Linked Life Data

12584735

Source:http://linkedlifedata.com/resource/pubmed/id/12584735

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-2-13
pubmed:abstractText
Caspases exist as zymogens, and are activated by various extracellular stimuli, leading to apoptosis. One such stimulus is Fas/CD95, a member of the tumor necrosis factor receptor family, providing one means of cytotoxic T lymphocyte (CTL)-mediated cell lysis. Clinical evidence has shown that administration of cytokine leads to regression in selected patients with renal cell carcinomas (RCCs). Interferon-gamma (IFN-gamma) indicates its contribution to anti-tumor activity of immune cells. IFN-gamma elicits its effect through the transcription factor signal transducer and activator of transcription-1 (STAT-1), and through interferon regulatory factor-1 (IRF-1), one of the target genes of STAT-1. Our previous study demonstrated an increase in the susceptibility of ACHN cells, established from RCC, to Fas-mediated apoptosis by IFN-gamma, and the inhibition of this effect by the caspase-3 and -7 inhibitor, DEVD-CHO. We demonstrated the following phenomena in IFN-gamma-treated ACHN cells: 1) enhanced transcription of caspase-1, 3 and 7 mRNAs without any change in cleavage of their substrates; 2) increased cleavage DEVD (specific for caspase-3 and 7), but not YVAD (for caspase-1) or DMQD (for caspase-3), after anti-Fas/CD95 MAb treatment; 3) activation of the STAT-1 and IRF-1 pathway; and 4) partial abrogation of the IFN-gamma-induced increase in Fas-mediated apoptosis by antisense IRF-1 oligodeoxynucleotide. These results suggest that IRF-1 plays a pivotal role in the IFN-gamma-mediated-enhancement of Fas/CD95-mediated apoptosis, through regulation of DEVD-CHO-sensitive caspases, most likely caspase-7.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95, http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CASP7 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 7, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, 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/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
400-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Role of IRF-1 and caspase-7 in IFN-gamma enhancement of Fas-mediated apoptosis in ACHN renal cell carcinoma cells.
pubmed:affiliation
Division of Molecular Oncology, Department of Signal Transduction Research, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. ytomita@med.niigata-u.ac.jp
pubmed:publicationType
Journal Article