Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5852
pubmed:dateCreated
2007-11-9
pubmed:abstractText
Endoplasmic reticulum (ER) stress activates a set of signaling pathways, collectively termed the unfolded protein response (UPR). The three UPR branches (IRE1, PERK, and ATF6) promote cell survival by reducing misfolded protein levels. UPR signaling also promotes apoptotic cell death if ER stress is not alleviated. How the UPR integrates its cytoprotective and proapoptotic outputs to select between life or death cell fates is unknown. We found that IRE1 and ATF6 activities were attenuated by persistent ER stress in human cells. By contrast, PERK signaling, including translational inhibition and proapoptotic transcription regulator Chop induction, was maintained. When IRE1 activity was sustained artificially, cell survival was enhanced, suggesting a causal link between the duration of UPR branch signaling and life or death cell fate after ER stress. Key findings from our studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1095-9203
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
318
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
944-9
pubmed:dateRevised
2011-6-8
pubmed:meshHeading
pubmed-meshheading:17991856-Activating Transcription Factor 6, pubmed-meshheading:17991856-Animals, pubmed-meshheading:17991856-Animals, Genetically Modified, pubmed-meshheading:17991856-Apoptosis, pubmed-meshheading:17991856-Cell Line, pubmed-meshheading:17991856-Cell Survival, pubmed-meshheading:17991856-Disease Models, Animal, pubmed-meshheading:17991856-Endoplasmic Reticulum, pubmed-meshheading:17991856-Endoribonucleases, pubmed-meshheading:17991856-Humans, pubmed-meshheading:17991856-Kinetics, pubmed-meshheading:17991856-Membrane Proteins, pubmed-meshheading:17991856-Mice, pubmed-meshheading:17991856-Mutation, pubmed-meshheading:17991856-Protein Folding, pubmed-meshheading:17991856-Protein-Serine-Threonine Kinases, pubmed-meshheading:17991856-Proteins, pubmed-meshheading:17991856-Rats, pubmed-meshheading:17991856-Retina, pubmed-meshheading:17991856-Retinitis Pigmentosa, pubmed-meshheading:17991856-Rhodopsin, pubmed-meshheading:17991856-Signal Transduction, pubmed-meshheading:17991856-eIF-2 Kinase
pubmed:year
2007
pubmed:articleTitle
IRE1 signaling affects cell fate during the unfolded protein response.
pubmed:affiliation
Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94158, USA. Jonathan.Lin@ucsf.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural