Skip to main content
SpringerLink
Log in

Nucleophosmin/B23: A Multifunctional Regulator that Determines the Fate of CCN2 mRNA

  • Chapter
  • First Online:
CCN Proteins in Health and Disease

Abstract

CCN2/CTGF is a multifunctional molecule that has been shown to play a central role in chondrocyte differentiation. During this process, the expression of ccn2 is tightly regulated to confer a maximal level at prehypertrophic – hypertrophic stages, in which the 3'-untranslated region (UTR) of the mRNA is critically involved in mediating its post-transcriptional regulation. In our previous studies, we found that a 40-kDa protein binding specifically to an RNA cis-element, 3'-100/50, in the 3'-UTR of the chicken ccn2 mRNA regulated the intracellular stability of the mRNA. The interaction of this 40-kDa protein with 3′-100/50 was enhanced in proliferating chondrocytes, in which ccn2 mRNA is rapidly degraded; whereas a prolonged half life of ccn2 mRNA is observed in hypertrophic chondrocytes, where the interaction of the 40 kDa-protein and 3'-100/50 is diminished. Collectively, the data suggested that this 40-kDa protein acts as a ccn2-specific mRNA destabilizer during chondrocyte differentiation.

In this present study we finally identified this 40-kDa protein as nucleophosmin (NPM)/B23. NPM is a nuclear-cytoplasmic shuttling protein that is characterized by its multiple functionality. This protein is known to be a histone chaperone, a regulator of ribosomal RNA transcription, as well as an RNA-binding post-transcriptional regulator of gene expression. In our hands, direct binding of NPM to 3'-100/50 was confirmed not only by RNA EMSA and UV crosslinking assays, but also by RNA immunoprecipitation analysis. By using recombinant chicken NPM, we could successfully reconstitute the post-transcriptional regulation of ccn2 by NPM in vitro and found that this regulation was more robust in chondrocytes than in fibroblasts. Furthermore, siRNA-mediated gene silencing of NPM in vivo clearly showed enhanced ccn2 gene expression and a prolonged half life of the ccn2 mRNA, confirming the functional property of NPM as a specific destabilizer of the ccn2 mRNA in living cells.

The 5'-100/50 element, a target of NPM, is evolutionally conserved among vertebrate species. Therefore, we consider NPM to be a critical post-transcriptional regulator of ccn2 acting via 3'-UTR during endochondral ossification and possibly, in other physiological and pathological states as well.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

NPM:

nucleophosmin

EMSA:

electromobility-shift assay

UTR:

untranslated region

CEF:

chicken embryonic fibroblast

US:

upper sternum

LS:

lower sternum

IVDA:

in vitro degradation assay

References

  • Asano M., Kubota S., Nakanishi T., Nishida T., Yamaai T., Yosimichi G., Ohyama K., Sugimoto T., Murayama Y., Takigawa M. (2005). Effect of connective tissue growth factor (CCN2/CTGF) on proliferation and differentiation of mouse periodontal ligament-derived cells. Cell Commun Signal 3: 11.

    Google Scholar 

  • Babic A.M., Chen C.C., Lau L.F. (1999). Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo. Mol Cell Biol 19: 2958–2966.

    PubMed  CAS  Google Scholar 

  • Bartel D.P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136: 215–233.

    Article  PubMed  CAS  Google Scholar 

  • Borer R.A., Lehner C.F., Eppenberger H.M., Nigg E.A. (1989). Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell 56: 379–390.

    Article  PubMed  CAS  Google Scholar 

  • Bradham D.M., Igarashi A., Potter R.L., Grotendorst G.R. (1991). Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol 114: 1285–1294.

    Article  CAS  Google Scholar 

  • Brigstock, D.R. 1999. The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family. Endocr. Rev. 20: 189–206.

    CAS  Google Scholar 

  • Chan P.K., Aldrich M., Cook R.G., Busch H. (1986a). Amino acid sequence of protein B23 phosphorylation site. J Biol Chem 261: 1868–1872.

    PubMed  CAS  Google Scholar 

  • Colombo E., Marine J.C., Danovi D., Falini B., Pelicci P.G. (2002). Nucleophosmin regulates the stability and transcriptional activity of p53. Nat Cell Biol 4: 529–533.

    Article  PubMed  CAS  Google Scholar 

  • Döhner K., Schlenk R.F., Habdank M., Scholl C., Rücker F.G., Corbacioglu A., Bullinger L., Fröhling S., Döhner H. (2005). Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 106: 3740–3746.

    Article  PubMed  CAS  Google Scholar 

  • Eguchi T., Kubota S., Kondo S., Kuboki T., Yatani H., Takigawa M. (2002). A novel cis-element that enhances connective tissue growth factor gene expression in chondrocytic cells. Biochem Biophys Res Commun 295: 445–451.

    Article  PubMed  CAS  Google Scholar 

  • Eguchi T., Kubota S., Kawata K., Mukudai Y., Ohgawara T., Miyazono K., Nakao K., Kondo S., Takigawa M. (2007). Different transcriptional strategies for ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines. Biochimie 89: 278–288.

    Article  PubMed  CAS  Google Scholar 

  • Eguchi T., Kubota S., Kawata K., Mukudai Y., Uehara J., Ohgawara T., Ibaragi S., Sasaki S., Kuboki T., Takigawa M. (2008). Novel transcription factor-like function of human MMP3 regulating CTGF/CCN2 gene. Mol Cell Biol 28: 2391–2413.

    Article  PubMed  CAS  Google Scholar 

  • Enomoto T., Lindström M.S., Jin A., Ke H., Zhang Y. (2006). Essential role of the B23/NPM core domain in regulating ARF binding and B23 stability. J Biol Chem 281: 18463–18472.

    Article  PubMed  CAS  Google Scholar 

  • Falini B., Mecucci C., Tiacci E., Alcalay M., Rosati R., Pasqualucci L., La Starza R., Diverio D., Colombo E., Santucci A., Bigerna B., Pacini R., Pucciarini A., Liso A., Vignetti M., Fazi P., Meani N., Pettirossi V., Saglio G., Mandelli F., Lo-Coco F., Pelicci P.G., Martelli M.F., GIMEMA Acute Leukemia Working Party. (2005). Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352: 254–266.

    Article  PubMed  CAS  Google Scholar 

  • Fankhauser C., Izaurralde E., Adachi Y., Wingfield P., Laemmli U.K. (1991). Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element. Mol Cell Biol 11: 2567–2575.

    PubMed  CAS  Google Scholar 

  • Feuerstein N., Chan P.K., Mond J.J. (1988). Identification of numatrin, the nuclear matrix protein associated with induction of mitogenesis, as the nucleolar protein B23. Implication for the role of the nucleolus in early transduction of mitogenic signals. J Biol Chem 263: 10608–10612.

    PubMed  CAS  Google Scholar 

  • Frazier K., Williams S., Kothapalli D., Klapper H., Grotendorst G.R. (1996). Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol 107: 404–411.

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto G., Inoki I., Fujii Y., Aoki T., Ikeda E., Okada Y. (2002). Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. J Biol Chem 277: 36288–36295.

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto Y., Shindo-Okada N., Tani M., Nagamachi Y., Takeuchi K., Shiroishi T., Toma H., Yokota J. (1998). Expression of the Elm1 gene, a novel gene of the CCN (connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses in vivo tumor growth and metastasis of K-1735 murine melanoma cells. J Exp Med 187: 289–296.

    Article  PubMed  CAS  Google Scholar 

  • Herrera J.E., Savkur R., Olson M.O. (1995). The ribonuclease activity of nucleolar protein B23, Nucleic Acids Res 23: 3974–3979.

    CAS  Google Scholar 

  • Hingorani K., Szebeni A., Olson M.O. (2000). Mapping the functional domains of nucleolar protein B23. J Biol Chem 275: 24451–24457.

    Article  PubMed  CAS  Google Scholar 

  • Inouye C.J., Seto E. (1994). Relief of YY1-induced transcriptional repression by protein-protein interaction with the nucleolar phosphoprotein B23. J Biol Chem 269: 6506–6510.

    PubMed  CAS  Google Scholar 

  • Joliot V., Martinerie C., Dambrine G., Plassiart G., Brisac M., Crochet J., Perbal B. (1992). Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. Mol Cell Biol 12: 10–21.

    PubMed  CAS  Google Scholar 

  • Kikuchi K., Kadono T., Ihn H., Sato S., Igarashi A., Nakagawa H., Tamaki K., Takehara K. (1995). Growth regulation in scleroderma fibroblasts: increased response to transforming growth factor-beta 1. J Invest Dermatol 105: 128–132.

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi T., Kubota S., Asaumi K., Kawaki H., Nishida K., Kawata T., Mitani S., Tabata Y., Ozaki T., Takigawa M. (2008). Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel. Tissue Eng Part A 14: 1089–1098.

    Article  PubMed  CAS  Google Scholar 

  • Kondo S., Kubota S., Eguchi T., Hattori T., Nakanishi T., Sugahara T., Takigawa M. (2000). Characterization of a mouse ctgf 3'-UTR segment that mediates repressive regulation of gene expression. Biochem Biophys Res Commun 278: 119–124.

