TRAF2 controls death receptor-induced caspase-8 processing and facilitates proinflammatory signaling

Please always quote using this URN: urn:nbn:de:bvb:20-opus-201822
  • Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) knockout (KO) cells were generated to investigate the role of TRAF2 in signaling by TNFR1 and the CD95-type death receptors (DRs) TRAILR1/2 and CD95. To prevent negative selection effects arising from the increased cell death sensitivity of TRAF2-deficient cells, cell lines were used for the generation of the TRAF2 KO variants that were protected from DR-induced apoptosis downstream of caspase-8 activation. As already described in the literature, TRAF2 KO cells displayed enhancedTumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) knockout (KO) cells were generated to investigate the role of TRAF2 in signaling by TNFR1 and the CD95-type death receptors (DRs) TRAILR1/2 and CD95. To prevent negative selection effects arising from the increased cell death sensitivity of TRAF2-deficient cells, cell lines were used for the generation of the TRAF2 KO variants that were protected from DR-induced apoptosis downstream of caspase-8 activation. As already described in the literature, TRAF2 KO cells displayed enhanced constitutive alternative NFκB signaling and reduced TNFR1-induced activation of the classical NFκB pathway. There was furthermore a significant but only partial reduction in CD95-type DR-induced upregulation of the proinflammatory NFκB-regulated cytokine interleukin-8 (IL8), which could be reversed by reexpression of TRAF2. In contrast, expression of the TRAF2-related TRAF1 protein failed to functionally restore TRAF2 deficiency. TRAF2 deficiency resulted furthermore in enhanced procaspase-8 processing by DRs, but this surprisingly came along with a reduction in net caspase-8 activity. In sum, our data argue for (i) a non-obligate promoting function of TRAF2 in proinflammatory DR signaling and (ii) a yet unrecognized stabilizing effect of TRAF2 on caspase-8 activity.show moreshow less

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Metadaten
Author: Jennifer Kreckel, Mohammed A. Anany, Daniela Siegmund, Harald Wajant
URN:urn:nbn:de:bvb:20-opus-201822
Document Type:Journal article
Faculties:Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Language:English
Parent Title (English):Frontiers in Immunology
Year of Completion:2019
Volume:10
Issue:2024
Source:Frontiers in Immunology 2019, 10:2024. doi: 10.3389/fimmu.2019.02024
DOI:https://doi.org/10.3389/fimmu.2019.02024
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CD95; TNFR1; TRAF1; TRAF2; TRAILR1; TRAILR2; caspase-8; death receptors
Release Date:2020/03/25
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2019
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International