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

Alain Martoriati, Gilles Doumont, Myriam Alcalay, Eric Bellefroid, Pier Giuseppe Pelicci, Jean Christophe Marine

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1461-1466
Number of pages6
JournalOncogene
Volume24
Issue number8
DOIs
Publication statusPublished - Feb 17 2005

Keywords

  • Apoptosis
  • dapk1
  • Mdm4
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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