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The Dynamic Proteome of the Nucleolus

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The Nucleolus

Part of the book series: Protein Reviews ((PRON,volume 15))

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Abstract

The nucleolus is the most prominent organelle in the mammalian nucleus. It is assembled around rDNA genes and is the site of rDNA transcription and ribosome subunit assembly. However, the presence of proteins with no obvious relationship with ribosome subunit synthesis suggests additional functions for the nucleolus, such as regulation of mitosis, cell cycle progression and proliferation, many forms of stress response and biogenesis of multiple RNPs.

The high density and structural stability of the nucleolus make it a relatively easy organelle to isolate. Nucleoli can be isolated from cultured cells that are biochemically, morphologically and at least in part functionally intact. Mass spectrometry analyses have shown that thousands of proteins can be identified reproducibly in purified nucleoli. These proteins, which likely represent most of the human nucleolar proteome, show a considerable functional diversity. The many novel factors and separate classes of proteins identified support the view that the nucleolus may perform additional functions beyond its known role in ribosome subunit biogenesis. Future studies will expand our knowledge of the nucleolar proteomes in other model organisms and will provide a more detailed quantitative picture of the levels of each protein and how this changes under a range of cell growth conditions and in response to stress and other perturbations.

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References

  • Ahmad Y, Boisvert FM, Gregor P, Cobley A, Lamond AI (2009) NOPdb: nucleolar proteome database-2008 update. Nucleic Acids Res 37:D181–D184

    Article  PubMed  CAS  Google Scholar 

  • Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (2002) Directed proteomic analysis of the human nucleolus. Curr Biol 12:1–11

    Article  PubMed  Google Scholar 

  • Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (2005) Nucleolar proteome dynamics. Nature 433:77–83

    Article  PubMed  CAS  Google Scholar 

  • Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of bio­logy. The Gene Ontology Consortium. Nat Genet 25:25–29

    Article  PubMed  CAS  Google Scholar 

  • Banks SP, Johnson TC (1973) Developmental alterations in RNA synthesis in isolated mouse brain nucleoli. Biochim Biophys Acta 294:450–460

    PubMed  CAS  Google Scholar 

  • Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer EL, Studholme DJ, Yeats C, Eddy SR (2004) The Pfam protein families database. Nucleic Acids Res 32:D138–D141

    Article  PubMed  CAS  Google Scholar 

  • Bell AW, Ward MA, Blackstock WP, Freeman HN, Choudhary JS, Lewis AP, Chotai D, Fazel A, Gushue JN, Paiement J, Palcy S, Chevet E, Lafreniere-Roula M, Solari R, Thomas DY, Rowley A, Bergeron JJ (2001) Proteomics characterization of abundant Golgi membrane proteins. J Biol Chem 276:5152–5165

    Article  PubMed  CAS  Google Scholar 

  • Bertwistle D, Sugimoto M, Sherr CJ (2004) Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol Cell Biol 24:985–996

    Article  PubMed  CAS  Google Scholar 

  • Boisvert FM, Lamond AI (2010) p53-Dependent subcellular proteome localization following DNA damage. Proteomics 10:4087–4097

    Article  PubMed  CAS  Google Scholar 

  • Boisvert FM, van Koningsbruggen S, Navascues J, Lamond AI (2007) The multifunctional nucleolus. Nat Rev Mol Cell Biol 8:574–585

    Article  PubMed  CAS  Google Scholar 

  • Boisvert FM, Lam YW, Lamont D, Lamond AI (2010) A quantitative proteomics analysis of subcellular proteome localization and changes induced by DNA damage. Mol Cell Proteomics 9:457–470

    Article  PubMed  CAS  Google Scholar 

  • Brown JW, Shaw PJ, Shaw P, Marshall DF (2005) Arabidopsis nucleolar protein database (AtNoPDB). Nucleic Acids Res 33:D633–D636

    Article  PubMed  CAS  Google Scholar 

  • Busch H, Muramatsu M, Adams H, Steele WJ, Liau MC, Smetana K (1963) Isolation of nucleoli. Exp Cell Res 24(Suppl 9):150–163

    Article  PubMed  Google Scholar 

  • Cawood R, Harrison SM, Dove BK, Reed ML, Hiscox JA (2007) Cell cycle dependent nucleolar localization of the coronavirus nucleocapsid protein. Cell Cycle 6:863–867

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Huang S (2001) Nucleolar components involved in ribosome biogenesis cycle between the nucleolus and nucleoplasm in interphase cells. J Cell Biol 153:169–176

    Article  PubMed  CAS  Google Scholar 

  • Cheutin T, O’Donohue MF, Beorchia A, Vandelaer M, Kaplan H, Defever B, Ploton D, Thiry M (2002) Three-dimensional organization of active rRNA genes within the nucleolus. J Cell Sci 115:3297–3307

    PubMed  CAS  Google Scholar 

  • Coute Y, Burgess JA, Diaz JJ, Chichester C, Lisacek F, Greco A, Sanchez JC (2006) Deciphering the human nucleolar proteome. Mass Spectrom Rev 25:215–234

    Article  PubMed  CAS  Google Scholar 

  • Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ (2002) Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol 158:915–927

    Article  PubMed  CAS  Google Scholar 

  • Degrasse JA, Chait BT, Field MC, Rout MP (2008) High-yield isolation and subcellular proteomic characterization of nuclear and subnuclear structures from trypanosomes. Methods Mol Biol 463:77–92

    Article  PubMed  CAS  Google Scholar 

  • Dreger M, Bengtsson L, Schoneberg T, Otto H, Hucho F (2001) Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane. Proc Natl Acad Sci USA 98:11943–11948

    Article  PubMed  CAS  Google Scholar 

  • Fox AH, Bond CS, Lamond AI (2005) P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner. Mol Biol Cell 16:5304–5315

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli S, Di Cara A, Neb-Gulati A, Natt F, Schwemberger S, Hall J, Babcock GF, Bernardi R, Pandolfi PP, Thomas G (2009) Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction. Nat Cell Biol 11:501–508

    Article  PubMed  CAS  Google Scholar 

  • Gauthier DJ, Lazure C (2008) Complementary methods to assist subcellular fractionation in organellar proteomics. Expert Rev Proteomics 5:603–617

    Article  PubMed  CAS  Google Scholar 

  • Gomez SM, Nishio JN, Faull KF, Whitelegge JP (2002) The chloroplast grana proteome defined by intact mass measurements from liquid chromatography mass spectrometry. Mol Cell Proteomics 1:46–59

    Article  PubMed  CAS  Google Scholar 

  • Hall SL, Hester S, Griffin JL, Lilley KS, Jackson AP (2009) The organelle proteome of the DT40 Lymphocyte cell line. Mol Cell Proteomics 8(6):1295–1305

    Article  PubMed  CAS  Google Scholar 

  • Hinsby AM, Kiemer L, Karlberg EO, Lage K, Fausboll A, Juncker AS, Andersen JS, Mann M, Brunak S (2006) A wiring of the human nucleolus. Mol Cell 22:285–295

    Article  PubMed  CAS  Google Scholar 

  • Hirano Y, Ishii K, Kumeta M, Furukawa K, Takeyasu K, Horigome T (2009) Proteomic and targeted analytical identification of BXDC1 and EBNA1BP2 as dynamic scaffold proteins in the nucleolus. Genes Cells 14:155–166

    Article  PubMed  CAS  Google Scholar 

  • Hiscox JA (2007) RNA viruses: hijacking the dynamic nucleolus. Nat Rev Microbiol 5:119–127

    Article  PubMed  CAS  Google Scholar 

  • Hiscox JA, Whitehouse A, Matthews DA (2010) Nucleolar proteomics and viral infection. Proteomics 10:4077–4086

    Article  PubMed  CAS  Google Scholar 

  • Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O’Shea EK (2003) Global analysis of protein localization in budding yeast. Nature 425:686–691

    Article  PubMed  CAS  Google Scholar 

  • Lam YW, Lyon CE, Lamond AI (2002) Large-scale isolation of Cajal bodies from HeLa cells. Mol Biol Cell 13:2461–2473

    Article  PubMed  CAS  Google Scholar 

  • Lam YW, Lamond AI, Mann M, Andersen JS (2007) Analysis of nucleolar protein dynamics reveals the nuclear degradation of ribosomal proteins. Curr Biol 17:749–760

    Article  PubMed  CAS  Google Scholar 

  • Lam YW, Evans VC, Heesom KJ, Lamond AI, Matthews DA (2010) Proteomics analysis of the nucleolus in adenovirus-infected cells. Mol Cell Proteomics 9:117–130

    Article  PubMed  CAS  Google Scholar 

  • Letunic I, Copley RR, Schmidt S, Ciccarelli FD, Doerks T, Schultz J, Ponting CP, Bork P (2004) SMART 4.0: towards genomic data integration. Nucleic Acids Res 32:D142–D144

    Article  PubMed  CAS  Google Scholar 

  • Leung AK, Andersen JS, Mann M, Lamond AI (2003) Bioinformatic analysis of the nucleolus. Biochem J 376:553–569

    Article  PubMed  CAS  Google Scholar 

  • Leung AKL, Trinkle-Mulcahy L, Lam YW, Andersen JS, Mann M, Lamond AI (2006) NOPdb: nucleolar proteome database. Nucleic Acids Res 34:D218–D220

    Article  PubMed  CAS  Google Scholar 

  • Lindstrom MS, Nister M (2010) Silencing of ribosomal protein S9 elicits a multitude of cellular responses inhibiting the growth of cancer cells subsequent to p53 activation. PLoS One 5:e9578

    Article  PubMed  Google Scholar 

  • Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH (2003) Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3:577–587

    Article  PubMed  CAS  Google Scholar 

  • Maggio R (1966) Some properties of isolated nucleoli from guinea-pig liver. Biochim Biophys Acta 119:641–644

    PubMed  CAS  Google Scholar 

  • Masson C, Bouniol C, Fomproix N, Szollosi MS, Debey P, Hernandez-Verdun D (1996) Conditions favoring RNA polymerase I transcription in permeabilized cells. Exp Cell Res 226:114–125

    Article  PubMed  CAS  Google Scholar 

  • Matsuura T, Higashinakagawa T (1992) In vitro transcription in isolated nucleoli of Tetrahymena pyriformis. Dev Genet 13:143–150

    Article  PubMed  CAS  Google Scholar 

  • Mintz PJ, Patterson SD, Neuwald AF, Spahr CS, Spector DL (1999) Purification and biochemical characterization of interchromatin granule clusters. EMBO J 18:4308–4320

    Article  PubMed  CAS  Google Scholar 

  • Mulder NJ, Apweiler R, Attwood TK, Bairoch A, Barrell D, Bateman A, Binns D, Biswas M, Bradley P, Bork P, Bucher P, Copley RR, Courcelle E, Das U, Durbin R, Falquet L, Fleischmann W, Griffiths-Jones S, Haft D, Harte N, Hulo N, Kahn D, Kanapin A, Krestyaninova M, Lopez R, Letunic I, Lonsdale D, Silventoinen V, Orchard SE, Pagni M, Peyruc D, Ponting CP, Selengut JD, Servant F, Sigrist CJA, Vaughan R, Zdobnov EM (2003) The InterPro Database, 2003 brings increased coverage and new features. Nucleic Acids Res 31:315–318

    Article  PubMed  CAS  Google Scholar 

  • Ohashi S, Natsuizaka M, Wong GS, Michaylira CZ, Grugan KD, Stairs DB, Kalabis J, Vega ME, Kalman RA, Nakagawa M, Klein-Szanto AJ, Herlyn M, Diehl JA, Rustgi AK, Nakagawa H (2010) Epidermal growth factor receptor and mutant p53 expand an esophageal cellular ­subpopulation capable of epithelial-to-mesenchymal transition through ZEB transcription ­factors. Cancer Res 70(10):4174–4184

    Article  PubMed  CAS  Google Scholar 

  • Pendle AF, Clark GP, Boon R, Lewandowska D, Lam YW, Andersen J, Mann M, Lamond AI, Brown JW, Shaw PJ (2005) Proteomic analysis of the Arabidopsis nucleolus suggests novel nucleolar functions. Mol Biol Cell 16:260–269

    Article  PubMed  CAS  Google Scholar 

  • Pflieger D, Le Caer JP, Lemaire C, Bernard BA, Dujardin G, Rossier J (2002) Systematic identification of mitochondrial proteins by LC-MS/MS. Anal Chem 74:2400–2406

    Article  PubMed  CAS  Google Scholar 

  • Phair RD, Misteli T (2000) High mobility of proteins in the mammalian cell nucleus. Nature 404:604–609

    Article  PubMed  CAS  Google Scholar 

  • Prives C (1998) Signaling to p53: breaking the MDM2-p53 circuit. Cell 95:5–8

    Article  PubMed  CAS  Google Scholar 

  • Saiga H, Higashinakagawa T (1979) Properties of in vitro transcription by isolated Xenopus oocyte nucleoli. Nucleic Acids Res 6:1929–1940

    Article  PubMed  CAS  Google Scholar 

  • Scherl A, Coute Y, Deon C, Calle A, Kindbeiter K, Sanchez JC, Greco A, Hochstrasser D, Diaz JJ (2002) Functional proteomic analysis of human nucleolus. Mol Biol Cell 13:4100–4109

    Article  PubMed  CAS  Google Scholar 

  • Spector DL, Goldman RD, and Leinw LA (1997) Cells: a laboratory manual, pp. 41.1–41.7, Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Article  PubMed  CAS  Google Scholar 

  • Taylor RS, Wu CC, Hays LG, Eng JK, Yates JR III, Howell KE (2000) Proteomics of rat liver Golgi complex: minor proteins are identified through sequential fractionation. Electrophoresis 21:3441–3459

    Article  PubMed  CAS  Google Scholar 

  • Vandelaer M, Thiry M, Goessens G (1996) Isolation of nucleoli from ELT cells: a quick new method that preserves morphological integrity and high transcriptional activity. Exp Cell Res 228:125–131

    Article  PubMed  CAS  Google Scholar 

  • Voets R, Lagrou A, Hilderson H, Van Dessel G, Dierick W (1979) RNA synthesis in isolated bovine thyroid nuclei and nucleoli. alpha-Amanitin effect, a hint to the existence of a specific regulatory system. Hoppe Seylers Z Physiol Chem 360:1271–1283

    Article  PubMed  CAS  Google Scholar 

  • Volarevic S, Stewart MJ, Ledermann B, Zilberman F, Terracciano L, Montini E, Grompe M, Kozma SC, Thomas G (2000) Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science 288:2045–2047

    Article  PubMed  CAS  Google Scholar 

  • Weserska-Gadek J, Horky M (2003) How the nucleolar sequestration of p53 protein or its interplayers contributes to its (re)-activation. Ann N Y Acad Sci 1010:266–272

    Article  Google Scholar 

  • Yuan X, Zhou Y, Casanova E, Chai M, Kiss E, Grone HJ, Schutz G, Grummt I (2005) Genetic inactivation of the transcription factor TIF-IA leads to nucleolar disruption, cell cycle arrest, and p53-mediated apoptosis. Mol Cell 19:77–87

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Hamanaka RB, Bobrovnikova-Marjon E, Gordan JD, Dai MS, Lu H, Simon MC, Diehl JA (2006) Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest. J Biol Chem 281:30036–30045

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Shi Y, Li X, Du W, Luo G, Gou Y, Wang X, Guo X, Liu J, Ding J, Wu K, Fan D (2010) Inhibition of the p53-MDM2 interaction by adenovirus delivery of ribosomal protein L23 stabilizes p53 and induces cell cycle arrest and apoptosis in gastric cancer. J Gene Med 12:147–156

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, UK

    François-Michel Boisvert & Yasmeen Ahmad

  2. Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, DD15EH, UK

    Angus I. Lamond

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  1. François-Michel Boisvert
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  2. Yasmeen Ahmad
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  3. Angus I. Lamond
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Correspondence to Angus I. Lamond .

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Editors and Affiliations

  1. Dept. Biochemistry, University of Mississippi Medical Center, North State St. 2500, Jackson, 39216, Mississippi, USA

    Mark O. J. Olson

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Boisvert, FM., Ahmad, Y., Lamond, A.I. (2011). The Dynamic Proteome of the Nucleolus. In: Olson, M. (eds) The Nucleolus. Protein Reviews, vol 15. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0514-6_2

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