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:

Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target

Oncogene volume 22, pages 8738–8748 (2003)Cite this article

Abstract

The discovery of the p73 and p63 genes, homologous to p53 tumor suppressor has uncovered a family of transcription factors and widened the scenario of cell cycle control and apoptosis. We have identified a putative p53-responsive element in the human adenosine deaminase (ADA) gene, an important enzyme involved in nucleotide metabolism, the deficit of which causes the inhibition of DNA synthesis and repair. Here, we demonstrate that the ectopic expression of p73 isoforms leads to the ADA gene upregulation, showing for the first time a correlation between p73 and ADA. We found that p73 promotes ADA gene expression following a dNTP unbalance generated by ADA enzyme deficiency and 2′deoxyadenosine accumulation. The abrogation of p73 transcriptional activity by the specific dominant-negative p73DD abolishes ADA induction. By contrast, the ADA gene does not appear to be a functional p53 target in the physiological conditions we tested. On the whole, our results contribute to the emerging picture that p73 could play a different role from p53 in normal growth and development by inducing alternative target genes, which are not shared by p53.

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

Access options

Buy this article

  • Purchase on Springer Link
  • 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
Figure 7
Figure 8

Similar content being viewed by others

References

  • Aronow BJ, Silbiger RN, Dusing MR, Stock JL, Yager KL, Potter SS, Hutton JJ and Wiginton DA . (1992). Mol. Cell. Biol., 12, 4170–4185.

  • Balint E, Phillips AC, Kozlov S, Stewart CL and Vousden KH . (2002). Proc. Natl. Acad. Sci. USA, 99, 3529–3534.

  • Bemi V, Tazzini N, Banditelli S, Giorgelli F, Pesi R, Turchi G, Mattana A, Sgarrella F, Tozzi MG and Camici M . (1998). Int. J. Cancer, 75, 713–720.

  • Benveniste P and Cohen A . (1995). Proc. Natl. Acad. Sci. USA, 92, 8373–8377.

  • Bian J, Jacobs C, Wang Y and Sun Y . (1996). Carcinogenesis, 17, 2559–2562.

  • Blackburn MR, Wakamiyaa M, Caskey CT and Kellems RE . (1995). J. Biol. Chem., 270, 23891–23894.

  • Bourdon JC, Deguin-Chambon V, Lelong JC, Dessen P, May P, Debuire B and May E . (1997). Oncogene, 14, 85–94.

  • Camici M, Turriani M, Tozzi MG, Turchi G, Cos J, Alemany C, Miralles A, Noe and Ciudad C . (1995). Int. J. Cancer, 62, 176–183.

  • Chinsky JM, Maa MC, Ramamurthy V and Kellems RE . (1989). J. Biol. Chem., 264, 14561–14565.

  • Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R and Campioni E . (2001). Med. Res. Rev., 21, 105–128.

  • D'Erchia AM, Tullo A, Pesole G, Saccone C and Sbisà E . (2003). Curr. Genom., 4, 13–26.

  • Di Como CJ, Gaiddon C and Prives C . (1999). Mol. Cell. Biol., 19, 1438–1449.

  • Duriez C, Falette N, Cortes U, Moyret-Lalle C and Puisieux A . (2000). Oncogene, 19, 2461–2464.

  • Dusing MR and Wiginton DA . (1994). Nucleic Acids Res., 22, 669–677.

  • Dusing MR, Brickner AG, Thomas MB and Wiginton DA . (1997). J. Biol. Chem., 272, 26634–26642.

  • El Deiry WS, Kern SE, Pietenpol JA, Kinzler KW and Vogelstein B . (1992). Nat. Genet., 1, 45–49.

  • Fontemaggi G, Kela I, Amariglio N, Rechavi G, Krishnamurthy J, Strano S, Sacchi A, Givol D and Blandino G . (2002). J. Biol. Chem., 277, 43359–43368.

  • Giblett ER, Anderson JE, Cohen F, Pollara B and Meuwissen HJ . (1972). Lancet, II, 1067–1069.

  • Hansen R and Oren M . (1997). Curr. Opin. Genet. Dev., 7, 46–51.

  • He Y, Chu SH and Walker WA . (1993). J. Nutr., 123, 1017–1027.

  • Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH and Kaelin Jr WG . (2000). Nature, 407, 645–648.

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscam JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F and Caput D . (1997). Cell, 90, 809–819.

  • Kizaki H, Shimada H, Ohsaka F and Sakurada T . (1988). J. Immunol., 141, 1652–1657.

  • Ko LJ and Prives C . (1996). Genes Dev., 10, 1054–1072.

  • Levine AJ . (1997). Cell, 88, 323–331.

  • Levrero M, De Laurenzi V, Costanzo A, Sabatini S, Gong J, Wang JYJ and Melino G . (2000). J. Cell Sci., 113, 1661–1670.

  • Lissy NA, Davis PK, Irwin M, Kaelin WG and Dowdy SF . (2000). Nature, 407, 642–645.

  • Lohrum MAE and Vousden KH . (2000). Trends Cell Biol., 10, 197–202.

  • Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR and Bradley A . (1999). Nature, 398, 708–713.

  • Moriwaki Y, Yamamoto T and Higashino K . (1999). Histol. Histopathol., 14, 1321–1340.

  • Nagaich AK, Appella E and Harrington RE . (1997). J Biol. Chem., 23, 14842–14849.

  • Saccone C, Barome PO, D'Erchia AM, D'Errico I, Pesole G, Sbisà and Tullo A . (2002). Gene, 300, 195–201.

  • Sasaki Y, Ishida S, Morimoto I, Yamashita T, Kojima T, Kihara C, Tanaka T, Imai K, Nakamura Y and Tokino T . (2002). J. Biol. Chem., 277, 719–724.

