DSpace Repository

Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis

Show simple item record

dc.contributor.author Sadashivam, Subhashini
dc.contributor.author Gupta, Sanjeev
dc.contributor.author Radha, Vegesna
dc.contributor.author Batta, Kiran
dc.contributor.author Kundu, Tapas K
dc.contributor.author Swarup, Ghanshyam
dc.date.accessioned 2012-02-14T11:12:43Z
dc.date.available 2012-02-14T11:12:43Z
dc.date.issued 2005-01-20
dc.identifier 09509232 en_US
dc.identifier.citation Oncogene 24(4), 627-636 (2005) en_US
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/412
dc.description Restricted Access en_US
dc.description.abstract The tumor suppressor protein p53 regulates transcription of many genes that mediate cell cycle arrest, apoptosis, DNA repair and other cellular responses. Here we show that Ipaf, a human CED-4 homologue and an activator of caspase-1, is induced by p53. Overexpression of p53 by transfection in U2OS and A549 cells increased Ipaf mRNA levels. Treatment of p53-positive cell lines U2OS and MCF-7 with the DNA damaging drug, doxorubicin, which increases p53 protein level, induced expression of Ipaf mRNA but similar treatment of MCF-7-mp53 (a clone of MCF-7 cells expressing mutant p53) and p53-negative K562 cells showed much less induction of Ipaf gene expression. Expression analysis for Ipaf mRNA in doxorubicin-treated human tumor cell lines suggests that p53-dependent as well as p53-independent mechanisms are involved in the regulation of Ipaf gene expression in a cell-type-specific manner. The Ipaf promoter was activated by normal p53 but not by His273 mutant of p53. A functional p53-binding site was identified in the Ipaf promoter. A dominant-negative mutant of Ipaf inhibited p53-induced and doxorubicin-induced apoptosis by about 50%. Ipaf-directed small hairpin RNA downregulated p53-induced Ipaf gene expression and also reduced p53-induced apoptosis. Doxorubicin-induced apoptosis was also inhibited by Ipaf-directed small hairpin RNA. Our results show that p53 can directly induce Ipaf gene transcription, which contributes to p53-dependent apoptosis in at least some human cells. en_US
dc.description.uri http://dx.doi.org/10.1038/sj.onc.1208201 en_US
dc.language.iso en en_US
dc.publisher Nature Publishing Group en_US
dc.rights © 2005 Nature Publishing Group en_US
dc.subject p53 en_US
dc.subject ipaf en_US
dc.subject caspase-1 en_US
dc.subject apoptosis en_US
dc.subject transcriptional activation en_US
dc.subject gene expression en_US
dc.title Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis en_US
dc.type Article en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account