    Article  PubMed  CAS  Google Scholar 

  • Kondo S., Kubota S., Mukudai Y., Moritani N., Nishida T., Matsushita H., Matsumoto S., Sugahara T., Takigawa M. (2006). Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3'-untranslated region interacting with a cellular protein in human chondrosarcoma cells. Oncogene 25: 1099–1110.

    Article  PubMed  CAS  Google Scholar 

  • Kondo T., Minamino N., Nagamura-Inoue T., Matsumoto M., Taniguchi T., Tanaka N. (1997). Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity. Oncogene 15: 1275–1281.

    Article  PubMed  CAS  Google Scholar 

  • Kothapalli D., Frazier K.S., Welply A., Segarini P.R., Grotendorst G.R. (1997). Transforming growth factor beta induces anchorage-independent growth of NRK fibroblasts via a connective tissue growth factor-dependent signaling pathway. Cell Growth Differ 8: 61–68.

    PubMed  CAS  Google Scholar 

  • Kubota S., Eguchi T., Shimo T., Nishida T., Hattori T., Kondo S., Nakanishi T., Takigawa M. (2001). Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells. Bone 29: 155–161.

    Article  PubMed  CAS  Google Scholar 

  • Kubota S., Hattori T, Nakanishi T., Takigawa M. (1999). Involvement of cis-acting repressive element(s) in the 3'-untranslated region of human connective tissue growth factor gene. FEBS Lett 450: 84–88.

    Article  PubMed  CAS  Google Scholar 

  • Kubota S., Kondo S., Eguchi T., Hattori T., Nakanishi T., Pomerantz R.J., Takigawa M. (2000). Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: similarities to retroviral RNA-protein interactions. Oncogene 19: 4773–4786.

    Article  PubMed  CAS  Google Scholar 

  • Kubota S., Mukudai Y., Moritani N.H., Nakao K., Kawata K., Takigawa M. (2005). Translational repression by the cis-acting element of structure-anchored repression (CAESAR) of human ctgf/ccn2 mRNA. FEBS Lett 579: 3751–3758.

    Article  PubMed  CAS  Google Scholar 

  • Kubota S., Takigawa M. (2007a). CCN family proteins and angiogenesis: from embryo to adulthood, Angiogenesis 10: 1–11.

    CAS  Google Scholar 

  • Kubota S., Takigawa M. (2007b). Role of CCN2/CTGF/Hcs24 in bone growth. Int Rev Cytol 257: 1–41.

    Article  PubMed  CAS  Google Scholar 

  • Lau L.F., Nathans D. (1985). Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells. EMBO J 4: 3145–3151.

    PubMed  CAS  Google Scholar 

  • Lau L.F., Lam S.C. (1999). The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res 248: 44–57.

    Article  PubMed  CAS  Google Scholar 

  • Leask A., Holmes A., Black C.M., Abraham D.J. (2003). Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem 278: 13008–13015.

    Article  PubMed  CAS  Google Scholar 

  • Maridor G., Nigg E.A. (1990). cDNA sequences of chicken nucleolin/C23 and NO38/B23, two major nucleolar proteins. Nucleic Acids Res 18: 1286.

    Article  PubMed  CAS  Google Scholar 

  • Merritt C., Rasoloson D., Ko D., Seydoux G. (2008). 3' UTRs are the primary regulators of gene expression in the C. elegans germline. Curr Biol 18: 1476–1482.

    Article  PubMed  CAS  Google Scholar 

  • Mukudai Y., Kubota S., Takigawa M. (2003). Conserved repressive regulation of connective tissue growth factor/hypertrophic chondrocyte-specific gene 24 (ctgf/hcs24) enabled by different elements and factors among vertebrate species. Biol Chem 381: 1–9.

    Article  Google Scholar 

  • Mukudai Y., Kubota S., Eguchi T., Kondo S., Nakao K., Takigawa M. (2005). Regulation of chicken ccn2 gene by interaction between RNA cis-element and putative trans-factor during differentiation of chondrocytes. J Biol Chem 280: 3166–3177.

    Article  PubMed  CAS  Google Scholar 

  • Mukudai Y., Kubota S., Kawaki H., Kondo S., Eguchi T., Sumiyoshi K., Ohgawara T., Shimo T., Takigawa M. (2008). Post-transcriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation. Mol Cell Biol 28: 6134–6147.

    Article  PubMed  CAS  Google Scholar 

  • Murano K., Okuwaki M., Hisaoka M., Nagata K. (2008). Transcription regulation of the rRNA gene by a multifunctional nucleolar protein, B23/nucleophosmin, through its histone chaperone activity. Mol Cell Biol 28: 3114–3126.

