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.…
Author: | Jennifer Kreckel, Mohammed A. Anany, Daniela Siegmund, Harald Wajant |
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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): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |