Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis
2007 (English)In: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 14, no 3, 411-421 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2007. Vol. 14, no 3, 411-421 p.
p53, hypoxia, apoptosis, microarray analysis, p53 target genes
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:kth:diva-6653DOI: 10.1038/sj.cdd.4402022ISI: 000244275400004ScopusID: 2-s2.0-33847077136OAI: oai:DiVA.org:kth-6653DiVA: diva2:11423
QC 201009072006-12-152006-12-152014-11-17Bibliographically approved