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi T., Kimura Y., Tamura T., Ichikawa H., Yamaai Y., Sugimoto T., Takigawa M. (1997). Cloning of a mRNA preferentially expressed in chondrocytes by differential display-PCR from a human chondrocytic cell line that is identical with connective tissue growth factor (CTGF) mRNA. Biochem Biophys Res Commun 234: 206–210.

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi T., Nishida T., Shimo T., Kobayashi K., Kubo T., Tamatani T., Tezuka K., Takigawa M. (2000). Effects of CTGF/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture. Endocrinology 141: 264–273.

    Article  PubMed  CAS  Google Scholar 

  • Nishida T., Nakanishi T., Asano M., Shimo T., Takigawa M. (2000). Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro. J Cell Physiol 184: 197–206.

    Article  PubMed  CAS  Google Scholar 

  • Nishida T., Kubota S., Nakanishi T., Kuboki T., Yosimichi G., Kondo S., Takigawa M. (2002). CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes. J Cell Physiol 192: 55–63.

    Article  PubMed  CAS  Google Scholar 

  • Nishida T., Kubota S., Kojima S., Kuboki T., Nakao K., Kushibiki T., Tabata Y., Takigawa M. (2004). Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor). J Bone Miner Res 19: 1308–1319.

    Article  PubMed  CAS  Google Scholar 

  • Ohgawara T., Kubota S., Kawaki H., Kondo S., Eguchi T., Kurio N., Aoyama E., Sasaki A., Takigawa M. (2009). Regulation of chondrocytic phenotype by micro RNA 18a: involvement of Ccn2/Ctgf as a major target gene. FEBS Lett 583: 1006–1010.

    Google Scholar 

  • Okuda M., Horn H.F., Tarapore P., Tokuyama Y., Smulian A.G., Chan P.K., Knudsen E.S., Hofmann I.A., Snyder J.D., Bove K.E., Fukasawa K. (2000). Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell 103: 127–140.

    Article  PubMed  CAS  Google Scholar 

  • Ono M., Kubota S., Fujisawa T., Sonoyama W., Kawaki H., Akiyama K., Oshima M., Nishida T., Yoshida Y., Suzuki K., Takigawa M., Kuboki T. (2008). Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2. Cell Transplant 17: 231–240.

    Article  PubMed  Google Scholar 

  • Orrick L.R., Olson M.O., Busch H. (1973). Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 70: 1316–1320.

    Article  PubMed  CAS  Google Scholar 

  • Parker R., U. Sheth. (2007). P bodies and the control of mRNA translation and degradation. Mol Cell 25: 635–646.

    Article  PubMed  CAS  Google Scholar 

  • Pennica D., Swanson T.A., Welsh J W., Roy M.A., Lawrence D.A., Lee J., Brush J., Taneyhill L.A., Deuel B., Lew M., Watanabe C., Cohen R.L., Melhem M.F., Finley G.G., Quirke P., Goddard A.D., Hillan K.J., Gurney A.L., Botstein D., Levine A.J. (1998). WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc Natl Acad Sci USA 95: 14717–14722.

    Article  PubMed  CAS  Google Scholar 

  • Perbal B. (2004). CCN proteins: multifunctional signalling regulators. Lancet 363: 62–64.

    Article  PubMed  CAS  Google Scholar 

  • Perbal B., Takigawa M. (ed.) (2005). CCN proteins – a new family of cell growth and differentiation regulators. Imperial College Press, London, UK, pp 1–311.

    Google Scholar 

  • Prestayko A.W., Klomp G.R., Schmoll D.J., Busch H. (1974). Comparison of proteins of ribosomal subunits and nucleolar preribosomal particles from Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Biochemistry 13: 1945–1951.

    Article  PubMed  CAS  Google Scholar 

  • Ryseck R.P., Macdonald-Bravo H., Mattei M.G., Bravo R. (1991). Structure, mapping, and expression of fisp-12, a growth factor-inducible gene encoding a secreted cysteine-rich protein. Cell Growth Differ 2: 225–233.

    PubMed  CAS  Google Scholar 

  • Savkur R.S., Olson M.O. (1998). Preferential cleavage in pre-ribosomal RNA by protein B23 endoribonuclease. Nucleic Acids Res 26: 4508–4515.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt-Zachmann M.S., Hugle-Dorr B., Franke W.W. (1987). A constitutive nucleolar protein identified as a member of the nucleoplasmin family. EMBO J 6: 1881–1890.

