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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3-4
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pubmed:dateCreated |
2001-11-23
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pubmed:abstractText |
Individually over-expressed chaperones can interfere with cytotoxicity and aggregation of polyglutamine proteins in disease models. As chaperones cooperate, the analysis of suppression or reversal of polyglutamine pathology may require ways to up-regulate multiple chaperone coding genes. This condition might be achieved by exogenous expression of de-repressed forms of heat shock transcription factor 1 (HSF1), which mediates induction of several genes coding cytosolic and nuclear chaperones. Here we present the rationale behind this possible approach and the caveats, and employ a non-neuronal cell system to test whether Ataxin-1 aggregation can be modulated by de-repressed HSF1 mutants through augmented expression of chaperone coding genes. In our experiments, HSF1 mutants have induced heat shock protein 70 and Human DnaJ (HDJ)-1 to intermediate levels. Cells expressing such mutants also showed partial reduction of Ataxin-1 [31Q] aggregation. A consolidated positive outcome of these tests in cellular models would encourage experiments in transgenic mice and prospects for pharmacological modulation of HSF1 activity or delivery.
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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/Cytotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP40 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ataxin-1,
http://linkedlifedata.com/resource/pubmed/chemical/heat shock transcription factor,
http://linkedlifedata.com/resource/pubmed/chemical/polyglutamine
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pubmed:status |
MEDLINE
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pubmed:issn |
0361-9230
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
353-62
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11719272-Animals,
pubmed-meshheading:11719272-Cytotoxins,
pubmed-meshheading:11719272-DNA-Binding Proteins,
pubmed-meshheading:11719272-Fibroblasts,
pubmed-meshheading:11719272-Gene Deletion,
pubmed-meshheading:11719272-Gene Expression Regulation,
pubmed-meshheading:11719272-HSP40 Heat-Shock Proteins,
pubmed-meshheading:11719272-HSP70 Heat-Shock Proteins,
pubmed-meshheading:11719272-HeLa Cells,
pubmed-meshheading:11719272-Heat-Shock Proteins,
pubmed-meshheading:11719272-Humans,
pubmed-meshheading:11719272-Mice,
pubmed-meshheading:11719272-Molecular Chaperones,
pubmed-meshheading:11719272-Mutagenesis,
pubmed-meshheading:11719272-Nerve Tissue Proteins,
pubmed-meshheading:11719272-Nuclear Proteins,
pubmed-meshheading:11719272-Peptides,
pubmed-meshheading:11719272-Transcription Factors,
pubmed-meshheading:11719272-Transcriptional Activation,
pubmed-meshheading:11719272-Trinucleotide Repeats
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pubmed:articleTitle |
Analysis of heat shock transcription factor for suppression of polyglutamine toxicity.
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pubmed:affiliation |
Dibit, San Raffaele Scientific Institute, Milano, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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