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

被引:103
作者
Martoriati, A
Doumont, G
Alcalay, M
Bellefroid, E
Pelicci, PG
Marine, JC
机构
[1] Flanders Interuniv Inst Biotechnol VIB, Lab Mol Canc Biol, B-9052 Ghent, Belgium
[2] Free Univ Brussels, ULB, IBMM, Unit Mol Embryol, Gosselies, Belgium
[3] European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy
[4] FIRC, Inst Mol Oncol, I-20139 Milan, Italy
关键词
apoptosis; dapk1; p53; Mdm4;
D O I
10.1038/sj.onc.1208256
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 p19(ARF)/p53-dependent apoptotic checkpoint, our results suggest that Dapk1 participates in a new positive feedback loop controlling p53 activation and apoptosis.
引用
收藏
页码:1461 / 1466
页数:6
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