Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth

Oncogene volume 20, pages 6132–6141 (2001)Cite this article

Abstract

The HMGI proteins (HMGI, HMGY and HMGI-C) have an important role in the chromatin organization and interact with different transcriptional factors. The HMGI genes are expressed at very low levels in normal adult tissues, whereas they are very abundant during embryonic development and in several experimental and human tumours. In order to isolate proteins interacting with the HMGI(Y) proteins, a yeast two-hybrid screening was performed using the HMGI(Y) protein as bait. This analysis led to the isolation of homeodomain-interacting protein kinase-2 (HIPK2), a serine/threonine nuclear kinase. HIPK2 co-immunoprecipitates with the HMGI(Y) protein in 293T cells. The interaction between HIPK2 and HMGI(Y) occurs through the PEST domain of HIPK2 and it is direct because in vitro translated HIPK2 binds HMGI(Y). We also show that HIPK2 is able to phosphorylate the HMGI(Y) protein by an in vitro kinase assay. In order to understand a possible role of HIPK2 gene in cell growth we performed a colony assay which showed an impressive HIPK2 inhibitory effect on normal thyroid cells. Flow cytometric analysis would indicate the block of cell growth at the G2/M phase of the cell cycle. Since normal thyroid cells do not express detectable HMGI(Y) protein levels, we assume that the HIPK2 inhibitory effect is independent from the interaction with the HMGI(Y) protein.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Abe N, Watanabe T, Sugiyama M, Uchimura H, Chiappetta G, Fusco A, Atomi Y . 1999 Cancer Res. 56: 1896–1901

  • Abe N, Watanabe T, Masaki T, Mori T, Sugiyama M, Uchimura H, Fujioka Y, Chiappetta G, Fusco A, Atomi Y . 2000 Cancer Res. 60: 3117–3122

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . 1990 J. Mol. Biol. 215: 403–410

  • Appel RD, Bairoch A, Hochstrasser DF . 1994 Trends Biochem. Sci. 19: 258–260

  • Ashar HR, Schoenberg Fejzo M, Tkachenko A, Zhou X, Fletcher JA, Weremowicz S, Morton CC, Chada K . 1995 Cell 82: 57–65

  • Bandiera A, Bonifacio D, Manfioletti G, Mantovani F, Rustighi A, Zanconati F, Fusco A, Di Bonito L, Giancotti V . 1998 Cancer Res. 58: 426–431

  • Battista S, Fidanza V, Fedele M, Klein-Szanto AJ, Outwater E, Brunner H, Santoro M, Croce CM, Fusco A . 1999 Cancer Res. 59: 4793–4797

  • Baldassarre G, Barone MV, Belletti B, Sandomenico C, Bruni P, Spiezia S, Boccia A, Vento MT, Romano A, Pepe S, Fusco A, Viglietto G . 1999 Oncogene 18: 6241–6251

  • Berlingieri MT, Mantioletti G, Santoro M, Bandiera A, Visconti R, Giancotti V, Fusco A . 1995 Mol. Cell. Biol. 15: 1545–1553

  • Chiappetta G, Bandiera A, Berlingieri MT, Visconti R, Manfioletti G, Battista S, Martinez-Tello FJ, Santoro M, Giancotti V, Fusco A . 1995 Oncogene 10: 1307–1314

  • Chiappetta G, Avantaggiato V, Visconti R, Fedele M, Battista S, Trapasso F, Merciai BM, Fidanza V, Giancotti V, Santoro M, Simeone A, Fusco A . 1996 Oncogene 13: 2439–2446

  • Chiappetta G, Tallini G, De Biasio MC, Manfioletti G, Martines-Tello FJ, Pentimalli F, De Nigris F, Mastro A, Botti G, Fedele M, Bergen N, Santoro M, Giancotti V, Fusco A . 1998 Cancer Res. 58: 4193–4198

