The antitumor agent doxorubicin binds to Fanconi anemia group F protein

Bioorg Med Chem. 2012 Nov 1;20(21):6248-55. doi: 10.1016/j.bmc.2012.09.015. Epub 2012 Sep 16.

Abstract

Doxorubicin, a commonly used cancer chemotherapy agent, elicits several potent biological effects, including synergistic-antitumor activity in combination with cisplatin. However, the mechanism of this synergism remains obscure. Here, we employed an improved T7 phage display screening method to identify Fanconi anemia group F protein (FANCF) as a doxorubicin-binding protein. The FANCF-doxorubicin interaction was confirmed by pull-down assay and SPR analysis. FANCF is a component of the Fanconi anemia complex, which monoubiquitinates D2 protein of Fanconi anemia group as a cellular response against DNA cross-linkers such as cisplatin. We observed that the monoubiquitination was inhibited by doxorubicin treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Binding Sites / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Fanconi Anemia Complementation Group D2 Protein / antagonists & inhibitors
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Fanconi Anemia Complementation Group F Protein / antagonists & inhibitors*
  • Fanconi Anemia Complementation Group F Protein / chemistry
  • HEK293 Cells
  • Humans
  • Kinetics
  • Molecular Structure
  • Peptide Library
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship
  • Surface Plasmon Resonance

Substances

  • Antineoplastic Agents
  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group F Protein
  • Peptide Library
  • Recombinant Proteins
  • Doxorubicin