ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells

dc.contributor.authorHagenlocher, Cathrin
dc.contributor.authorSiebert, Robin
dc.contributor.authorTaschke, Bruno
dc.contributor.authorWieske, Senait
dc.contributor.authorHausser, Angelika
dc.contributor.authorRehm, Markus
dc.date.accessioned2025-04-28T09:56:45Z
dc.date.issued2022
dc.date.updated2024-11-26T08:17:36Z
dc.description.abstractProlonged ER stress and the associated unfolded protein response (UPR) can trigger programmed cell death. Studies in cancer cell lines demonstrated that the intracellular accumulation of TRAIL receptor-2 (TRAIL-R2) and the subsequent activation of caspase-8 contribute significantly to apoptosis induction upon ER stress. While this might motivate therapeutic strategies that promote cancer cell death through ER stress-induced caspase-8 activation, it could also support the unwanted demise of non-cancer cells. Here, we therefore investigated if TRAIL-R2 dependent signaling towards apoptosis can be induced in pancreatic β cells, whose loss by prolonged ER stress is associated with the onset of diabetes. Interestingly, we found that elevated ER stress in these cells does not result in TRAIL-R2 transcriptional induction or elevated protein levels, and that the barely detectable expression of TRAIL-R2 is insufficient to allow TRAIL-induced apoptosis to proceed. Overall, this indicates that apoptotic cell death upon ER stress most likely proceeds independent of TRAIL-R2 in pancreatic β cells. Our findings therefore point to differences in ER stress response and death decision-making between cancer cells and pancreatic β cells and also have implications for future targeted treatment strategies that need to differentiate between ER stress susceptibility of cancer cells and pancreatic β cells.en
dc.description.sponsorshipProjekt DEAL
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (German Research Foundation)
dc.description.sponsorshipEuropean Union’s Horizon 2020 research and innovation program
dc.identifier.issn2058-7716
dc.identifier.other1927182921
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-162950de
dc.identifier.urihttps://elib.uni-stuttgart.de/handle/11682/16295
dc.identifier.urihttps://doi.org/10.18419/opus-16276
dc.language.isoen
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/766069
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/859962
dc.relation.uridoi:10.1038/s41420-022-00830-y
dc.rightsCC BY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc570
dc.titleER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cellsen
dc.typearticle
dc.type.versionpublishedVersion
ubs.fakultaetEnergie-, Verfahrens- und Biotechnik
ubs.fakultaetFakultäts- und hochschulübergreifende Einrichtungen
ubs.institutInstitut für Zellbiologie und Immunologie
ubs.institutStuttgart Research Center Systems Biology (SRCSB)
ubs.publikation.seiten9
ubs.publikation.sourceCell death discovery 8 (2022), No. 34
ubs.publikation.typZeitschriftenartikel

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