Linked Life Data

11278723

Source:http://linkedlifedata.com/resource/pubmed/id/11278723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2001-4-24
pubmed:abstractText
When accumulation of a malfolded protein in the endoplastic reticulum (ER) is induced by various adverse conditions, such as hypoxia, glucose starvation, and perturbation of calcium homeostasis, cells respond to the stress by increasing transcription of genes encoding ER molecular chaperones, a process known as unfolded protein response. The signaling is initiated by IRE1s, ER stress sensors. Alternatively, excessive stress to the ER results in apoptosis. Caspase-12 is known to be essential for this ER stress-induced apoptosis. In this study, we analyzed the detailed regulatory mechanisms of IRE1s during ER stress. We identified c-Jun N-terminal inhibitory kinase (JIK) as a binding partner of IRE1alpha, and JIK was seen to modulate IRE1alpha-TRAF2 (tumor necrosis factor receptor-associated factor 2) complex formation and the resultant alteration to c-Jun N-terminal kinase signaling from IRE1s in response to ER stress. We also demonstrated that TRAF2 interacts with procaspase-12 and promotes the clustering of procaspase-12 and its activation by cleavage in response to ER stress. These results indicate that TRAF2 plays crucial roles not only in the signaling of the c-Jun N-terminal kinase pathway but also in activation of caspase-12 to transduce signals from IRE1s. Thus, we provide a missing link in the ER stress-induced apoptosis-signaling pathway, one which connects the stress sensor molecule IRE1 and the activation of caspase-12.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13935-40
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11278723-Apoptosis, pubmed-meshheading:11278723-Caspase 12, pubmed-meshheading:11278723-Caspases, pubmed-meshheading:11278723-Cell Line, pubmed-meshheading:11278723-Dimerization, pubmed-meshheading:11278723-Dose-Response Relationship, Drug, pubmed-meshheading:11278723-Endoplasmic Reticulum, pubmed-meshheading:11278723-Enzyme Activation, pubmed-meshheading:11278723-Humans, pubmed-meshheading:11278723-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:11278723-Mitogen-Activated Protein Kinase 8, pubmed-meshheading:11278723-Mitogen-Activated Protein Kinases, pubmed-meshheading:11278723-Mutation, pubmed-meshheading:11278723-Plasmids, pubmed-meshheading:11278723-Protein Binding, pubmed-meshheading:11278723-Protein Folding, pubmed-meshheading:11278723-Protein Precursors, pubmed-meshheading:11278723-Protein Structure, Tertiary, pubmed-meshheading:11278723-Proteins, pubmed-meshheading:11278723-Signal Transduction, pubmed-meshheading:11278723-Stress, Physiological, pubmed-meshheading:11278723-TNF Receptor-Associated Factor 2, pubmed-meshheading:11278723-Transfection, pubmed-meshheading:11278723-Tunicamycin, pubmed-meshheading:11278723-Two-Hybrid System Techniques
pubmed:year
2001
pubmed:articleTitle
Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress.
pubmed:affiliation
Department of Anatomy and Neuroscience, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. yoneda@anat2.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't