liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
ERdj5 sensitizes neuroblastoma cells to endoplasmic reticulum stress-induced apoptosis
Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
Foundation for Biomedical Research, Academy of Athens, Greece.
2009 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 284, no 10, 6282-6290 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2009. Vol. 284, no 10, 6282-6290 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-98718DOI: 10.1074/jbc.M806189200ISI: 000263742700031PubMedID: 19122239OAI: diva2:655543
Available from: 2013-10-11 Created: 2013-10-11 Last updated: 2013-10-18

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Spyrou, Giannis
In the same journal
Journal of Biological Chemistry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 17 hits
ReferencesLink to record
Permanent link

Direct link