Abstract
The p55 tumor necrosis factor (TNF) receptor and the Fas (CD95/APO-1) receptor share an intracellular domain necessary to induce apoptosis, suggesting they utilize common signaling pathways. To define pathways triggered by Fas and TNF-α we utilized human CEM-C7 T-cells. As expected, stimulation of either receptor induced apoptosis and TNF-α-induced signaling included the activation of NF-κB. Surprisingly, Fas-induced signaling also triggered the activation of NF-κB in T cells, yet the kinetics of NF-κB induction by Fas was markedly delayed. NF-κB activation by both pathways was persistent and due to the sequential degradation of IκB-α and IκB-β. However, the kinetics of IκB degradation were different and there were differential effects of protease inhibitors and antioxidants on NF-κB activation. Signaling pathways leading to activation of apoptosis were similarly separable and were also independent of NF-κB activation. Thus, the Fas and TNF receptors utilize distinct signal transduction pathways in T-cells to induce NF-κB and apoptosis.
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Packham, G., Lahti, J., Fee, B. et al. Fas activates NF-κB and induces apoptosis in T-cell lines by signaling pathways distinct from those induced by TNF-α. Cell Death Differ 4, 130–139 (1997). https://doi.org/10.1038/sj.cdd.4400217
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DOI: https://doi.org/10.1038/sj.cdd.4400217
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