ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 8 (2010), No 3, p 141-150
DOI 10.2478/v10136-009-0017-5

Nucleolin, a major conserved multifunctional nucleolar phosphoprotein of proliferating cells

Francisco Javier Medina, Fernando Gonzalez-Camacho, Ana Isabel Manzano, Antonio Manrique, Raul Herranz

Address: Francisco Javier Medina, Centro de Investigaciones Biologicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
fjmedina@cib.csic.es

Received 15th March 2010.
Revised 7th May 2010.
Published online 10th May 2010.

Full text article (pdf)
Full text article (html)
Abstract in xml format

SUMMARY
Nucleolin is the major nucleolar protein of animal, plant and yeast proliferating cells. It is enriched in the most soluble nuclear or nucleolar protein extract, containing ribonucleoproteins, from which it has been purified. It has a tripartite structure in which each domain accounts for different functions. Despite its multifunctionality, the best characterized role of nucleolin is in the primary cleavage of pre-rRNA, an early step of ribosome biogenesis. In the nucleolus of proliferating cells, nucleolin is mostly located in the dense fibrillar component, following a vectorial pattern, from the periphery of fibrillar centers outwards. This pattern is lost in quiescent cells in which nucleolin is present in low levels. Nucleolin is the most phosphorylated protein of the soluble nuclear extract. It is phosphorylated by casein kinase II and CDKA, and phosphorylation is closely associated with the role of nucleolin in proliferating cells. During mitosis, nucleolin is transported from the mother to the daughter cell nucleolus in the form of processing particles, together with pre-rRNA precursors and other nucleolar proteins. It forms part of prenucleolar bodies and plays a role in nucleologenesis. Recent studies on the nucleolin function, carried out on samples with inactivated nucleolin genes (siRNA downregulated or mutants) have evidenced that nucleolin is absolutely essential for cell proliferation, for the organization of the nucleolus and for transcription and processing of pre-rRNA. In plants, nucleolin controls the auxin responsiveness, thus being involved in the regulation of plant development.

KEY WORDS
ribosome biogenesis; pre-rRNA processing; protein kinases; cell cycle; prenucleolar bodies; auxin

REFERENCES
Angelier N, Tramier M, Louvet E, Coppey-Moisan M, Savino TM, De Mey JR, Hernandez-Verdun D: Tracking the interactions of rRNA processing proteins during nucleolar assembly in living cells. Mol Biol Cell 16:2862-2871, 2005.

Belenguer P, Caizergues-Ferrer M, Labbe JC, Doree M, Amalric F: Mitosis-specific phosphorylation of nucleolin by p34 cdc2 protein kinase. Mol Cell Biol 10:3607-3618, 1990.

Bernstein KA, Bleichert F, Bean JM, Cross FR, Baserga SJ: Ribosome biogenesis is sensed at the start cell cycle checkpoint. Mol Biol Cell 18:953-964, 2007.

Bogre L, Jonak C, Mink M, Meskiene I, Traas J, Ha DTC, Swoboda I, Plank C, Wagner E, Heberle-Bors E, Hirt H: Developmental and cell cycle regulation of alfalfa NucMs1, a plant homolog of the yeast NSR1 and mammalian nucleolin. Plant Cell 8:417-428, 1996.

Bouvet P, Diaz JJ, Kindbeiter K, Madjar JJ, Amalric F: Nucleolin interacts with several ribosomal proteins through its RGG domain. J Biol Chem 273:19025-19029, 1998.

Bugler B, Caizergues-Ferrer M, Bouche G, Bourbon HM, Amalric F: Detection and localization of a class of proteins immunologically related to a 100-kDa nucleolar protein. Eur J Biochem 128:475-480, 1982.

Busch H, Ballal NR, Rao MRS, Choi YC: Factors affecting nucleolar rDNA readouts. In Rothblum LI, Busch H (eds.): The Cell Nucleus, vol 5, Chromatin, part b, Academic Press, New York, San Francisco, London 1978, pp. 416-468.

Caizergues-Ferrer M, Belenguer P, Lapeyre B, Amalric F, Wallace MO, Olson MOJ: Phosphorylation of nucleolin by a nuclear type NII protein kinase. Biochemistry 26:7876-7883, 1987.

Cerdido A, Medina FJ: Subnucleolar location of fibrillarin and variation in its levels during the cell cycle and during differentiation of plant cells. Chromosoma 103:625-634, 1995.

Chan EKL, Imai H, Hamel JC, Tan EM: Human autoantibody to RNA polymerase I transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR-90 and ribosomal RNA transcription upstream binding factor. J Exp Med 174:1239-1244, 1991.

De Carcer G, Medina FJ: Simultaneous localization of transcription and early processing markers allows dissection of functional domains in the plant cell nucleolus. J Struct Biol 128:139-151, 1999.

De Carcer G, Cerdido A, Medina FJ: Nopa64, a novel nucleolar phosphoprotein from proliferating onion cells, sharing immunological determinants with mammalian nucleolin. Planta 201:487-495, 1997.

