ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells
dc.contributor.author | Hagenlocher, Cathrin | |
dc.contributor.author | Siebert, Robin | |
dc.contributor.author | Taschke, Bruno | |
dc.contributor.author | Wieske, Senait | |
dc.contributor.author | Hausser, Angelika | |
dc.contributor.author | Rehm, Markus | |
dc.date.accessioned | 2025-04-28T09:56:45Z | |
dc.date.issued | 2022 | |
dc.date.updated | 2024-11-26T08:17:36Z | |
dc.description.abstract | Prolonged 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.sponsorship | Projekt DEAL | |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft (German Research Foundation) | |
dc.description.sponsorship | European Union’s Horizon 2020 research and innovation program | |
dc.identifier.issn | 2058-7716 | |
dc.identifier.other | 1927182921 | |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-162950 | de |
dc.identifier.uri | https://elib.uni-stuttgart.de/handle/11682/16295 | |
dc.identifier.uri | https://doi.org/10.18419/opus-16276 | |
dc.language.iso | en | |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/766069 | |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/859962 | |
dc.relation.uri | doi:10.1038/s41420-022-00830-y | |
dc.rights | CC BY | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject.ddc | 570 | |
dc.title | ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells | en |
dc.type | article | |
dc.type.version | publishedVersion | |
ubs.fakultaet | Energie-, Verfahrens- und Biotechnik | |
ubs.fakultaet | Fakultäts- und hochschulübergreifende Einrichtungen | |
ubs.institut | Institut für Zellbiologie und Immunologie | |
ubs.institut | Stuttgart Research Center Systems Biology (SRCSB) | |
ubs.publikation.seiten | 9 | |
ubs.publikation.source | Cell death discovery 8 (2022), No. 34 | |
ubs.publikation.typ | Zeitschriftenartikel |