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Ceramide phosphoethanolamine synthase SMSr is a target of caspase-6 during apoptotic cell death

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https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018010516506
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dc.creatorCabukusta, Birol-
dc.creatorNettebrock, Niclas T.-
dc.creatorKol, Matthijs-
dc.creatorHilderink, Angelika-
dc.creatorTafesse, Fikadu G.-
dc.creatorHolthuis, Joost C. M.-
dc.date.accessioned2018-01-05T11:38:09Z-
dc.date.available2018-01-05T11:38:09Z-
dc.date.issued2018-01-05T11:38:09Z-
dc.identifier.citationBioscience Reports 37(4) 2017-
dc.identifier.urihttps://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018010516506-
dc.description.abstractCeramides are essential precursors of sphingolipids with a dual role as mediators of apoptotic cell death. Previous work revealed that the ER-resident ceramide phosphoethanolamine (CPE) synthase SMSr/SAMD8 is a suppressor of ceramide-mediated apoptosis in cultured cells. Anti-apoptotic activity of SMSr requires a catalytically active enzyme but also relies on the enzyme’s N-terminal sterile α-motif or SAM domain. Here, we demonstrate that SMSr itself is a target of the apoptotic machinery. Treatment of cells with staurosporine or the death receptor ligand FasL triggers caspase-mediated cleavage of SMSr at a conserved aspartate located downstream of the enzyme’s SAM domain and upstream of its first membrane span. Taking advantage of reconstitution experiments with SMSr produced in a cell-free expression system, specific caspase-inhibitors and gene silencing approaches, we show that SMSr is a novel and specific substrate of caspase-6, a non-conventional effector caspase implicated in Huntington’s and Alzheimer’s diseases. Our findings underscore a role of SMSr as negative regulator of ceramide-induced cell death and, in view of a prominent expression of the enzyme in brain, raise questions regarding its potential involvement in neurodegenerative disorders.eng
dc.relationhttp://www.bioscirep.org/content/37/4/BSR20170867-
dc.rightsNamensnennung 4.0 International-
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/-
dc.subjectaptoptosiseng
dc.subjectcaspaseseng
dc.subjectmembrane biochemistryeng
dc.subjectsphingolipidseng
dc.subject.ddc570 - Biowissenschaften, Biologie-
dc.titleCeramide phosphoethanolamine synthase SMSr is a target of caspase-6 during apoptotic cell deatheng
dc.typeEinzelbeitrag in einer wissenschaftlichen Zeitschrift [article]ger
dc.identifier.doi10.1042/BSR20170867-
vCard.ORGFB5-
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Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons