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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
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pubmed:dateCreated |
1997-7-16
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pubmed:abstractText |
Interferon (IFN)-gamma increases the sensitivity of tumor cell lines, many of which are p53 mutants, to tumor necrosis factor-alpha-mediated and anti-Fas antibody-mediated cell death. To better understand the mechanism of IFN-gamma action in modulating the cell death response independently of p53 function, we analyzed the death of the human colon adenocarcinoma cell line, HT-29, following treatment with IFN-gamma and various cytotoxic agents. Here we show that IFN-gamma modulates cell death by sensitizing the cells to killing by numerous pro-apoptotic stimuli but not pro-necrotic stimuli. Furthermore, we show that select genes from several important apoptosis-related gene families are induced by IFN-gamma, including the apoptosis-signaling receptors CD95 (Fas/APO-1) and TNFR 1 and interleukin-1beta-converting enzyme (Ice) family members Ice, CPP32 (Yama, apopain), ICErel-II (TX, Ich-2), Mch-3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH, FLICE). Of the bcl-2 family members, IFN-gamma directly induced bak but notably not bax, which is activated by p53. The IFN-responsive transcriptional activator interferon regulatory factor-1 was also strongly induced and translocated into the nucleus following IFN-gamma treatment. We propose that IFN-gamma modulates a p53-independent apoptotic pathway by both directly and indirectly inducing select apoptosis-related genes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16351-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9195941-Apoptosis,
pubmed-meshheading:9195941-Cycloheximide,
pubmed-meshheading:9195941-DNA-Binding Proteins,
pubmed-meshheading:9195941-Gene Expression Regulation,
pubmed-meshheading:9195941-HT29 Cells,
pubmed-meshheading:9195941-Humans,
pubmed-meshheading:9195941-Interferon Regulatory Factor-1,
pubmed-meshheading:9195941-Interferon-gamma,
pubmed-meshheading:9195941-Phosphoproteins,
pubmed-meshheading:9195941-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:9195941-RNA, Messenger,
pubmed-meshheading:9195941-Tumor Suppressor Protein p53
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pubmed:year |
1997
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pubmed:articleTitle |
Interferon-gamma modulates a p53-independent apoptotic pathway and apoptosis-related gene expression.
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pubmed:affiliation |
LXR Biotechnology Inc., Richmond, California 94804, USA.
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pubmed:publicationType |
Journal Article
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