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  • Original Paper
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Human ARF protein interacts with Topoisomerase I and stimulates its activity

Abstract

The ARF gene (p19ARF in mouse and p14ARF in man) has become a central actor of the cell cycle regulation process as it participates to the ARF-MDM2-p53 pathway and the Rb-E2F-1 pathway. By use of immunoprecipitation and Western blotting (IP/WB), we now show that ARF physically associates with Topoisomerase I (Topo I). ARF-Topo I immune complexes were detected in SF9 insect cells infected with recombinant baculoviruses encoding the two genes as well as in 293 cells that express endogeneously these proteins. Preparations of a GST–ARF recombinant protein stimulated the DNA relaxation activity of Topo I but, in contrast, had no effect on the decatenation activity of Topo II. The Topo I stimulation was also detected in cell extracts of SF9 cells expressing both proteins. A confocal microscopy study indicated that part of ARF and Topo I colocalized in the granular component structure of the nucleolus. As a whole, our data indicate that Topo I is a new partner of ARF and suggest that ARF is involved in cell reactions that require Topo I.

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Acknowledgements

This work was supported by grants from the Association pour la Recherche contre le Cancer (ARC, contrat 5524), and from the Ligue Nationale contre le Cancer (Comités de la Vienne et de la Charente Maritime). L Karayan held a postdoctoral fellowship from la Ligue nationale contre le Cancer.

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Karayan, L., Riou, JF., Séité, P. et al. Human ARF protein interacts with Topoisomerase I and stimulates its activity. Oncogene 20, 836–848 (2001). https://doi.org/10.1038/sj.onc.1204170

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