Source:http://linkedlifedata.com/resource/pubmed/id/17623484
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2007-7-30
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| pubmed:abstractText |
The 27 kDa heat shock protein 1 (HSP27) is a member of the ubiquitously expressed small heat shock protein family and has pleiotropic cytoprotective functions. Since HSP27 may act as a motor neuron survival factor, we analyzed the genetic contribution of the human HSPB1 gene (HSPB1) to the etiology of amyotrophic lateral sclerosis (ALS). In a cohort of sporadic ALS patients, we identified three rare genetic variations and one of which (c.-217T>C) targeted a conserved nucleotide of the Heat Shock Element (HSE) in the HSPB1 promoter. Since binding of Heat Shock Factor 1 (HSF1) to this HSE is essential for stress-induced transcription of HSPB1, we examined the effect of the c.-217C allele on transcriptional activity and HSF binding. The basal promoter activity of the HSPB1 c.-217C mutant allele decreased to 50% as compared to the wild-type promoter in neuronal and non-neuronal cells. Following heat shock, the HSE variant attenuated significantly the stress-related increase in transcription. Electrophoretic mobility shift assays demonstrated a dramatically reduced HSF-binding to the c.-217C mutant allele as compared to the c.-217T wild-type allele. In conclusion, our study underscores the importance of the c.-217T nucleotide for HSF binding and heat inducibility of HSPB1. Therefore, our study suggests that the functional HSPB1 variant may represent a genetic modifier in the pathogenesis of motor neuron disease; however, it is necessary to confirm this HSPB1 variant in additional ALS patients.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1098-1004
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| pubmed:author |
pubmed-author:CorsmitEllenE,
pubmed-author:De JonghePeterP,
pubmed-author:DierickInesI,
pubmed-author:HersmusNicoleN,
pubmed-author:IrobiJoyJ,
pubmed-author:JacobsAnA,
pubmed-author:JanssensSophieS,
pubmed-author:LemmensRobinR,
pubmed-author:RobberechtWimW,
pubmed-author:TheunsJessieJ,
pubmed-author:TimmermanVincentV,
pubmed-author:Van BroeckhovenChristineC,
pubmed-author:Van Den BoschLudoL
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| pubmed:issnType |
Electronic
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| pubmed:volume |
28
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
830
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:17623484-Animals,
pubmed-meshheading:17623484-Base Sequence,
pubmed-meshheading:17623484-COS Cells,
pubmed-meshheading:17623484-Cercopithecus aethiops,
pubmed-meshheading:17623484-Consensus Sequence,
pubmed-meshheading:17623484-DNA Mutational Analysis,
pubmed-meshheading:17623484-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:17623484-Female,
pubmed-meshheading:17623484-HSP27 Heat-Shock Proteins,
pubmed-meshheading:17623484-Heat-Shock Proteins,
pubmed-meshheading:17623484-Heat-Shock Response,
pubmed-meshheading:17623484-Humans,
pubmed-meshheading:17623484-Male,
pubmed-meshheading:17623484-Middle Aged,
pubmed-meshheading:17623484-Molecular Sequence Data,
pubmed-meshheading:17623484-Mutation,
pubmed-meshheading:17623484-Neoplasm Proteins,
pubmed-meshheading:17623484-Promoter Regions, Genetic,
pubmed-meshheading:17623484-Protein Binding,
pubmed-meshheading:17623484-Response Elements,
pubmed-meshheading:17623484-Transcription, Genetic
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| pubmed:year |
2007
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| pubmed:articleTitle |
Genetic variant in the HSPB1 promoter region impairs the HSP27 stress response.
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| pubmed:affiliation |
Peripheral Neuropathy Group, University of Antwerp, Universiteitsplein 1, Antwerpen, Belgium.
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| pubmed:publicationType |
Journal Article
|