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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2003-5-12
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pubmed:abstractText |
Prior heat stress (HS) or the selective overexpression of hsp72 prevents apoptosis caused by exposure to metabolic inhibitors by protecting the mitochondrial membrane and partially reducing caspase-3 activation. Focal adhesion kinase (FAK), a tyrosine kinase, exhibits anti-apoptotic properties and is a potential target for degradation by caspase-3. This study tested the hypothesis that hsp72 interacts with FAK, preventing caspase-3-mediated degradation during ATP depletion. ATP depletion (5 mm NaCN and 5 mm 2-deoxy-d-glucose in the absence of medium glucose) caused FAK degradation within 15 min. FAK degradation was completely prevented by a caspase-3-specific inhibitor. HS induced the accumulation of hsp72, increased the interaction between hsp72 and FAK, and significantly inhibited FAK degradation during ATP depletion. Selective overexpression of wild-type hsp72 (but not hsp72DeltaEEVD) reproduced the protective effects of HS on FAK cleavage. Purified hsp72 prevented the degradation of FAK by caspase-3 in vitro in a dose-dependent manner without affecting caspase-3 activity. Interaction between hsp72 and FAK is critical because both exogenous ATP and deletion of the substrate-binding site decreased protection of FAK by hsp72. These data indicate that FAK is an early target of injury in cells exposed to metabolic inhibitors and demonstrate that hsp72 reduces caspase-3-mediated proteolysis of FAK, an anti-apoptotic protein.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyglucose,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/HSP72 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PXN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Paxillin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18214-20
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12611892-Adenosine Triphosphate,
pubmed-meshheading:12611892-Animals,
pubmed-meshheading:12611892-Apoptosis,
pubmed-meshheading:12611892-Binding Sites,
pubmed-meshheading:12611892-Caspase 3,
pubmed-meshheading:12611892-Caspases,
pubmed-meshheading:12611892-Cytoskeletal Proteins,
pubmed-meshheading:12611892-Deoxyglucose,
pubmed-meshheading:12611892-Dose-Response Relationship, Drug,
pubmed-meshheading:12611892-Enzyme Activation,
pubmed-meshheading:12611892-Epithelial Cells,
pubmed-meshheading:12611892-Focal Adhesion Kinase 1,
pubmed-meshheading:12611892-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:12611892-HSP72 Heat-Shock Proteins,
pubmed-meshheading:12611892-Heat-Shock Proteins,
pubmed-meshheading:12611892-Humans,
pubmed-meshheading:12611892-Immunoblotting,
pubmed-meshheading:12611892-Kidney,
pubmed-meshheading:12611892-Opossums,
pubmed-meshheading:12611892-Paxillin,
pubmed-meshheading:12611892-Phosphoproteins,
pubmed-meshheading:12611892-Precipitin Tests,
pubmed-meshheading:12611892-Protein-Tyrosine Kinases,
pubmed-meshheading:12611892-Time Factors
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pubmed:year |
2003
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pubmed:articleTitle |
hsp72 inhibits focal adhesion kinase degradation in ATP-depleted renal epithelial cells.
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pubmed:affiliation |
Renal Section, Department of Medicine, Boston Medical Center, Boston University, Boston, Massachusetts 02118-2518, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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