Linked Life Data

18065495

Source:http://linkedlifedata.com/resource/pubmed/id/18065495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-3-3
pubmed:abstractText
Huntington's disease (HD) is caused by a polyglutamine (polyQ) expansion in the huntingtin (htt) protein. While aggregation is a pathological hallmark of HD and related polyQ expansion diseases, the role of aggregates has been disputed. Here we report that p21-activated kinase 1 (Pak1) binds to htt in vivo and in vitro. Pak1 colocalized with mutant htt (muhtt) aggregates in cell models and in human HD brains. Pak1 overexpression enhanced the aggregation of muhtt. Furthermore, we observed SDS-soluble wild-type htt (wthtt)-wthtt, wthtt-muhtt and muhtt-muhtt interactions, which were enhanced by the presence of Pak1. We show that Pak1 overexpression enhanced htt toxicity in cell models and neurons in parallel with its ability to promote aggregation, while Pak1 knockdown suppressed both aggregation and toxicity. Overexpression of either kinase-dead or wild-type Pak enhanced both aggregation and toxicity. Our data reveal a novel mechanism regulating muhtt oligomerization and toxicity and suggest that pathology may be at least partly dependent on soluble muhtt-muhtt interactions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
895-905
pubmed:dateRevised
2010-4-1
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity.
pubmed:affiliation
Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't