  • Chiappetta G, Manfioletti G, Pentimalli F, Abe N, Di Bonito M, Vento MT, Giuliano A, Fedele M, Viglietto G, Santoro M, Watanabe T, Giancotti V, Fusco A . 2001 Int. J. Cancer 91: 147–151

  • Chiariotti L, Benvenuto G, Fedele M, Santoro M, Simeone A, Fusco A, Bruni CB . 1998 Genomics. 47: 258–265

  • Choi YC, Kim YH, Kwon HJ, Kim Y . 1999 J. Biol. Chem. 274: 33194–33197

  • Du W, Maniatis T . 1994 Proc. Natl. Acad. Sci. USA 91: 11318–11322

  • Falvo JV, Thanos D, Maniatis T . 1995 Cell 83: 1101–1111

  • Fashena ST, Reeves R, Ruddle NH . 1992 Mol. Cell. Biol. 12: 894–903

  • Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, Casamassimi A, Santoro M, Giancotti V, Fusco A . 1996 Cancer Res. 56: 1896–1901

  • Fedele M, Benvenuto G, Pero R, Majello B, Battista S, Lembo F, Vollono E, Day PM, Santoro M, Lania L, Bruni CB, Fusco A, Chiariotti L . 2000 J. Biol. Chem. 275: 7894–7901

  • Feinberg AP, Vogelstein B . 1983 Anal. Biochem. 132: 6–13

  • Fusco A, Berlingieri MT, Di Fiore PP, Portella G, Grieco M, Vecchio G . 1987 Mol. Cell. Biol. 7: 3365–3370

  • Giancotti V, Berlingieri MT, Di Fiore PP, Fusco A, Vecchio G, Crane-Robinson C . 1985 Cancer Res. 45: 6051–6057

  • Giancotti V, Pani B, D'Andrea P, Berlingieri MT, Di Fiore PP, Fusco A, Vecchio G, Philip R, Crane-Robinson C, Nicolas RH, Wright CA, Goodwin GH . 1987 EMBO J. 6: 1981–1987

  • Giancotti V, Buratti E, Perissin L, Zorzet S, Balmain A, Portella G, Fusco A, Goodwin GH . 1989 Exp. Cell. Res. 184: 538–545

  • Graham FL, Van der Eb AJ . 1973 Virology 52: 456–467

  • Grosschedl R, Giese K, Pagel J . 1994 Trends Genet. 10: 94–100

  • Hedley ML, Amrein H, Maniatis T . 1995 Proc. Natl. Acad. Sci. USA 92: 11524–11528

  • Johnson KR, Lehn DA, Elton TS, Barr PJ, Reeves R . 1988 J. Biol. Chem. 263: 18338–18342

  • Johnson KR, Lehn DA, Reeves R . 1989 Mol. Cell. Biol. 9: 2114–2123

  • Krishan A . 1975 J. Cell. Biol. 66: 188–193

  • Kim YH, Choi CY, Lee S, Conti MA, Kim Y . 1998 J. Biol. Chem. 273: 25875–25879

  • Kim YH, Choi CY, Kim Y . 1999 Proc. Natl. Acad. Sci. USA 96: 12350–12355

  • Li X, Wang Y, Debatin KM, Hug H . 2000 Biochem. Biophys. Res. Commun. 277: 513–517

  • Lovell-Badge R . 1995 Nature 376: 725–726

  • Manfioletti G, Giancotti V, Bandiera A, Buratti E, Sautiere P, Cary P, Crane-Robinson C, Coles B, Goodwin GH . 1991 Nucleic Acids Res. 19: 6793–6797

  • Motokura T, Keyomarsi K, Kronenberg HM, Arnold A . 1992 J. Biol. Chem. 267: 20412–20415

  • Polyak K, Lee M, Koff A, Roberts JM, Massague J . 1994 Cell 78: 59–66

  • Rochat-Steiner V, Becker K, Micheau O, Schneider P, Burns K, Tschopp J . 2000 J. Exp. Med. 192: 1165–1174

  • Rogers S, Wells R, Rechsteiner M . 1986 Science 234: 3674–3680

  • Sambrook J, Fritsch EF, Maniatis T . 1989 Molecular Cloning, A Laboratory Manual Cold Spring Harbor Laboratory Press

    Google Scholar 

  • Sanger F, Nicklen S, Coulson AR . 1977 Proc. Natl. Acad. Sci. USA 74: 5463–5467

  • Schoenmakers E, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H, Van de Ven WJM . 1995 Nat. Genet. 10: 436–443

  • Tamimi Y, Van Der Poel HG, Denyn MM, Umbas R, Karthaus HFM, Debruyne FMJ, Shalken JA . 1993 Cancer Res. 53: 5512–5516

  • Thanos D, Maniatis T . 1992 Cell 71: 777–789

  • Thanos D, Maniatis T . 1995 Cell 83: 1091–1100

  • Tkachenko A, Ashar HR, Meloni AM, Sandberg AA, Chada KK . 1997 Cancer Res. 57: 2276–2280

  • Vojtek AB, Hollenberg SM . 1995 Methods Enzymol. 255: 331–342

  • Xiao S, Lux ML, Reeves R, Hudson TJ, Fletcher JA . 1997 Am. J. Pathol. 150: 901–910

  • Zhou X, Benson KF, Ashar HR, Chada K . 1995 Nature 376: 771–774

Download references

Acknowledgements

This work has been supported by grants from AIRC (Progetto Speciale Oncosoppressori), the Progetto Finalizzato ‘Biotecnologie’ of the CNR, the MURST projects ‘Terapie antineoplastiche innovative’ and ‘Piani di Potenziamento della Rete Scientifica e Tecnologica’, and from the ‘Ministero della Sanitá’. We thank the Associazione Partenopea per le Ricerche Oncologiche (APRO) for its support. We thank S Gutkind for the pCEFL-HA plasmid. GM Pierantoni is supported by a Fondazione Italiana per la Ricerca sul Cancro (FIRC) fellowship. We are grateful to Jean Gilder for editing the text.

Author information

Authors and Affiliations

  1. Dipartimento di Biologia e Patologia Cellulare e Molecolare, c/o Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli ‘Federico II’, Naples, 80131, Italy

    Giovanna Maria Pierantoni, Monica Fedele, Francesca Pentimalli, Giovanna Benvenuto, Raffaela Pero, Massimo Santoro & Alfredo Fusco

  2. Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, via M. Semmola, Napoli, 80131, Italy

    Giuseppe Viglietto

  3. Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università di Catanzaro, Catanzaro, 88100, Italy

    Lorenzo Chiariotti & Alfredo Fusco

Authors
  1. Giovanna Maria Pierantoni
    View author publications

    Search author on:PubMed Google Scholar

  2. Monica Fedele
    View author publications

    Search author on:PubMed Google Scholar

  3. Francesca Pentimalli
    View author publications

    Search author on:PubMed Google Scholar

  4. Giovanna Benvenuto
    View author publications

    Search author on:PubMed Google Scholar

  5. Raffaela Pero
    View author publications

    Search author on:PubMed Google Scholar

  6. Giuseppe Viglietto
    View author publications

    Search author on:PubMed Google Scholar

  7. Massimo Santoro
    View author publications

    Search author on:PubMed Google Scholar

  8. Lorenzo Chiariotti
    View author publications

    Search author on:PubMed Google Scholar

  9. Alfredo Fusco
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Alfredo Fusco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pierantoni, G., Fedele, M., Pentimalli, F. et al. High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth. Oncogene 20, 6132–6141 (2001). https://doi.org/10.1038/sj.onc.1204635

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1204635

Keywords

This article is cited by

Search

Advanced search

Quick links