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PMID: 1656223 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A hydrophobic protein sequence can override a nuclear localization signal independently of protein context.

Molecular and cellular biology ·Vol. 11 ·No. 10 ·1991-10-00 ·Pages 5137-46

van Zee K, Appel F, Fanning E

Abstract

Simian virus 40 T antigen is specifically targeted to the nucleus by the signal Pro-Lys-Lys-128-Lys-Arg-Lys-Val. We have previously described the isolation of a simian virus 40 T-antigen mutant, 676FS, which retains a wild-type nuclear localization signal but fails to accumulate properly in the nucleus and interferes with the nuclear localization of heterologous proteins. Here we report that the hydrophobic carboxy-terminal sequence novel to 676FS T antigen overrides the nuclear localization signal if fused to other proteins, thereby anchoring the proteins in the cytoplasm. We discuss possible mechanisms by which missorting of such a fusion protein could interfere with the nuclear transport of heterologous proteins.

MeSH Terms
Amino Acid Sequence Antigens, Polyomavirus Transforming/chemistry,genetics,metabolism Cell Line Cell Nucleus/metabolism Fluorescent Antibody Technique Molecular Sequence Data Mutation/genetics Nuclear Proteins/metabolism Protein Sorting Signals/metabolism Recombinant Fusion Proteins/metabolism Simian virus 40/genetics,metabolism beta-Galactosidase/genetics
Chemicals
Antigens, Polyomavirus Transforming Nuclear Proteins Protein Sorting Signals Recombinant Fusion Proteins beta-Galactosidase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
van Zee K
Institute for Biochemistry, Munich, Germany.
Appel F
Fanning E
References (56)
56 references, click to expand
  1. Mutations in the phosphorylation sites of simian virus 40 (SV40) T antigen alter its origin DNA-binding specificity for sites I or II and affect SV40 DNA replication activity.
    J Virol. 1988 May;62(5):1598-605 PMID: 3357207
  2. SV40-transformed simian cells support the replication of early SV40 mutants.
    Cell. 1981 Jan;23(1):175-82 PMID: 6260373
  3. A short amino acid sequence able to specify nuclear location.
    Cell. 1984 Dec;39(3 Pt 2):499-509 PMID: 6096007
  4. Amino terminus of the yeast GAL4 gene product is sufficient for nuclear localization.
    Proc Natl Acad Sci U S A. 1984 Oct;81(19):5951-5 PMID: 6091123
  5. Pentapeptide nuclear localization signal in adenovirus E1a.
    Mol Cell Biol. 1987 Jul;7(7):2451-6 PMID: 3614197
  6. An N-ethylmaleimide-sensitive cytosolic factor necessary for nuclear protein import: requirement in signal-mediated binding to the nuclear pore.
    J Cell Biol. 1990 Mar;110(3):547-57 PMID: 2307698
  7. How proteins enter the nucleus.
    Cell. 1991 Feb 8;64(3):489-97 PMID: 1991319
  8. Nuclear protein localization.
    Biochim Biophys Acta. 1991 Mar 7;1071(1):83-101 PMID: 2004116
  9. A nuclear localization signal binding protein in the nucleolus.
    J Cell Biol. 1990 Dec;111(6 Pt 1):2235-45 PMID: 2177472
  10. Cytoplasmic transport of ribosomal subunits microinjected into the Xenopus laevis oocyte nucleus: a generalized, facilitated process.
    J Cell Biol. 1990 Oct;111(4):1571-82 PMID: 2211825
  11. Multiple pathways in nuclear transport: the import of U2 snRNP occurs by a novel kinetic pathway.
    J Cell Biol. 1991 Jan;112(2):215-23 PMID: 1824847
  12. The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen.
    J Cell Biol. 1988 Sep;107(3):841-9 PMID: 3417784
  13. Identification of specific binding proteins for a nuclear location sequence.
    Nature. 1989 Jan 19;337(6204):276-9 PMID: 2911368
  14. Nucleocytoplasmic transport of ribosomes in a eukaryotic system: is there a facilitated transport process?
    Proc Natl Acad Sci U S A. 1989 Mar;86(6):1791-5 PMID: 2648382
  15. Identification of four nuclear transport signal-binding proteins that interact with diverse transport signals.
    Mol Cell Biol. 1989 Jul;9(7):3028-36 PMID: 2550792
  16. Nuclear location signal-mediated protein transport.
    Biochim Biophys Acta. 1989 Aug 14;1008(3):263-80 PMID: 2667641
  17. Induction of nuclear transport with a synthetic peptide homologous to the SV40 T antigen transport signal.
    Cell. 1986 Aug 15;46(4):575-82 PMID: 3015419
  18. Synthetic peptides as nuclear localization signals.
    Nature. 1986 Aug 14-20;322(6080):641-4 PMID: 3638500
  19. The nucleus: structure, function, and dynamics.
    Annu Rev Biochem. 1987;56:535-65 PMID: 3304144
  20. Nuclear protein migration involves two steps: rapid binding at the nuclear envelope followed by slower translocation through nuclear pores.
    Cell. 1988 Mar 11;52(5):655-64 PMID: 3125984
  21. Nuclear import can be separated into distinct steps in vitro: nuclear pore binding and translocation.
    Cell. 1988 Mar 11;52(5):641-53 PMID: 3345567
  22. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor.
