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dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53

Oncogene volume 24, pages 1461–1466 (2005)Cite this article

Abstract

The p53 tumour suppressor functions as a transcriptional activator, and several p53-inducible genes that play a critical proapoptotic role have been described. Moreover, p53 regulates the expression of various proteins participating in autoregulatory feedback loops, including proteins that negatively control p53 stability (Mdm2 and Pirh2) or modulate stress-induced phosphorylation of p53 on Ser-46 (p53DINP1 or Wip1), a key event for p53-induced apoptosis. Here, we describe a new systematic analysis of p53 targets using oligonucleotide chips, and report the identification of dapk1 as a novel p53 target. We demonstrate that dapk1 mRNA levels increase in a p53-dependent manner in various cellular settings. Both human and mouse dapk1 genomic loci contain DNA sequences that bind p53 in vitro and in vivo. Since dapk1 encodes a serine/threonine kinase previously shown to suppress oncogene-induced transformation by activating a p19ARF/p53-dependent apoptotic checkpoint, our results suggest that Dapk1 participates in a new positive feedback loop controlling p53 activation and apoptosis.

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Acknowledgements

We thank Alberto Gobbi and Manuella Capillo for help with mice, Simone Minardi, Loris Bernard and Laura Tizzoni for technical help with the Affymetrix and Q-PCR technologies. We also thank M Rouselle and C Sherr (St Jude Children's Research Hospital, Memphis, TN, USA) for the pMTArf cell line, R Jaenisch (Whitehead Institute for Biomedical Research, Cambridge, USA) for the p53-deficient ES cells and K Vousden for the SAOS-2-p53 cell line. A Martoriati and G Doumont were supported by grants from the FNRS, FRIA and Télévie, respectively. This work was supported in part by grants from FB Insurance, AICR and ‘Fédération Belge contre le Cancer’.

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Author notes

  1. Alain Martoriati and Gilles Doumont: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory For Molecular Cancer Biology, Flanders Interuniversity Institute for Biotechnology (VIB), Technologiepark, 927, Ghent, B-9052, Belgium

    Alain Martoriati, Gilles Doumont & Jean-Christophe Marine

  2. Unit of Molecular Embryology, Free University of Brussels (ULB-IBMM), Gosselies, Belgium

    Alain Martoriati & Eric Bellefroid

  3. Department of Experimental Oncology, European Institute of Oncology, 435 Via Ripamonti, Milan, 20141, Italy

    Myriam Alcalay & Pier Giuseppe Pelicci

  4. FIRC Institute of Molecular Oncology, Via Adamello, 16, Milan, 20139, Italy

    Gilles Doumont, Myriam Alcalay & Pier Giuseppe Pelicci

Authors
  1. Alain Martoriati
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  2. Gilles Doumont
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  3. Myriam Alcalay
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  4. Eric Bellefroid
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  5. Pier Giuseppe Pelicci
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  6. Jean-Christophe Marine
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Corresponding author

Correspondence to Jean-Christophe Marine.

Additional information

Supplementary information accompanies the paper on http://www.dmbr.ugent.be/lmcb/contents/p53targets/.

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Martoriati, A., Doumont, G., Alcalay, M. et al. dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53. Oncogene 24, 1461–1466 (2005). https://doi.org/10.1038/sj.onc.1208256

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