Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5773
pubmed:dateCreated
2006-4-28
pubmed:abstractText
Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response-termed the unfolded protein response (UPR)-mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme-1alpha (IRE1alpha). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1alpha signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1alpha that was essential for IRE1alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Bak1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Endoribonucleases, http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PERK kinase, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tunicamycin, http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer..., http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein, http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase, http://linkedlifedata.com/resource/pubmed/chemical/molecular chaperone GRP78, http://linkedlifedata.com/resource/pubmed/chemical/regulatory factor X transcription...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1095-9203
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
312
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
572-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16645094-Animals, pubmed-meshheading:16645094-Apoptosis, pubmed-meshheading:16645094-DNA-Binding Proteins, pubmed-meshheading:16645094-Endoplasmic Reticulum, pubmed-meshheading:16645094-Endoribonucleases, pubmed-meshheading:16645094-Gene Expression Regulation, pubmed-meshheading:16645094-Heat-Shock Proteins, pubmed-meshheading:16645094-Humans, pubmed-meshheading:16645094-Kidney, pubmed-meshheading:16645094-Liver, pubmed-meshheading:16645094-Mice, pubmed-meshheading:16645094-Mice, Knockout, pubmed-meshheading:16645094-Mitochondria, pubmed-meshheading:16645094-Molecular Chaperones, pubmed-meshheading:16645094-Nuclear Proteins, pubmed-meshheading:16645094-Phosphorylation, pubmed-meshheading:16645094-Protein Folding, pubmed-meshheading:16645094-Protein Structure, Tertiary, pubmed-meshheading:16645094-Protein-Serine-Threonine Kinases, pubmed-meshheading:16645094-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16645094-Recombinant Proteins, pubmed-meshheading:16645094-Signal Transduction, pubmed-meshheading:16645094-Transcription Factor CHOP, pubmed-meshheading:16645094-Transcription Factors, pubmed-meshheading:16645094-Tunicamycin, pubmed-meshheading:16645094-bcl-2 Homologous Antagonist-Killer Protein, pubmed-meshheading:16645094-bcl-2-Associated X Protein, pubmed-meshheading:16645094-eIF-2 Kinase
pubmed:year
2006
pubmed:articleTitle
Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha.
pubmed:affiliation
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA. chetz@hsph.harvard.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural