|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 105, Issue 3 799-806, Copyright © 1993 by Company of Biologists
JOURNAL ARTICLES |
MS Schmidt-Zachmann and EA Nigg
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Nucleolin, a major nucleolar phosphoprotein, is presumed to function in rDNA transcription, rRNA packaging and ribosome assembly. Its primary sequence was highly conserved during evolution and suggests a multi-domain structure. To identify structural elements required for nuclear uptake and nucleolar accumulation of nucleolin, we used site-directed mutagenesis to introduce point- and deletion-mutations into a chicken nucleolin cDNA. Following transient expression in mammalian cells, the intracellular distribution of the corresponding wild-type and mutant proteins was determined by indirect immunofluorescence microscopy. We found that nucleolin contains a functional nuclear localization signal (KRKKEMANKSAPEAKKKK) that conforms exactly to the consensus proposed recently for a bipartite signal (Robbins, J., Dilworth, S.M., Laskey, R.A. and Dingwall, C. (1991) Cell 64, 615-623). Concerning nucleolar localization, we found that the N-terminal 250 amino acids of nucleolin are dispensible, but deletion of either the centrally located RNA-binding motifs (the RNP domain) or the glycine/arginine-rich C terminus (the GR domain) resulted in an exclusively nucleoplasmic distribution. Although both of these latter domains were required for correct subcellular localization of nucleolin, they were not sufficient to target non-nucleolar proteins to the nucleolus. From these results we conclude that nucleolin does not contain a single, linear nucleolar targeting signal. Instead, we propose that the protein uses a bipartite NLS to enter the nucleus and then accumulates within the nucleolus by virtue of binding to other nucleolar components (probably rRNA) via its RNP and GR domains.
This article has been cited by other articles:
|
|
 |
|
  J. J. Petricka and T. M. Nelson Arabidopsis Nucleolin Affects Plant Development and Patterning Plant Physiology, May 1, 2007; 144(1): 173 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rickards, S. J. Flint, M. D. Cole, and G. LeRoy Nucleolin Is Required for RNA Polymerase I Transcription In Vivo Mol. Cell. Biol., February 1, 2007; 27(3): 937 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Goyal, D. Pandey, and W. Siess Phosphorylation-dependent Regulation of Unique Nuclear and Nucleolar Localization Signals of LIM Kinase 2 in Endothelial Cells J. Biol. Chem., September 1, 2006; 281(35): 25223 - 25230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Torrano, J. Navascues, F. Docquier, R. Zhang, L. J. Burke, I. Chernukhin, D. Farrar, J. Leon, M. T. Berciano, R. Renkawitz, et al. Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism J. Cell Sci., May 1, 2006; 119(9): 1746 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Renvoise, K. Khoobarry, M.-C. Gendron, C. Cibert, L. Viollet, and S. Lefebvre Distinct domains of the spinal muscular atrophy protein SMN are required for targeting to Cajal bodies in mammalian cells J. Cell Sci., February 15, 2006; 119(4): 680 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kim, D. D. Dimitrova, K. M. Carta, A. Saxena, M. Daras, and J. A. Borowiec Novel Checkpoint Response to Genotoxic Stress Mediated by Nucleolin-Replication Protein A Complex Formation Mol. Cell. Biol., March 15, 2005; 25(6): 2463 - 2474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Horke, K. Reumann, M. Schweizer, H. Will, and T. Heise Nuclear Trafficking of La Protein Depends on a Newly Identified Nucleolar Localization Signal and the Ability to Bind RNA J. Biol. Chem., June 18, 2004; 279(25): 26563 - 26570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Eilbracht, M. Reichenzeller, M. Hergt, M. Schnolzer, H. Heid, M. Stohr, W. W. Franke, and M. S. Schmidt-Zachmann NO66, a Highly Conserved Dual Location Protein in the Nucleolus and in a Special Type of Synchronously Replicating Chromatin Mol. Biol. Cell, April 1, 2004; 15(4): 1816 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Christian, J. Pilch, M. E. Akerman, K. Porkka, P. Laakkonen, and E. Ruoslahti Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels J. Cell Biol., November 24, 2003; 163(4): 871 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Da Costa, G. Tchernia, P. Gascard, A. Lo, J. Meerpohl, C. Niemeyer, J.-A. Chasis, J. Fixler, and N. Mohandas Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology Blood, June 15, 2003; 101(12): 5039 - 5045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Mathieu, Y. Yukawa, J.-L. Prieto, I. Vaillant, M. Sugiura, and S. Tourmente Identification and characterization of transcription factor IIIA and ribosomal protein L5 from Arabidopsis thaliana Nucleic Acids Res., May 1, 2003; 31(9): 2424 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Rogers, S. Gupta, S. E. Welty, T. N. Hansen, and C. V. Smith Nuclear and Nucleolar Glutathione Reductase, Peroxidase, and Transferase Activities in Livers of Male and Female Fischer-344 Rats Toxicol. Sci., September 1, 2002; 69(1): 279 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wurm, H. Chen, T. Hodgson, P. Britton, G. Brooks, and J. A. Hiscox Localization to the Nucleolus Is a Common Feature of Coronavirus Nucleoproteins, and the Protein May Disrupt Host Cell Division J. Virol., October 1, 2001; 75(19): 9345 - 9356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Scott, F.-M. Boisvert, D. Vieyra, R. N. Johnston, D. P. Bazett-Jones, and K. Riabowol UV induces nucleolar translocation of ING1 through two distinct nucleolar targeting sequences Nucleic Acids Res., May 15, 2001; 29(10): 2052 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Eilbracht and M. S. Schmidt-Zachmann Identification of a sequence element directing a protein to nuclear speckles PNAS, March 27, 2001; 98(7): 3849 - 3854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Giesen, K. Radsak, and E. Bogner The potential terminase subunit of human cytomegalovirus, pUL56, is translocated into the nucleus by its own nuclear localization signal and interacts with importin {alpha} J. Gen. Virol., September 1, 2000; 81(9): 2231 - 2244. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Tamanini, L. L. Kirkpatrick, J. Schonkeren, L. v. Unen, C. Bontekoe, C. Bakker, D. L. Nelson, H. Galjaard, B. A. Oostra, and A. T. Hoogeveen The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins Hum. Mol. Genet., June 12, 2000; 9(10): 1487 - 1493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Falzon and P. Du Enhanced Growth of MCF-7 Breast Cancer Cells Overexpressing Parathyroid Hormone-Related Peptide Endocrinology, May 1, 2000; 141(5): 1882 - 1892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rosorius, B. Fries, R. H. Stauber, N. Hirschmann, D. Bevec, and J. Hauber Human Ribosomal Protein L5 Contains Defined Nuclear Localization and Export Signals J. Biol. Chem., April 14, 2000; 275(16): 12061 - 12068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Klein, J. A. Carroll, Y. Chen, M. F. Henry, P. A. Henry, I. E. Ortonowski, G. Pintucci, R. C. Beavis, W. H. Burgess, and D. B. Rifkin Biochemical Analysis of the Arginine Methylation of High Molecular Weight Fibroblast Growth Factor-2 J. Biol. Chem., February 4, 2000; 275(5): 3150 - 3157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Hoek, M Engstler, and G. Cross Expression-site-associated gene 8 (ESAG8) of Trypanosoma brucei is apparently essential and accumulates in the nucleolus J. Cell Sci., January 11, 2000; 113(22): 3959 - 3968. [Abstract] [PDF]
|
|
|
|
|
|
J. Bolivar, I. Diaz, C. Iglesias, and M. M. Valdivia Molecular Cloning of a Zinc Finger Autoantigen Transiently Associated with Interphase Nucleolus and Mitotic Centromeres and Midbodies. ORTHOLOGOUS PROTEINS WITH NINE CXXC MOTIFS HIGHLY CONSERVED FROM NEMATODES TO HUMANS J. Biol. Chem., December 17, 1999; 274(51): 36456 - 36464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ceman, V. Brown, and S. T. Warren Isolation of an FMRP-Associated Messenger Ribonucleoprotein Particle and Identification of Nucleolin and the Fragile X-Related Proteins as Components of the Complex Mol. Cell. Biol., December 1, 1999; 19(12): 7925 - 7932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Clau{beta}en, F. Rudt, and T. Pieler Functional Modules in Ribosomal Protein L5 for Ribonucleoprotein Complex Formation and Nucleocytoplasmic Transport J. Biol. Chem., November 26, 1999; 274(48): 33951 - 33958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Jarrous, J. S. Wolenski, D. Wesolowski, C. Lee, and S. Altman Localization in the Nucleolus and Coiled Bodies of Protein Subunits of the Ribonucleoprotein Ribonuclease P J. Cell Biol., August 9, 1999; 146(3): 559 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamada, Y.-M. Jiang, H.-Y. Zhu, K. Inagaki-Ohara, and Y. Nishiyama Nucleolar localization of the UL3 protein of herpes simplex virus type 2 J. Gen. Virol., August 1, 1999; 80(8): 2157 - 2164. [Abstract] [Full Text]
|
|
|
|
|
|
A. M. Fry, L. Arnaud, and E. A. Nigg Activity of the Human Centrosomal Kinase, Nek2, Depends on an Unusual Leucine Zipper Dimerization Motif J. Biol. Chem., June 4, 1999; 274(23): 16304 - 16310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Hanakahi, H. Sun, and N. Maizels High Affinity Interactions of Nucleolin with G-G-paired rDNA J. Biol. Chem., May 28, 1999; 274(22): 15908 - 15912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tanaka and E. A. Nigg Cloning and Characterization of the Murine Nek3 Protein Kinase, a Novel Member of the NIMA Family of Putative Cell Cycle Regulators J. Biol. Chem., May 7, 1999; 274(19): 13491 - 13497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Aarts, D. Levy, B. He, S. Stregger, T. Chen, S. Richard, and J. E. Henderson Parathyroid Hormone-related Protein Interacts with RNA J. Biol. Chem., February 19, 1999; 274(8): 4832 - 4838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Zhang, C Herrmann, and F Grosse Nucleolar localization of murine nuclear DNA helicase II (RNA helicase A) J. Cell Sci., January 8, 1999; 112(16): 2693 - 2703. [Abstract] [PDF]
|
|
|
|
|
|
H Ginisty, H Sicard, B Roger, and P Bouvet Structure and functions of nucleolin J. Cell Sci., January 3, 1999; 112(6): 761 - 772. [Abstract] [PDF]
|
|
|
|
|
|
P. Bouvet, J.-J. Diaz, K. Kindbeiter, J.-J. Madjar, and F. Amalric Nucleolin Interacts with Several Ribosomal Proteins through Its RGG Domain J. Biol. Chem., July 24, 1998; 273(30): 19025 - 19029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Fry, T. Mayor, P. Meraldi, Y.-D. Stierhof, K. Tanaka, and E. A. Nigg C-Nap1, a Novel Centrosomal Coiled-Coil Protein and Candidate Substrate of the Cell Cycle-regulated Protein Kinase Nek2 J. Cell Biol., June 29, 1998; 141(7): 1563 - 1574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Lee, S. C. Chang, C.-J. Chen, and M.-F. Chang The Nucleolin Binding Activity of Hepatitis Delta Antigen Is Associated with Nucleolus Targeting J. Biol. Chem., March 27, 1998; 273(13): 7650 - 7656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. P. Ivanov, K. Simin, A. Letsou, J. F. Atkins, and R. F. Gesteland The Drosophila Gene for Antizyme Requires Ribosomal Frameshifting for Expression and Contains an Intronic Gene for snRNP Sm D3 on the Opposite Strand Mol. Cell. Biol., March 1, 1998; 18(3): 1553 - 1561. [Abstract] [Full Text]
|
|
|
|
|
|
N Fomproix, J Gebrane-Younes, and D Hernandez-Verdun Effects of anti-fibrillarin antibodies on building of functional nucleoli at the end of mitosis J. Cell Sci., January 2, 1998; 111(3): 359 - 372. [Abstract] [PDF]
|
|
|
|
|
|
H. Pluk, J. Soffner, R. Lührmann, and W. J. v. Venrooij cDNA Cloning and Characterization of the Human U3 Small Nucleolar Ribonucleoprotein Complex-Associated 55-Kilodalton Protein Mol. Cell. Biol., January 1, 1998; 18(1): 488 - 498. [Abstract] [Full Text]
|
|
|
|
|
|
M. S. Schmidt-Zachmann, S. Knecht, and A. Krämer Molecular Characterization of a Novel, Widespread Nuclear Protein That Colocalizes with Spliceosome Components Mol. Biol. Cell, January 1, 1998; 9(1): 143 - 160. [Abstract] [Full Text]
|
|
|
|
|
|
R. F. Zirwes, M. S. Schmidt-Zachmann, and W. W. Franke Identification of a small, very acidic constitutive nucleolar protein (NO29) as a member of the nucleoplasmin family PNAS, October 14, 1997; 94(21): 11387 - 11392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Blangy, L. Arnaud, and E. A. Nigg Phosphorylation by p34cdc2 Protein Kinase Regulates Binding of the Kinesin-related Motor HsEg5 to the Dynactin Subunit p150Glued J. Biol. Chem., August 1, 1997; 272(31): 19418 - 19424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Caceres, T. Misteli, G. R. Screaton, D. L. Spector, and A. R. Krainer Role of the Modular Domains of SR Proteins in Subnuclear Localization and Alternative Splicing Specificity J. Cell Biol., July 28, 1997; 138(2): 225 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Hanakahi, L. A. Dempsey, M.-J. Li, and N. Maizels Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein, LR1 PNAS, April 15, 1997; 94(8): 3605 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Russo, G. Ricciardelli, and C. Pietropaolo Different Domains Cooperate to Target the Human Ribosomal L7a Protein to the Nucleus and to the Nucleoli J. Biol. Chem., February 21, 1997; 272(8): 5229 - 5235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Carotenuto, G Maturi, V Infante, T Capriglione, T. Petrucci, and C Campanella A novel protein cross-reacting with antibodies against spectrin is localised in the nucleoli of amphibian oocytes J. Cell Sci., January 11, 1997; 110(21): 2683 - 2690. [Abstract] [PDF]
|
|
|
|
|
|
F Bachelerie, M. Rodriguez, C Dargemont, D Rousset, D Thomas, J. Virelizier, and F Arenzana-Seisdedos Nuclear export signal of IkappaBalpha interferes with the Rev-dependent posttranscriptional regulation of human immunodeficiency virus type I J. Cell Sci., January 11, 1997; 110(22): 2883 - 2893. [Abstract] [PDF]
|
|
|
|
|
|
R. Golsteyn, M. Beckerle, T Koay, and E Friederich Structural and functional similarities between the human cytoskeletal protein zyxin and the ActA protein of Listeria monocytogenes J. Cell Sci., January 8, 1997; 110(16): 1893 - 1906. [Abstract] [PDF]
|
|
|
|
|
|
D. A. Jans, P. Jans, L. J. Briggs, V. Sutton, and J. A. Trapani Nuclear Transport of Granzyme B (Fragmentin-2). DEPENDENCE ON PERFORIN IN VIVO AND CYTOSOLIC FACTORS IN VITRO J. Biol. Chem., November 29, 1996; 271(48): 30781 - 30789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Louie, K. A. Resing, T. S. Lewis, and N. G. Ahn Mass Spectrometric Analysis of 40 S Ribosomal Proteins from Rat-1 Fibroblasts J. Biol. Chem., November 8, 1996; 271(45): 28189 - 28198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Michael and G. Dreyfuss Distinct Domains in Ribosomal Protein L5 Mediate 5 S rRNA Binding and Nucleolar Localization J. Biol. Chem., May 10, 1996; 271(19): 11571 - 11574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Hennekes and E. Nigg The role of isoprenylation in membrane attachment of nuclear lamins. A single point mutation prevents proteolytic cleavage of the lamin A precursor and confers membrane binding properties J. Cell Sci., January 4, 1994; 107(4): 1019 - 1029. [Abstract] [PDF]
|
|
|
|
|
|
H. van Eenennaam, D. Lugtenberg, J. H. P. Vogelzangs, W. J. van Venrooij, and G. J. M. Pruijn hPop5, a Protein Subunit of the Human RNase MRP and RNase P Endoribonucleases J. Biol. Chem., August 17, 2001; 276(34): 31635 - 31641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Waggener and P. J. DiMario Two Splice Variants of Nopp140 in Drosophila melanogaster Mol. Biol. Cell, January 1, 2002; 13(1): 362 - 381. [Abstract] [Full Text] [PDF]
|
|
