Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-6-2
pubmed:abstractText
The accumulation of misfolded proteins stresses the endoplasmic reticulum (ER) and triggers cell death through activation of the multidomain proapoptotic BCL-2 proteins BAX and BAK at the outer mitochondrial membrane. The signaling events that connect ER stress with the mitochondrial apoptotic machinery remain unclear, despite evidence that deregulation of this pathway contributes to cell loss in many human degenerative diseases. In order to "trap" and identify the apoptotic signals upstream of mitochondrial permeabilization, we challenged Bax-/- Bak-/- mouse embryonic fibroblasts with pharmacological inducers of ER stress. We found that ER stress induces proteolytic activation of the BH3-only protein BID as a critical apoptotic switch. Moreover, we identified caspase-2 as the premitochondrial protease that cleaves BID in response to ER stress and showed that resistance to ER stress-induced apoptosis can be conferred by inhibiting caspase-2 activity. Our work defines a novel signaling pathway that couples the ER and mitochondria and establishes a principal apoptotic effector downstream of ER stress.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-10638761, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-10929711, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-10929712, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-10950869, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-11163212, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-11326099, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-11780124, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-12065594, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-12193789, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-12624178, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-15073321, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-15123740, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-15719025, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-15975932, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16365312, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16407291, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16446060, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16472117, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16495337, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16701639, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-16710362, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-17015486, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-17301078, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-17565364, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-17604722, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-17981125, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-18039139, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-18077368, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-8689682, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-8918887, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-9727491, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-9727492, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-9930704, http://linkedlifedata.com/resource/pubmed/commentcorrection/18426910-9989411
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3943-51
pubmed:dateRevised
2011-6-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress.
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