rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5773
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pubmed:dateCreated |
2006-4-28
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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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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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...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:AntonssonBrunoB,
pubmed-author:BassikMichael CMC,
pubmed-author:BernasconiPaulaP,
pubmed-author:BrandtGabriel SGS,
pubmed-author:FisherJillJ,
pubmed-author:GlimcherLaurie HLH,
pubmed-author:HetzClaudioC,
pubmed-author:IwakoshiNeal NNN,
pubmed-author:KorsmeyerStanley JSJ,
pubmed-author:LeeAnn-HweeAH,
pubmed-author:SchinzelAnnaA
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
312
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
572-6
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pubmed:dateRevised |
2009-11-19
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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
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pubmed:year |
2006
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pubmed:articleTitle |
Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha.
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pubmed:affiliation |
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA. chetz@hsph.harvard.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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