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Fas activates NF-kappaB and induces apoptosis in T-cell lines by signaling pathways distinct from those induced by

G Packham1, J M Lahti, B E Fee

  • 1Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Cell Death and Differentiation
|February 1, 1997
PubMed

Insights

Tumor necrosis factor (TNF) and Fas receptors initiate apoptosis via distinct T-cell signaling pathways. While both activate NF-kappaB, Fas signaling shows delayed kinetics, revealing unique signal transduction mechanisms.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • The p55 tumor necrosis factor (TNF) receptor and Fas (CD95/APO-1) receptor share intracellular domains crucial for apoptosis induction.
  • This shared domain suggests potential overlap in their downstream signaling pathways.

Purpose of the Study:

  • To elucidate and differentiate the signaling pathways triggered by Fas and TNF-alpha in human CEM-C7 T-cells.
  • To investigate the role of NF-kappaB activation and IkappaB degradation in Fas and TNF-alpha mediated signaling.

Main Methods:

  • Utilized human CEM-C7 T-cells for experimental analysis.
  • Stimulated cells with Fas and TNF-alpha to observe cellular responses.
  • Analyzed NF-kappaB activation kinetics and IkappaB-alpha/beta degradation.
  • Assessed the impact of protease inhibitors and antioxidants on signaling pathways.

Main Results:

  • Both Fas and TNF-alpha stimulation induced apoptosis in T-cells.
  • TNF-alpha signaling rapidly activated NF-kappaB, while Fas signaling showed a delayed NF-kappaB induction.
  • NF-kappaB activation was sustained by sequential degradation of IkappaB-alpha and IkappaB-beta, with distinct kinetics for each receptor.
  • Apoptosis signaling pathways were separable and independent of NF-kappaB activation.

Conclusions:

  • Fas and TNF receptors employ distinct signal transduction pathways in T-cells.
  • These distinct pathways lead to differential activation of NF-kappaB and apoptosis.
  • The findings highlight the complexity of immune receptor signaling in T-cells.

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