall M. N. Nuclear protein localization. Biochim Biophys Acta. 1991 Mar 7;1071(1):83–101. doi: 10.1016/0304-4157(91)90013-m. [DOI] [PubMed] [Google Scholar]
  8. Ghosh S., Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 1990 Apr 12;344(6267):678–682. doi: 10.1038/344678a0. [DOI] [PubMed] [Google Scholar]
  9. Hughes S. H., Greenhouse J. J., Petropoulos C. J., Sutrave P. Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol. 1987 Oct;61(10):3004–3012. doi: 10.1128/jvi.61.10.3004-3012.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Håvarstein L. S., Morgan I. M., Wong W. Y., Vogt P. K. Mutations in the Jun delta region suggest an inverse correlation between transformation and transcriptional activation. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):618–622. doi: 10.1073/pnas.89.2.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kawai S., Nishizawa M. New procedure for DNA transfection with polycation and dimethyl sulfoxide. Mol Cell Biol. 1984 Jun;4(6):1172–1174. doi: 10.1128/mcb.4.6.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Lanford R. E., Kanda P., Kennedy R. C. Induction of nuclear transport with a synthetic peptide homologous to the SV40 T antigen transport signal. Cell. 1986 Aug 15;46(4):575–582. doi: 10.1016/0092-8674(86)90883-4. [DOI] [PubMed] [Google Scholar]
  14. 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 SWI5. Cell. 1991 Aug 23;66(4):743–758. doi: 10.1016/0092-8674(91)90118-i. [DOI] [PubMed] [Google Scholar]
  15. Nasmyth K., Adolf G., Lydall D., Seddon A. The identification of a second cell cycle control on the HO promoter in yeast: cell cycle regulation of SW15 nuclear entry. Cell. 1990 Aug 24;62(4):631–647. doi: 10.1016/0092-8674(90)90110-z. [DOI] [PubMed] [Google Scholar]
  16. Nigg E. A., Baeuerle P. A., Lührmann R. Nuclear import-export: in search of signals and mechanisms. Cell. 1991 Jul 12;66(1):15–22. doi: 10.1016/0092-8674(91)90135-l. [DOI] [PubMed] [Google Scholar]
  17. Nishimura T., Vogt P. K. The avian cellular homolog of the oncogene jun. Oncogene. 1988 Dec;3(6):659–663. [PubMed] [Google Scholar]
  18. Rihs H. P., Jans D. A., Fan H., Peters R. The rate of nuclear cytoplasmic protein transport is determined by the casein kinase II site flanking the nuclear localization sequence of the SV40 T-antigen. EMBO J. 1991 Mar;10(3):633–639. doi: 10.1002/j.1460-2075.1991.tb07991.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  20. Sanchez E. R., Toft D. O., Schlesinger M. J., Pratt W. B. Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein. J Biol Chem. 1985 Oct 15;260(23):12398–12401. [PubMed] [Google Scholar]
  21. Silver P. A. How proteins enter the nucleus. Cell. 1991 Feb 8;64(3):489–497. doi: 10.1016/0092-8674(91)90233-o. [DOI] [PubMed] [Google Scholar]
  22. Staufenbiel M., Deppert W. Preparation of nuclear matrices from cultured cells: subfractionation of nuclei in situ. J Cell Biol. 1984 May;98(5):1886–1894. doi: 10.1083/jcb.98.5.1886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES