Linked Life Data

11550089

Source:http://linkedlifedata.com/resource/pubmed/id/11550089

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-9-10
pubmed:abstractText
A growing number of inherited neurodegenerative disorders, including Huntington's disease, have been shown to be caused by the expansion of CAG/polyglutamine repeats. The molecular mechanism underlying these disorders, however, has yet to be clarified. We and others previously demonstrated that caspase-8 was activated by proteolysis in association with the expression of extended polyglutamine. Here, we further analyzed the selectivity of caspases in the process mediated by extended polyglutamine. Among upstream caspases, caspase-10, a close homolog of caspase-8, was also proteolytically activated, but caspase-9 was not. Caspase-8 and -10 were recruited into nuclear aggregates of extended polyglutamine, where at least a fraction of these caspases was converted to the activated forms. Caspase-8 and -10 were co-immunoprecipitated with polyglutamine only when the polyglutamine was pathologically extended, whereas caspase-2, -3, -6, -7 and -9 were not co-immunoprecipitated with polyglutamine regardless of its size. A dominant-negative form of caspase-8 with a mutation at the catalytic cysteine residue inhibited polyglutamine-mediated nuclear apoptotic phenotype. These results suggest that caspase-8 and -10 are autoactivated as a result of close proximity of the proforms of these molecules that occurs due to aggregate formation, which reveals a novel toxic gain-of-function mechanism for the pathogenesis of CAG-repeat disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1350-9047
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
377-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Extended polyglutamine selectively interacts with caspase-8 and -10 in nuclear aggregates.
pubmed:affiliation
Department of Genetics, National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154-8509, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't