Dundr M, Misteli T, Olson MOJ: The dynamics of postmitotic reassembly of the nucleolus. J Cell Biol 150:433-446, 2000.

Escande ML, Gas N, Stevens BJ: Immunolocalization of the 100 k nucleolar protein in CHO cells. Biol Cell 53:99-110, 1985.

Ghisolfi L, Joseph G, Amalric F, Erard M: The glycine-rich domain of nucleolin has an unusual supersecondary structure responsible for its RNA-helix-destabilizing properties. J Biol Chem 267:2955-2959, 1992.

Ginisty H, Sicard H, Roger B, Bouvet P: Structure and functions of nucleolin. J Cell Sci 112:761-772, 1999.

Ginisty H, Serin G, Ghisolfi-Nieto L, Roger B, Libante V, Amalric F, Bouvet P: Interaction of nucleolin with an evolutionarily conserved pre-ribosomal RNA sequence is required for the assembly of the primary processing complex. J Biol Chem 275:18845-18850, 2000.

Gonzalez-Camacho F, Medina FJ: Identification of specific plant nucleolar phosphoproteins in a functional proteomic analysis Proteomics 4:407-417, 2004.

Gonzalez-Camacho F, Medina FJ: Extraction of nuclear proteins from root meristematic cells. In Thiellement H, Zivy M, Damerval C, Mechin V (eds.): Plant Proteomics: Methods and Protocols, Humana Press, Totowa, NJ 2006a, pp. 63-72.

Gonzalez-Camacho F, Medina FJ: The nucleolar structure and the activity of nucleolin-like protein NopA100 during the cell cycle in proliferating plant cells. Histochem Cell Biol 125:139-153, 2006b.

Hernandez-Verdun D, Roussel P: Regulators of nucleolar functions. Prog Cell Cycle Res 5:301-308, 2003.

Inze D, De Veylder L: Cell cycle regulation in plant development. Annu Rev Genet 40:77-105, 2006.

Jimenez-Garcia LF, Rothblum LI, Busch H, Ochs RL: Nucleologenesis:Use of non-isotopic "in situ" hybridization and immunocytochemistry to compare the localization of rDNA and nucleolar proteins during mitosis. Biol Cell 65:239-246, 1989.

Klein J, Grummt I: Cell cycle-dependent regulation of RNA polymerase I transcription: The nucleolar transcription factor UBF is inactive in mitosis and early G1. Proc Natl Acad Sci USA 96:6096-6101, 1999.

Kojima H, Suzuki T, Kato T, Enomoto K, Sato S, Kato T, Tabata S, Saez-Vasquez J, Echeverria M, Nakagawa T, Ishiguro S, Nakamura K: Sugar-inducible expression of the nucleolin-1 gene of Arabidopsis thaliana and its role in ribosome synthesis, growth and development. Plant J 49:1053-1063, 2007.

Kondo K, Inouye M: Yeast NSR1 protein that has structural similarity to mammalian nucleolin is involved in pre-rRNA processing. J Biol Chem 267:16252-16258, 1992.

Lapeyre B, Bourbon HM, Amalric F: Nucleolin, the major nucleolar protein of growing eukaryotic cells: An unusual protein structure revealed by the nucleotide sequence. Proc Natl Acad Sci USA 84:1472-1476, 1987.

Ma N, Matsunaga S, Takata H, Ono-Maniwa R, Uchiyama S, Fukui K: Nucleolin functions in nucleolus formation and chromosome congression. J Cell Sci 120:2091-2105, 2007.

Magyar Z, De Veylder L, Atanassova L, Bako L, Inze D, Bogre L: The role of Arabidopsis E2FB transcription factor in regulating auxin-dependent cell division. Plant Cell 17:2527-2541, 2005.

Martin M, Medina FJ: A Drosophila anti-RNA polymerase II antibody recognizes a plant nucleolar antigen, RNA polymerase I, which is mostly localized in fibrillar centres. J Cell Sci 100:99-107, 1991.

Martin M, Garcia-Fernandez LF, Moreno Diaz de la Espina S, Noaillac-Depeyre J, Gas N, Medina FJ: Identification and localization of a nucleolin homologue in onion nucleoli. Exp Cell Res 199:74-84, 1992.

Matia I, Gonzalez-Camacho F, Herranz R, Kiss JZ, Gasset G, van Loon JJWA, Marco R, Medina FJ: Plant cell proliferation and growth are altered by microgravity conditions in spaceflight. J Plant Physiol 167:184-193 2010.

Medina FJ, Gonzalez-Camacho F: Nucleolar proteins and cell proliferation in plant cells. Recent Res Dev Plant Biol 3:55-68, 2003.

Medina FJ, Herranz R: Microgravity environment uncouples cell growth and cell proliferation in root meristematic cells: The mediator role of auxin. Plant Signal Behav 5:176-179, 2010.

Medina FJ, Cerdido A, Fernandez-Gomez ME: Components of the nucleolar processing complex (pre-rRNA, fibrillarin and nucleolin) colocalize during mitosis and are incorporated to daughter cell nucleoli. Exp Cell Res 221:111-125, 1995.

Medina FJ, Cerdido A, De Carcer G: The functional organization of the nucleolus in proliferating plant cells. Eur J Histochem 44:117-131, 2000.

Minguez A, Moreno Diaz de la Espina S: In situ localization of nucleolin in the plant nucleolar matrix. Exp Cell Res 222:171-178, 1996.

Mizukami Y: A matter of size: Developmental control of organ size in plants. Curr Opin Plant Biol 4:533-539, 2001.

Olson MOJ: The role of proteins in nucleolar structure and function. In Strauss PR, Wilson SH (eds.): The Eukaryotic Nucleus Molecular Biochemistry and Macromolecular Assemblies, The Telford Press, Caldwell, New Jersey 1991, pp. 519-559.

Petricka JJ, Nelson TM: Arabidopsis nucleolin affects plant development and patterning. Plant Physiol 144:173-186, 2007.

Pontvianne F, Matia I, Douet J, Tourmente S, Medina FJ, Echeverria M, Saez-Vasquez J: Characterization of AtNUC-L1 reveals a central role of nucleolin in nucleolus organization and silencing of AtNUC-L2 gene in Arabidopsis. Mol Biol Cell 18:369-379, 2007.

Reichler SA, Balk J, Brown ME, Woodruff K, Clark GB, Roux SJ: Light differentially regulates cell division and the mRNA abundance of pea nucleolin during de-etiolation. Plant Physiol 125:339-350, 2001.

Risueno MC, Moreno Diaz de la Espina S: Ultrastructural and cytochemical study of the quiescent root meristematic cell nucleus. J Submicrosc Cytol 11:85-98, 1979.

Risueno MC, Medina FJ: The nucleolar structure in plant cells. University of the Basque Country-Springer International, Leioa 1986, 1-154 pp.

Rodrigo RM, Rendon MC, Torreblanca J, Garcia-Herdugo G, Moreno FJ: Characterization and immunolocalization of RNA polymerase I transcription factor UBF with anti-NOR serum in Protozoa, higher plant and vertebrate cells. J Cell Sci 103:1053-1063, 1992.

Roger B, Moisand A, Amalric F, Bouvet P: Nucleolin provides a link between RNA polymerase I transcription and pre-ribosome assembly. Chromosoma 111:399-407, 2003.

Saez-Vasquez J, Medina FJ: The plant nucleolus. In Kader JC, Delseny M (eds.): Advances in Botanical Research, vol 47, Elsevier, San Diego, CA 2008, pp. 1-46.

Saez-Vasquez J, Caparros-Ruiz D, Barneche F, Echeverria M: A plant snoRNP complex containing snoRNAs, fibrillarin, and nucleolin-like proteins is competent for both rRNA gene binding and pre-rRNA processing in vitro. Mol Cell Biol 24:7284-7297, 2004.

Savino TM, Gebrane-Younes J, De Mey J, Sibarita J-B, Hernandez-Verdun D: Nucleolar assembly of the rRNA processing machinery in living cells. J Cell Biol 153:1097-1110, 2001.

Serin G, Joseph G, Faucher C, Ghisolfi L, Bouche G, Amalric F, Bouvet P: Localization of nucleolin binding sites on human and mouse pre- ribosomal RNA. Biochimie 78:530-538, 1996.

Shaw PJ, Jordan EG: The nucleolus. Annu Rev Cell Biol 11:93-121, 1995.

Storck S, Thiry M, Bouvet P: Conditional knockout of nucleolin in DT40 cells reveals the functional redundancy of its RNA-binding domains. Biol Cell 101:153-167, 2009.

Ueda J, Miyamoto K, Yuda T, Hoshino T, Fujii S, Mukai C, Kamigaichi S, Aizawa S, Yoshizaki I, Shimazu T, Fukui K: Growth and development, and auxin polar transport in higher plants under microgravity conditions in space: Bric-aux on STS-95 space experiment. J Plant Res 112:487-492, 1999.

Ugrinova I, Monier K, Ivaldi C, Thiry M, Storck S, Mongelard F, Bouvet P: Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication. BMC Mol Biol 8:66, 2007.
CITED

Picmonova V, Berger J. Genistein effects on haematoimmune cells in a newly developed alternative toxicological model. Exp Toxicol Pathol. 64: 411-415, 2012.

Smetana K. The nucleolus through the years. J Appl Biomed. 9: 119-127, 2011.

Berger J. The age of biomedicine: current trends in traditional subjects. J Appl Biomed. 9: 57-61, 2011.

Garcia MC, Williams J, Johnson K, Olden K, Roberts JD. Arachidonic acid stimulates formation of a novel complex containing nucleolin and RhoA. FEBS Lett. 585: 618-622, 2011.

BACK