Linked Life Data

15750336

Source:http://linkedlifedata.com/resource/pubmed/id/15750336

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-3-7
pubmed:abstractText
Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder caused by expansion of the polyglutamine tract in the SCA1 gene product, ataxin-1. Using d2EGFP, a short-lived enhanced green fluorescent protein, we investigated whether polyglutamine-expanded ataxin-1 affects the function of the proteasome, a cellular multicatalytic protease that degrades most misfolded proteins and regulatory proteins. In Western blot analysis and immunofluorescence experiments, d2EGFP was less degraded in HEK 293T cells transfected with ataxin-1(82Q) than in cells transfected with lacZ or empty vector controls. To test whether the stability of the d2EGFP protein was due to aggregation of ataxin-1, we constructed a plasmid carrying ataxin-1-Delta114, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of ataxin-1-Delta114 aggregates and the amount of d2EGFP were drastically reduced in cells containing ataxin-1-Delta114. Furthermore, d2EGFP localization experiments showed that polyglutamine-expanded ataxin-1 inhibited the general function of the proteasome activity. Taken together, these results demonstrate that polyglutamine-expanded ataxin-1 decreases the activity of the proteasome, implying that a disturbance in the ubiquitin-proteasome pathway is directly involved in the development of spinocerebellar ataxia type1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1016-8478
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product.
pubmed:affiliation
Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't