Linked Life Data

12163019

Source:http://linkedlifedata.com/resource/pubmed/id/12163019

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-8-6
pubmed:abstractText
FAD mutations in presenilin-1 (PS1) cause attenuation of the induction of the endoplasmic reticulum (ER)-resident chaperone GRP78/BiP under ER stress, due to disturbed function of IRE1, the sensor for accumulation of unfolded protein in the ER lumen. PERK, an ER-resident transmembrane protein kinase, is also a sensor for the unfolded protein response (UPR), causing phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) to inhibit translation initiation. Here, we report that the FAD mutant PS1 disturbs the UPR by attenuating both the activation of PERK and the phosphorylation of eIF2alpha. Consistent with the results of a disturbed UPR, inhibition of protein synthesis under ER stress was impaired in cells expressing PS1 mutants. These results suggest that mutant PS1 impedes general translational attenuation regulated by PERK and eIF2alpha, resulting in an increased load of newly synthesized proteins into the ER and subsequently increasing vulnerability to ER stress.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
FAD-linked presenilin-1 mutants impede translation regulation under ER stress.
pubmed:affiliation
Division of Psychiatry and Behavioral Proteomics, Department of Post-Genomics and Diseases, Course of Advanced Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Siuta, Osaka, Japan. kudo@psy.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't