Source:http://linkedlifedata.com/resource/pubmed/id/19640899
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-9-29
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| pubmed:abstractText |
Expression and activity of the germinal center kinase [corrected] SLK are increased during kidney development and recovery from renal ischemia-reperfusion injury. SLK promotes apoptosis, in part, via pathway(s) involving apoptosis signal-regulating kinase-1 and p38 mitogen-activated protein kinase. This study addresses the role of p53 as a potential effector of SLK. p53 transactivation was measured after transient transfection of a luciferase reporter plasmid that contains a p53 cis-acting enhancer element. Overexpression of SLK in COS-1 cells and cotransfection of SLK and p53-wild type (wt) cDNAs in glomerular epithelial cells (GECs) stimulated p53 transactivational activity, as measured by a p53 response element-driven luciferase reporter. In GECs, chemical anoxia followed by glucose reexposure (in vitro ischemia-reperfusion) increased p53 reporter activity, and this increase was amplified by overexpression of SLK. Expression of SLK induced p53 phosphorylation on serine (S)-33 and S315. In GECs, cotransfection of SLK with p53-wt, p53-S33A, p53-S315A, or p53-S33A+S315A mutants showed that only the double mutation abolished the SLK-induced increase in p53 reporter activity. SLK-induced stimulation of p53 reporter activity was attenuated by inhibition of JNK. Overexpression of SLK amplified apoptosis induced by subjecting cells to in vitro ischemia-reperfusion injury, while ectopic expression of a dominant negative SLK mutant attenuated the ischemia-reperfusion-induced apoptosis. The p53 transactivation inhibitor pifithrin-alpha significantly attenuated the amount of apoptosis after ischemia-reperfusion and SLK overexpression. Thus SLK induces p53 phosphorylation and transactivation, which enhances apoptosis after in vitro ischemia-reperfusion injury.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/germinal center kinases,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1522-1466
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
297
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
F971-80
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| pubmed:dateRevised |
2011-4-28
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| pubmed:meshHeading |
pubmed-meshheading:19640899-Animals,
pubmed-meshheading:19640899-Anoxia,
pubmed-meshheading:19640899-Apoptosis,
pubmed-meshheading:19640899-COS Cells,
pubmed-meshheading:19640899-Cercopithecus aethiops,
pubmed-meshheading:19640899-Dogs,
pubmed-meshheading:19640899-Epithelial Cells,
pubmed-meshheading:19640899-Genes, Reporter,
pubmed-meshheading:19640899-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:19640899-Kidney,
pubmed-meshheading:19640899-MAP Kinase Signaling System,
pubmed-meshheading:19640899-Phosphorylation,
pubmed-meshheading:19640899-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19640899-Rats,
pubmed-meshheading:19640899-Reperfusion Injury,
pubmed-meshheading:19640899-Transcriptional Activation,
pubmed-meshheading:19640899-Tumor Suppressor Protein p53,
pubmed-meshheading:19640899-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2009
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| pubmed:articleTitle |
The Ste20-like kinase SLK promotes p53 transactivation and apoptosis.
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| pubmed:affiliation |
Div. of Nephrology, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, Quebec H3A1A1, Canada. andrey.cybulsky@mcgill.ca
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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