Linked Life Data

18005063

Source:http://linkedlifedata.com/resource/pubmed/id/18005063

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-11-21
pubmed:abstractText
Several causal missense mutations in protein kinase C gamma (gamma PKC) gene have been found in spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that mutant gamma PKC found in SCA14 is susceptible to two types of aggregation, cytoplasmic dot-like and perinuclear massive aggregation, and causes cell death in Chinese hamster ovary cells. Long-term time-lapse imaging revealed that firstly accumulated dot-like aggregation of mutant gamma PKC-green fluorescent protein (GFP) gradually formed perinuclear massive aggregations, followed by cell death. However, it remains unclear how aggregate formation of mutant gamma PKC causes cell death. In the present study, we examined whether these mutant aggregations affect the ubiquitin-proteasome system (UPS) and endoplasmic reticular (ER) stress. Two mutant gamma PKC-GFPs (S119P and G128D) were strongly ubiquitinated, and dot-like aggregations of these mutants were ubiquitin-positive and colocalized with proteasome 20S. Furthermore, proteasome activity in cells with aggregates, especially massive ones, was significantly decreased. Aggregate formation of mutant gamma PKC-GFP induced phosphorylation of PERK (PKR-like ER kinase) and nuclear expression of CHOP (C/EBP homologous protein), hallmarks of ER stress and subsequently activated caspase-3. These results indicate that aggregate formation of mutant gamma PKC found in SCA14 impairs UPS and induces ER stress, leading to apoptotic cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3126-40
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18005063-Animals, pubmed-meshheading:18005063-Aspartic Acid, pubmed-meshheading:18005063-CHO Cells, pubmed-meshheading:18005063-Caspases, pubmed-meshheading:18005063-Cell Death, pubmed-meshheading:18005063-Cricetinae, pubmed-meshheading:18005063-Cricetulus, pubmed-meshheading:18005063-Endoplasmic Reticulum, pubmed-meshheading:18005063-Glycine, pubmed-meshheading:18005063-Green Fluorescent Proteins, pubmed-meshheading:18005063-Humans, pubmed-meshheading:18005063-Immunoprecipitation, pubmed-meshheading:18005063-Mutation, pubmed-meshheading:18005063-Proline, pubmed-meshheading:18005063-Proteasome Endopeptidase Complex, pubmed-meshheading:18005063-Protein Kinase C, pubmed-meshheading:18005063-Protein Processing, Post-Translational, pubmed-meshheading:18005063-Serine, pubmed-meshheading:18005063-Stress, Physiological, pubmed-meshheading:18005063-Time Factors, pubmed-meshheading:18005063-Transfection, pubmed-meshheading:18005063-Ubiquitin
pubmed:year
2007
pubmed:articleTitle
Aggregate formation of mutant protein kinase C gamma found in spinocerebellar ataxia type 14 impairs ubiquitin-proteasome system and induces endoplasmic reticulum stress.
pubmed:affiliation
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't