Regulation of the specific dna binding activity of xenopus laevis p53: evidence for conserved regulation through the carboxy-terminus of the protein

ABSTRACT Recombinant human p53 isolated either from _E. COLI_ or from insect cells is poorly active for binding to DNA but it can be dramatically stimulated by phosphorylation, antibody

binding to the carboxy-terminal negative regulatory domain, short peptides derived from this negative regulatory domain or short single strands of DNA. We report here that _XENOPUS_ p53 has

a very similar behavior. Using a new set of monoclonal antibodies directed either to the amino- or the carboxy-terminus of _XENOPUS_ p53, we demonstrate that the frog protein can be

activated by specific carboxy-terminus monoclonal antibodies in order to bind to human p53 DNA response element. In addition, we report that such activation of both humans and frogs protein

can also be achieved by small peptides derived from the carboxy-terminus of both p53. Although, the sequence of this region is not conserved in the various p53 species, the presence of

conserved basic residues indicates that such activation is charge-dependent. This is confirmed by the finding that small poly-lysine peptides can activate both human and _XENOPUS_ p53. _IN

VIVO_ expression of _XENOPUS_ p53 indicates that this protein is able to transactivate a wide variety of human p53 response elements as long as the experiments are performed at 32°C since

activity at 37°C, a temperature well above the natural temperature of _XENOPUS_, is lost. Finally, we demonstrate that human mdm2 is able to down regulate the transcriptional activity of

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June 2022 AUTHOR INFORMATION Author notes * Anne-Claire Hardy Bessard Present address: Unité d'Oncologie Médicale, Hopital Saint Louis, avenue C. Vellefaux, Paris, 75010, France * Edith

Garay Present address: Centro de Neurobiologia, Apartado Postal 1–1141, 76001, Queretaro, Qro., C.P., Mexique * Yann Legros Present address: Pharmacia Biotech Parc Technologique, rue René

Razel, Saclay, Orsay Cedex, 91898, France * Thierry Soussi Present address: UMR 218 du CNRS, Institut Curie, Pavillon Trouillet Rossignol, 26 rue d'Ulm, Paris, cedex 05 75231, France

AUTHORS AND AFFILIATIONS * U301 INSERM, Institut de Génétique Moléculaire 27, rue J Dodu, Paris, 75010 Anne-Claire Hardy Bessard, Edith Garay, Virginie Lacronique, Yann Legros, Christel

Demarquay, Armelle Houque & Thierry Soussi * CNRS UMR 9921 UFR Pharmacie 15 Av Flahault, Montpellier, Cedex 01 34060, France Jean Michel Portefaix & Claude Granier Authors *

Anne-Claire Hardy Bessard View author publications You can also search for this author inPubMed Google Scholar * Edith Garay View author publications You can also search for this author

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AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bessard, AC., Garay, E., Lacronique, V. _et al._ Regulation of the specific DNA binding activity of _XENOPUS

LAEVIS_ p53: evidence for conserved regulation through the carboxy-terminus of the protein. _Oncogene_ 16, 883–890 (1998). https://doi.org/10.1038/sj.onc.1201598 Download citation *

Received: 06 August 1997 * Revised: 26 September 1997 * Accepted: 26 September 1997 * Published: 03 March 1998 * Issue Date: 19 February 1998 * DOI: https://doi.org/10.1038/sj.onc.1201598

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clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * p53 * xenopus * manoclonal antibodies * transactivation