@article{KreckelAnanySiegmundetal.2019,
  author    = {Kreckel, Jennifer and Anany, Mohammed A. and Siegmund, Daniela and Wajant, Harald},
  title     = {TRAF2 controls death receptor-induced caspase-8 processing and facilitates proinflammatory signaling},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  number    = {2024},
  doi       = {10.3389/fimmu.2019.02024},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201822},
  year      = {2019},
  abstract  = {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 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.},
  language  = {en}
}