TY - JOUR
T1 - dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53
AU - Martoriati, Alain
AU - Doumont, Gilles
AU - Alcalay, Myriam
AU - Bellefroid, Eric
AU - Pelicci, Pier Giuseppe
AU - Marine, Jean Christophe
PY - 2005/2/17
Y1 - 2005/2/17
N2 - 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.
AB - 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.
KW - Apoptosis
KW - dapk1
KW - Mdm4
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=14844337826&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14844337826&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208256
DO - 10.1038/sj.onc.1208256
M3 - Article
C2 - 15608685
AN - SCOPUS:14844337826
VL - 24
SP - 1461
EP - 1466
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 8
ER -