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 |