title: Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization.
abstract: Sequence-specific DNA binding is a major activity of the tumor suppressor p53 and a prerequisite for the transactivating potential of the protein. p53 interaction with target DNA is tightly regulated by various mechanisms, including binding of different components of the transcription machinery, post-translational modifications, and interactions with other factors that modulate p53 transactivation in a cell context- and promoter-specific manner. The bi-functional redox factor 1 (Ref-1/APE1) has been identified as one of the factors, which can stimulate p53 DNA binding by redox-dependent as well as redox-independent mechanisms. Whereas stimulation of p53 DNA binding by the redox activities of Ref-1 is understood quite well, little is known about mechanisms that underlie the redox-independent effects of Ref-1. We report in this study a previously unknown activity of Ref-1 as a factor promoting tetramerization of p53. We demonstrate that Ref-1 promotes association of dimers into tetramers, and de-stacking of higher oligomeric forms into the tetrameric form in vitro, thereby enhancing p53 binding to target DNA.
authors.affiliation: Heinrich-Pette-Institute for Experimental Virology and Immunology at the University of Hamburg, Martinistr. 52, D-20251 Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hanson
authors.forename: Ella
authors.initials: E
authors.lastname: Kim
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Deppert
mesh_terms: D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D019281:Dimerization; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase