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Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization

Oncogene volume 24, pages 1641–1647 (2005)Cite this article

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.

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Acknowledgements

We thank Ms Martina-Hintz-Malchow for careful preparation of the manuscript. This study was supported by Grant 10-1417-De4 from the Deutsche Krebshilfe and Grant I-478-44.13/1996 from the German–Israeli Foundation (GIF). The Heinrich-Pette-Institut is supported by the Freie und Hausestadt Hamburg and the Bundesministerium fur Gesundheit.

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Author notes

  1. Sven Hanson

    Present address: Department of Craniofacial Development, King's College, Guy's Campus, Tower Floor 27, London, SE1 9RT, UK

  2. Ella Kim

    Present address: Neuro-Oncology Group, Department of Neurosurgery, University of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, D-23538, Luebeck, Germany

Authors and Affiliations

  1. Heinrich-Pette-Institute for Experimental Virology and Immunology at the University of Hamburg, Martinistr. 52, D-20251, Hamburg, Germany

    Sven Hanson, Ella Kim & Wolfgang Deppert

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  1. Sven Hanson
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Correspondence to Wolfgang Deppert.

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Hanson, S., Kim, E. & Deppert, W. Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization. Oncogene 24, 1641–1647 (2005). https://doi.org/10.1038/sj.onc.1208351

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