Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR5

Thomas, Lance R.; Bender, Laura; Morgan, Michael J.; Thorburn, Andrew

doi:10.1038/sj.cdd.4401714

Cited by 8 publications

(4 citation statements)

References 14 publications

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“…The fact that the K280A mutant is shown here to reduce the ability of CD95/Fas to induce apoptosis both corroborates the NMR data and provides functional evidence for this residue, and helix a5, in the CD95/ Fas-DD:FADD-DD binding event. Alongside reports that multiple surfaces of FADD-DD are implicated in the interaction with death receptor DD, 18,19 prompting models for the homotypic DD-DD interaction that require more than a single surface of the CD95/Fas-DD, 6,10,20 our results provide both corroboration for, and a platform for further exploration of, the high molecular weight complex that is apparently formed. Precedent for multimeric DD/DD complexes has been set by the determination of the RAIDD-DD/PIDD-DD complex structure in which seven protomers of RAIDD-DD interact with five of PIDD-DD to form the core of the caspase-2 activating PIDDosome complex.…”

supporting

confidence: 70%

Biophysical and cell-based evidence for differential interactions between the death domains of CD95/Fas and FADD

et al. 2007

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supporting

confidence: 70%

Biophysical and cell-based evidence for differential interactions between the death domains of CD95/Fas and FADD

et al. 2007

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“…Decreasing FLIP expression sensitises cells to death ligands. 21 Because we know that TSA sensitises RASF for TRAILinduced apoptosis, we conclude that TSA discloses sensitive sites in the cascade of TRAIL signalling and, thus might represent a new principle for the treatment of RA. Figure 3 Western blot showing expression of p21 Waf1/Cip1 and atubulin by RASF at 19 kDa and 55 kDa.…”

Section: Discussionmentioning

confidence: 76%

Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis

Jüngel

Barešová²,

Ospelt³

et al. 2005

Annals of the Rheumatic Diseases

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Background: Histone acetylation/deacetylation has a critical role in the regulation of transcription by altering the chromatin structure. Objective: To analyse the effect of trichostatin A (TSA), a streptomyces metabolite which specifically inhibits mammalian histone deacetylases, on TRAIL-induced apoptosis of rheumatoid arthritis synovial fibroblasts (RASF). Methods: Apoptotic cells were detected after co-treatment of RASF with TRAIL (200 ng/ml) and TSA (0.5, 1, and 2 mmol/l) by flow cytometry using propidium iodide/annexin-V-FITC staining. Cell proliferation was assessed using the MTS proliferation test. Induction of the cell cycle inhibitor p21Waf/Cip1 by TSA was analysed by western blot. Expression of the TRAIL receptor-2 (DR5) on the cell surface of RASF was analysed by flow cytometry. Levels of soluble TRAIL were measured in synovial fluid of patients with RA and osteoarthritis (OA) by ELISA. Results: Co-treatment of the cells with TSA and TRAIL induced cell death in a synergistic and dose dependent manner, whereas TRAIL and TSA alone had no effect or only a modest effect. RASF express DR5 (TRAIL receptor 2), but treatment of the cells with TSA for 24 hours did not change the expression level of DR5, as it is shown for cancer cells. TSA induced cell cycle arrest in RASF through up regulation of p21 Waf1/Cip1 . Levels of soluble TRAIL were significantly higher in RA than in OA synovial fluids. Conclusion: Because TSA sensitises RASF for TRAIL-induced apoptosis, it is concluded that TSA discloses sensitive sites in the cascade of TRAIL signalling and may represent a new principle for the treatment of RA.

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“…Some parts of this receptor interact with TRAIL (24), whereas FADD binds with its DD at the DD of TNFRSF10b resulting in formation of the death-inducing signaling complex (DISC). Further, it recruits caspase 8 to DISC, engaging the caspase cascade to induce apoptosis (25). It seems that TNFRSF10b is selectively expressed in cancer cells and may induce TRAILinduced apoptosis in cancer cells (26).…”

Section: Discussionmentioning

confidence: 99%

Christia vespertilionis plant extracts as novel antiproliferative agent against human neuroendocrine tumor cells

Hofer

Schwach

Ghaffari-Tabrizi-Wizsy

et al. 2013

Oncology Reports

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Neuroendocrine tumors respond poorly to radiation and conventional chemotherapy, hence surgical removal of the neoplastic tissue is still the most effective way of treatment. In an attempt to find new therapeutic plant extracts of Christia vespertilionis (CV) their antitumor potential in human medullary thyroid carcinoma (MTC) and human small intestinal neuroendocrine tumor (SI-NET) cell lines were tested. Proliferation and viability were analyzed using cell counting and WST-1 assay. Apoptosis was determined by microscopy, luminescence assays for caspases 3/7, and expression studies of apoptosis-related genes. CV extracts showed antiproliferative and proapoptotic effects in all MTC and SI-NET cell lines, whereby high growth inhibition was observed by treatment with the ethylacetate-extracts (CV-45) in tumor cell lines but not in normal human fibroblasts. Furthermore CV-45 treatment resulted in alterations of gene expression of PDCD5, MTDH and TNFRSF10b in MTC as well as in SI-NET cells. The results indicate that Christia vespertilionis could serve as an anticancer therapeutic for treatment of neuroendocrine tumors.

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Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR5

Cited by 8 publications

References 14 publications

Biophysical and cell-based evidence for differential interactions between the death domains of CD95/Fas and FADD

Biophysical and cell-based evidence for differential interactions between the death domains of CD95/Fas and FADD

Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis

Christia vespertilionis plant extracts as novel antiproliferative agent against human neuroendocrine tumor cells

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