    PubMed  CAS  Google Scholar 

  • Sela-Brown A., Silver J., Brewer G., Naveh-Many T. (2000). Identification of AUF1 as a parathyroid hormone mRNA 3'-untranslated region-binding protein that determines parathyroid hormone mRNA stability. J Biol Chem 275: 7424–7429.

    Article  PubMed  CAS  Google Scholar 

  • Shimo T., Nakanishi T., Nishida T., Asano M., Kanyama M., Kuboki T., Tamatani T., Tezuka K., Takemura M., Matsumura T., Takigawa M. (1999). Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo. J Biochem (Tokyo) 126: 137–145.

    CAS  Google Scholar 

  • Takigawa M., Tajima K., Pan H.O., Enomoto M., Kinoshita A., Suzuki F., Takano Y., Mori Y. (1989). Establishment of a clonal human chondrosarcoma cell line with cartilage phenotypes. Cancer Res 49: 3996–4002.

    PubMed  CAS  Google Scholar 

  • Takigawa M., Nakanishi T., Kubota S., Nishida T. (2003). Role of CTGF/HCS24/ecogenin in skeletal growth control. J Cell Physiol 194: 256–266.

    Article  PubMed  CAS  Google Scholar 

  • Wang D., Baumann A., Szebeni A., Olson M.O. (1994). The nucleic acid binding activity of nucleolar protein B23.1 resides in its carboxyl-terminal end. J Biol Chem 269: 30994–30998.

    PubMed  CAS  Google Scholar 

  • Yang C., Maiguel D.A., Carrier F. (2002). Identification of nucleolin and nucleophosmin as genotoxic stress-responsive RNA-binding proteins. Nucleic Acids Res 30: 2251–2260.

    Article  PubMed  CAS  Google Scholar 

  • Yung B.Y., Busch H., Chan P.K. (1986). Effects of luzopeptins on protein B23 translocation and ribosomal RNA synthesis in HeLa cells. Cancer Res 46: 922–925.

    PubMed  CAS  Google Scholar 

  • Zhang R., Averboukh L., Zhu W., Zhang H., Jo H., Dempsey P.J., Coffey R.J., Pardee A.B., Liang P. (1998). Identification of rCop-1, a new member of the CCN protein family, as a negative regulator for cell transformation. Mol Cell Biol 18: 6131–6141.

    PubMed  CAS  Google Scholar 

  • Zirwes R.F., Kouzmenko A.P., Peters J.M., Franke W.W., Schmidt-Zachmann M.S. (1997). Topogenesis of a nucleolar protein: determination of molecular segments directing nucleolar association. Mol Biol Cell 8: 231–248.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the programs Grants-in-aid for Scientific Research (S) [to M.T.] and (C) [to S.K.], and Support Program for Improving Graduate School Education (C014) [to K.S. and T.O] from Japan Society for the Promotion of Science. We thank Drs. Eriko Aoyama, Takashi Nishida, and Takako Hattori for their helpful suggestions.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho Kita-ku, Okayama, 700-8525, Japan

    Satoshi Kubota & Masaharu Takigawa

  2. Bio-Dental Research Center, Okayama University, Okayama, Japan

    Yoshiki Mukudai

  3. Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan

    Harumi Kawaki, Seiji Kondo & Kumi Sumiyoshi

  4. Department of Oral Disease Research, National Institute of Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Japan

    Takanori Eguchi

  5. Department of Biochemistry & Molecular Dentistry, Okayama University, Okayama, Japan

    Takanori Eguchi & Toshihiro Ohgawara

  6. Department of Oral & Maxillofacial Rehabilitation, Okayama University, Okayama, Japan

    Toshihiro Ohgawara

  7. Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Tsuyoshi Shimo

Authors
  1. Satoshi Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshiki Mukudai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harumi Kawaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seiji Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takanori Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kumi Sumiyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshihiro Ohgawara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tsuyoshi Shimo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masaharu Takigawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Satoshi Kubota or Masaharu Takigawa .

Editor information

Editors and Affiliations

  1. Med Sci-I 6447, Ann Arbor, 48109, USA

    Annick Perbal

  2. Shikata-Cho 2-5-1, Okayama, 700-8525, Japan

    Masaharu Takigawa

  3. Palais du Grand Large, International CCN Society, Saint-Malo, France

    Bernard Perbal

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Kubota, S. et al. (2010). Nucleophosmin/B23: A Multifunctional Regulator that Determines the Fate of CCN2 mRNA. In: Perbal, A., Takigawa, M., Perbal, B. (eds) CCN Proteins in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3779-4_4

Download citation

Publish with us

Policies and ethics

Search

Navigation