    EMBO J. 1987 Nov;6(11):3333-40 PMID: 3123217
  23. Transactivation of gene expression by nuclear and cytoplasmic rel proteins.
    Mol Cell Biol. 1989 Oct;9(10):4323-36 PMID: 2555689
  24. Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1203-7 PMID: 2919169
  25. A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo.
    Cell. 1989 Dec 22;59(6):1189-202 PMID: 2688897
  26. Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function.
    Cell. 1989 Dec 22;59(6):1179-88 PMID: 2598266
  27. The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila.
    Cell. 1989 Dec 22;59(6):1165-77 PMID: 2598265
  28. Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport.
    Cell. 1986 Sep 12;46(6):939-50 PMID: 3757030
  29. Cell-dependent efficiency of reiterated nuclear signals in a mutant simian virus 40 oncoprotein targeted to the nucleus.
    Mol Cell Biol. 1988 Dec;8(12):5495-503 PMID: 2854199
  30. A mutant SV40 large T antigen interferes with nuclear localization of a heterologous protein.
    Cell. 1988 Jul 1;54(1):117-25 PMID: 2838177
  31. Allosteric control of simian virus 40 T-antigen binding to viral origin DNA.
    J Virol. 1986 Jun;58(3):765-72 PMID: 3009885
  32. Nuclear location signals in polyoma virus large-T.
    Cell. 1986 Jan 17;44(1):77-85 PMID: 3000623
  33. The effect of protein context on nuclear location signal function.
    Cell. 1987 Jul 31;50(3):465-75 PMID: 3038333
  34. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.
    Cell. 1988 Apr 22;53(2):211-7 PMID: 3129195
  35. I kappa B: a specific inhibitor of the NF-kappa B transcription factor.
    Science. 1988 Oct 28;242(4878):540-6 PMID: 3140380
  36. The nuclear migration signal of Xenopus laevis nucleoplasmin.
    EMBO J. 1987 Sep;6(9):2617-25 PMID: 3119324
  37. Identification of the human c-myc protein nuclear translocation signal.
    Mol Cell Biol. 1988 Oct;8(10):4048-54 PMID: 3054508
  38. Effect of basic and nonbasic amino acid substitutions on transport induced by simian virus 40 T-antigen synthetic peptide nuclear transport signals.
    Mol Cell Biol. 1988 Jul;8(7):2722-9 PMID: 3043192
  39. Nuclear localization of the adenovirus DNA-binding protein: requirement for two signals and complementation during viral infection.
    Mol Cell Biol. 1989 Oct;9(10):4372-80 PMID: 2531277
  40. Context affects nuclear protein localization in Saccharomyces cerevisiae.
    Mol Cell Biol. 1989 Feb;9(2):384-9 PMID: 2496300
  41. Nuclear transport kinetics depend on phosphorylation-site-containing sequences flanking the karyophilic signal of the Simian virus 40 T-antigen.
    EMBO J. 1989 May;8(5):1479-84 PMID: 2670556
  42. Yeast proteins that recognize nuclear localization sequences.
    J Cell Biol. 1989 Sep;109(3):983-9 PMID: 2670959
  43. Facilitated nuclear transport of histone H1 and other small nucleophilic proteins.
    Cell. 1990 Mar 23;60(6):999-1008 PMID: 1690602
  44. Cell biology of the snRNP particles.
    Crit Rev Biochem Mol Biol. 1990;25(1):1-46 PMID: 2138975
  45. PrlA (SecY) and PrlG (SecE) interact directly and function sequentially during protein translocation in E. coli.
    Cell. 1990 Jun 1;61(5):833-42 PMID: 2111734
  46. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers.
    Gene. 1982 Oct;19(3):259-68 PMID: 6295879
  47. Monoclonal antibodies specific for simian virus 40 tumor antigens.
    J Virol. 1981 Sep;39(3):861-9 PMID: 6169844
  48. Carboxy terminus of polyoma middle-sized tumor antigen is required for attachment to membranes, associated protein kinase activities, and cell transformation.
    Proc Natl Acad Sci U S A. 1982 Jun;79(11):3579-83 PMID: 6179082
  49. Intracellular transport of microinjected 5S and small nuclear RNAs.
    Nature. 1982 Feb 18;295(5850):572-7 PMID: 6173771
  50. Construction and characterization of an SV40 mutant defective in nuclear transport of T antigen.
    Cell. 1984 Jul;37(3):801-13 PMID: 6086146
  51. tRNA transport from the nucleus in a eukaryotic cell: carrier-mediated translocation process.
    Proc Natl Acad Sci U S A. 1983 Nov;80(21):6436-40 PMID: 6579529
  52. A simple method of reducing the fading of immunofluorescence during microscopy.
    J Immunol Methods. 1981;43(3):349-50 PMID: 7019347
  53. Effect of cell chromosome number on simian virus 40 replication.
    Exp Cell Res. 1973 Sep;81(1):120-6 PMID: 4357029
  54. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  55. Sequence requirements for nuclear location of simian virus 40 large-T antigen.
    Nature. 1984 Sep 6-11;311(5981):33-8 PMID: 6088992
  56. Movement of a karyophilic protein through the nuclear pores of oocytes.
    J Cell Biol. 1984 Dec;99(6):2216-22 PMID: 6501421
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1991-10-00
Pages
5137-46
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361531
Subset
IM
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