  • Sciacchitano S, Orecchio A, Lavra L, Misti S, Giacchini A, Zani M, Danese D, Gurtner A, Soddu S, Di Mario U and Andreoli M . (2002). Mol. Endocrinl., 16, 1577–1589.

  • Shi D, Winston JH, Blackburn MR, Datta SK, Hanten G and Kellems RE . (1997). J. Biol. Chem., 272, 2334–2341.

  • Steegenga WT, Shvarts A, Riteco N, Bos JL and Jochemsen AG . (1999). Mol. Cell. Biol., 19, 3885–3894.

  • Ueda Y, Hijikata M, Takagi S, Takada R, Takada S, Chiba T and Shimotohno K . (2001). Biochem. Biophys. Res. Commun., 283, 327–333.

  • Vikhanskaya F, D'Incalci M and Broggini M . (2000). Nucleic Acids Res., 28, 513–519.

  • Vikhanskaya F, Marchini S, Marabese M, Galliera E and Broggini M . (2001). Cancer Res., 61, 935–938.

  • Vogelstein B, Lane D and Levine AJ . (2000). Nature, 408, 307–310.

  • Wakade AR, Przywara DA, Palmer KC, Kulkarni JS and Wakade TD . (1995). J. Biol. Chem., 270, 17986–17992.

  • Werner H, Karnieli E, Rauscher FJ and LeRoith D . (1996). Proc. Natl. Acad. Sci. USA, 93, 8318–8323.

  • Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C and McKeon F . (1999). Nature, 398, 714–718.

  • Yang A, Kaghad M, Wang Y, Gillet E, Fleming MD, Dotsch V, Andrews NC, Capu D and McKeon F . (1998). Cell, 2, 305–316.

  • Yang A and McKeon F . (2000). Nat. Rev. Mol Cell. Biol., 1, 199–207.

  • Yang A, Kaghad M, Caput D and McKeon F . (2002). Trends Genet., 18, 90–95.

  • Yang A, Walker N, Bronson RT, Kaghad M, Oosterwegel M, Bonnin J, Vagner C, Bonnet H, Dikkes P and Sharpe A et al. (2000). Nature, 404, 99–103.

  • Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW and Vogelstein B . (1999). Proc. Natl. Acad. Sci. USA, 96, 14517–14522.

  • Zeng X, Li X, Miller A, Yuan Z, Yuan W, Kwok RPS, Goodman R and Lu H . (2000). Mol. Cell. Biol., 20, 1299–1310.

  • Zheng X and Chen X . (2001). FEBS Lett., 489, 4–7.

  • Zhou H, Zhang Y, Ou-Yang Z, Lindsay SM, Feng XZ, Balagurumoorthy P and Harrington RE . (2001). J. Mol. Biol., 306, 227–238.

Download references

Acknowledgements

The A2780/pcDNA3 and A2780/p73α.4 clones cell lines were kindly provided by Dr Massimo Broggini of the ‘Mario Negri’ Institute, Milan. The H1299-p53-tet cell line was kindly provided by Professor David Lane of the University of Dundee. The recombinant plasmids pcDNA3 p73α and p73β were kindly provided by Dr G Melino of the IDI-IRCCS Biochemistry Lab., c/o University Tor Vergata, Rome. We wish to thank Dr Vincenzo De Salvo and Dr Fortunato Morabito of the Centro Trapianti Midollo Osseo e Terapie Emato-Oncologiche Sovramassimali ‘Alberto Neri’ (Reggio Calabria) for providing 2′-deoxycoformycin (dCF). We wish to thank Dr Farizio Loiacono, Dr Konstantinos Lefkimmiatis and Dr Rosalia Marzella for their help. We wish to acknowledge Dr Aurelio Reyes and D'Erchia Anna Maria for critical discussion. This work was supported by grants from the Italian Association for Cancer Research (AIRC) and by MURST Ingegneria Molecolare Cluster C03 Legge 488/92. MG was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC).

Author information

Authors and Affiliations

  1. Istituto di Tecnologie Biomediche, Sezione di Bari di Bioinformatica e Genomica CNR, Via Amendola, 165/A, Bari, 70126, Italy

    Apollonia Tullo, Paola Centonze, Cecilia Saccone & Elisabetta Sbisà

  2. Dipartimento di Biochimica e Biologia Molecolare, Universita' degli Studi di Bari, Via Orabona, 4, Bari, 70125, Italy

    Giuseppe Mastropasqua & Cecilia Saccone

  3. Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School University of Dundee, Dundee, DD1 9SY, UK

    Jean Christophe Bourdon

  4. Laboratorio Nazionale, Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, Trieste, Italy

    Monica Gostissa & Giannino Del Sal

  5. Laboratory of Gene Expression, Fondazione Andrea Cesalpino, University of Rome La Sapienza, Rome, Italy

    Antonio Costanzo & Massimo Levrero

  6. Department of Dermatology, University of Rome Tor Vergata, Rome, 00161, Italy

    Antonio Costanzo

  7. Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Universita' degli Studi di Trieste, Via L. Giorgeri 1, Trieste, 34100, Italy

    Giannino Del Sal

Authors
  1. Apollonia Tullo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Mastropasqua
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean Christophe Bourdon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paola Centonze
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Monica Gostissa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Costanzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Massimo Levrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giannino Del Sal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Cecilia Saccone
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Elisabetta Sbisà
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Apollonia Tullo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tullo, A., Mastropasqua, G., Bourdon, J. et al. Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target. Oncogene 22, 8738–8748 (2003). https://doi.org/10.1038/sj.onc.1206967

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206967

Keywords

This article is cited by

Search

Advanced search

Quick links