Human ARF protein interacts with topoisomerase I and stimulates its activity

Oncogene. 2001 Feb 15;20(7):836-48. doi: 10.1038/sj.onc.1204170.


The ARF gene (p19(ARF) in mouse and p14(ARF) 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 endogenously 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Cell Compartmentation
  • Cell Nucleolus / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / metabolism*
  • DNA Topoisomerases, Type II / metabolism
  • Enzyme Activation
  • Humans
  • Nucleic Acid Conformation
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Spodoptera / cytology
  • Tumor Suppressor Protein p14ARF


  • Cyclin-Dependent Kinase Inhibitor p16
  • Proteins
  • Recombinant Proteins
  • Tumor Suppressor Protein p14ARF
  • DNA Topoisomerases, Type I
  • DNA Topoisomerases, Type II