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Delineation of the domains required for physical and functional interaction of p14ARF with human topoisomerase I

Oncogene volume 22, pages 1945–1954 (2003)Cite this article

An Erratum to this article was published on 04 May 2006

Abstract

We recently reported an interaction between the p14ARF protein and human topoisomerase I (Topo I) resulting in the stimulation of the relaxation activity of Topo I. Our data showed that the complex between the two proteins was located within the nucleolus. In the present work, we have investigated the regions of p14ARF involved in this interaction by using targeted point mutagenesis and deletion mutants. A region encompassing exon 2-encoded sequence was required for physical binding of p14ARF to Topo I as well as for stimulatory activity of the enzyme. Exon 1β-encoded segment was not implicated in the interaction. Moreover, among p14ARF point mutants selected for their high conservation among different mammalian species, mutant p14ARF (RR87, 88AA) did not stimulate Topo I in spite of its association with the enzyme, suggesting its direct implication in the functional activity of ARF. In contrast, one mutant, p14ARF (R71A), was more efficient than wild-type protein to activate Topo I, suggesting that this residue is a key element to modulate Topo I activity. Finally, only ARF–Topo I complexes containing p14ARF exon 2 segment were found to be localized in the nucleolus, suggesting that this subnuclear location is linked to the biological function of the ARF–Topo I complex.

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References

  • Carnero A, Hudson JD, Price CM and Beach DH . (2000). Nat. Cell Biol., 2, 148–154.

  • Della Valle V, Duro D, Bernard O and Larsen CJ . (1997). Oncogene, 15, 2475–2481.

  • Gazzeri S, Della Valle V, Chaussade L, Brambilla C, Larsen CJ and Brambilla E . (1998). Cancer Res. 58, 3926–3931.

  • Guldner HH, Szostecki C, Vosberg HP, Lakomek HJ, Penner E and Bautz FA . (1986). Chromosoma, 94, 132–138.

  • Hahn WC and Weinberg RA . (2002). Nat. Rev. Cancer, 2, 331–341.

  • Higuchi R, Krummel B and Saiki RK . (1988). Nucleic Acids Res., 16, 7351–7367.

  • Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G and Sherr CJ . (1997). Cell, 91, 649–659.

  • Karayan L, Riou JF, Séité P, Migeon J, Cantereau A and Larsen CJ . (2001). Oncogene, 20, 836–848.

  • Kubbutat MH, Jones SN and Vousden KH . (1997). Nature, 6630, 299–303.

  • Kurokawa K, Tanaka T and Kato J . (1999). Oncogene, 18, 2718–2727.

  • Llanos S, Clark PA, Rowe J and Peters G . (2001). Nat. Cell Biol., 3, 445–452.

  • Rizos H, Darmanian AP, Mann GJ and Kefford RF . (2000). Oncogene, 19, 2978–2985.

  • Rossi F, Labourier E, Forné T, Divita G, Derancourt J, Riou JF, Antoine E, Cathala G, Brunel C and Tazi J . (1996). Nature, 381, 80–82.

  • Serrano M, Hannon GJ and Beach D . (1993). Nature, 366, 704–707.

  • Sherr CJ . (1998). Genes Dev., 12, 2984–2991.

  • Sherr CJ . (2001). Nat. Rev. Mol. Cell. Biol., 10, 731–737 (review).

  • Vaughn JL, Goodwin RH, Tompkins GJ and McCawley P . (1977). In Vitro, 13, 213–217.

  • Weber JD, Taylor LJ, Roussel MF, Sher CJ and Bar-Sagi D . (1999). Nat. Cell Biol., 1, 20–26.

  • Weber JD, Jeffers JR, Tehg JE, Randle DH, Lozano G, Roussel MF, Scherr CJ and Zambetti GP . (2000). Genes Dev., 14, 2358–2365.

  • Wei W, Hemmer RM and Sedivy JM . (2001). Mol. Cell Biol., 21, 6748–6757.

  • Zhang Y and Xiong Y . (1999). Mol. Cell., 3, 579–591.

  • Zhang Y, Xiong Y . (2001). Cell Growth Differ., 12, 175–186.

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Acknowledgements

This work was supported by a Grant (ARC 5915) from the Association pour la Recherche centre le Cancer (ARC) Villejuif, France. We are grateful to Dr Gazzeri for providing us with GST constructions. We also acknowledge the help of Dr A Cantereau for confocal microscopy studies.

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Authors and Affiliations

  1. Institut de Biologie Moléculaire et d'Ingénierie Génétique (IBMIG), 40 Avenue du recteur Pineau, 86022 Poitiers, France

    Ayrault Olivier, Karayan Lucie, Larsen Christian-Jacques & Séité Paule

  2. UFR de Pharmacie, 51, rue Cognacq-Jay, Reims, 51096, France

    Riou Jean-François

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  1. Ayrault Olivier
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  2. Karayan Lucie
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Correspondence to Séité Paule.

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Olivier, A., Lucie, K., Jean-François, R. et al. Delineation of the domains required for physical and functional interaction of p14ARF with human topoisomerase I. Oncogene 22, 1945–1954 (2003). https://doi.org/10.1038/sj.onc.1206214

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