Linked Life Data

19122239

Source:http://linkedlifedata.com/resource/pubmed/id/19122239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-3-2
pubmed:abstractText
Down-regulation of the unfolded protein response (UPR) can be therapeutically valuable in cancer treatment, and endoplasmic reticulum (ER)-resident chaperone proteins may thus be targets for developing novel chemotherapeutic strategies. ERdj5 is a novel ER chaperone that regulates the ER-associated degradation of misfolded proteins through its associations with EDEM and the ER stress sensor BiP. To investigate whether ERdj5 can regulate ER stress signaling pathways, we exposed neuroblastoma cells overexpressing ERdj5 to ER stress inducers. ERdj5 promoted apoptosis in tunicamycin, thapsigargin, and bortezomib-treated cells. To provide further evidence that ERdj5 induces ER stress-regulated apoptosis, we targeted Bcl-2 to ER of ERdj5-overexpressing cells. Targeting the Bcl-2 to ER prevented the apoptosis induced by ER stress inducers but not by non-ER stress apoptotic stimuli, suggesting induction of ER stress-regulated apoptosis by ERdj5. ERdj5 enhanced apoptosis by abolishing the ER stress-induced phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) and the subsequent translational repression. ERdj5 was found to inhibit the eIF2alpha phosphorylation under ER stress through inactivating the pancreatic endoplasmic reticulum kinase. The compromised integrated stress response observed in ERdj5-overexpressing ER-stressed cells due to repressed eIF2alpha phosphorylation correlated with impaired neuroblastoma cell resistance under ER stress. These results demonstrate that ERdj5 decreases neuroblastoma cell survival by down-regulating the UPR, raising the possibility that this protein could be a target for anti-tumor approaches.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6282-90
pubmed:meshHeading
pubmed-meshheading:19122239-Apoptosis, pubmed-meshheading:19122239-Cell Line, Tumor, pubmed-meshheading:19122239-Cell Survival, pubmed-meshheading:19122239-Endoplasmic Reticulum, pubmed-meshheading:19122239-Eukaryotic Initiation Factor-2, pubmed-meshheading:19122239-HSP40 Heat-Shock Proteins, pubmed-meshheading:19122239-Heat-Shock Proteins, pubmed-meshheading:19122239-Humans, pubmed-meshheading:19122239-Molecular Chaperones, pubmed-meshheading:19122239-Neoplasm Proteins, pubmed-meshheading:19122239-Neuroblastoma, pubmed-meshheading:19122239-Phosphorylation, pubmed-meshheading:19122239-Protein Biosynthesis, pubmed-meshheading:19122239-Protein Folding, pubmed-meshheading:19122239-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:19122239-Signal Transduction, pubmed-meshheading:19122239-Stress, Physiological
pubmed:year
2009
pubmed:articleTitle
ERdj5 sensitizes neuroblastoma cells to endoplasmic reticulum stress-induced apoptosis.
pubmed:affiliation
Department of Biosciences and Nutrition, Karolinska Institute, S-14157 Huddinge, Sweden. chrtho@ki.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't