Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis

被引：0
作者：
T Liu
C Laurell
G Selivanova
J Lundeberg
P Nilsson
K G Wiman
机构：
[1] Cancer Center Karolinska (CCK),Department of Oncology–Pathology
[2] Karolinska Institute,Department of Gene Technology
[3] School of Biotechnology,undefined
[4] KTH – Royal Institute of Technology,undefined
[5] Microbiology and Tumor Biology Center (MTC),undefined
[6] Karolinska Institute,undefined
来源：
Cell Death & Differentiation | 2007年 / 14卷
关键词：
p53; hypoxia; apoptosis; microarray analysis; p53 target genes;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
p53 triggers apoptosis in response to cellular stress. We analyzed p53-dependent gene and protein expression in response to hypoxia using wild-type p53-carrying or p53 null HCT116 colon carcinoma cells. Hypoxia induced p53 protein levels and p53-dependent apoptosis in these cells. cDNA microarray analysis revealed that only a limited number of genes were regulated by p53 upon hypoxia. Most classical p53 target genes were not upregulated. However, we found that Fas/CD95 was significantly induced in response to hypoxia in a p53-dependent manner, along with several novel p53 target genes including ANXA1, DDIT3/GADD153 (CHOP), SEL1L and SMURF1. Disruption of Fas/CD95 signalling using anti-Fas-blocking antibody or a caspase 8 inhibitor abrogated p53-induced apoptosis in response to hypoxia. We conclude that hypoxia triggers a p53-dependent gene expression pattern distinct from that induced by other stress agents and that Fas/CD95 is a critical regulator of p53-dependent apoptosis upon hypoxia.
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页码：411 / 421
页数：10
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