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Updated: Oct 13, 2026

Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell
14:09

Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell

Published on: August 4, 2015

FADD is required for multiple signaling events downstream of the receptor Fas

P Juo1, M S Woo, C J Kuo

  • 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|January 5, 2000
PubMed

Insights

Fas-associated death domain (FADD) is crucial for Fas-induced apoptosis. Mutants lacking FADD resist Fas-mediated cell death, highlighting FADD's essential role in this critical signaling pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • The Fas receptor (also known as CD95 or APO-1) plays a key role in initiating apoptosis, a programmed cell death process.
  • Understanding the molecular machinery downstream of Fas is critical for comprehending immune regulation and disease pathogenesis.

Purpose of the Study:

  • To identify essential adaptor proteins in the Fas-induced apoptotic signaling pathway.
  • To elucidate the specific functions of FADD in mediating Fas-triggered cellular responses.

Main Methods:

  • Chemical mutagenesis of Jurkat T lymphocytes to generate apoptosis-resistant clones.
  • Immunoblot analysis to assess FADD expression levels.
  • Complementation assays using wild-type FADD to restore apoptosis.
  • Analysis of caspase activation and substrate cleavage downstream of Fas.

Main Results:

  • Five distinct cell lines with mutations in the Fas-associated death domain (FADD) were isolated.
  • These FADD-deficient cell lines exhibited complete resistance to Fas-induced apoptosis.
  • Restoration of FADD expression rescued Fas-mediated apoptosis.
  • Activation of caspases (caspase-2, -3, -7, -8) and cleavage of substrates (BID, PKCdelta, PARP) were abolished in FADD mutants.
  • Fas-induced activation of stress kinases (p38, JNK) and ceramide generation were also blocked.

Conclusions:

  • Fas-associated death domain (FADD) is indispensable for multiple signaling events downstream of Fas receptor activation.
  • FADD acts as a central adaptor protein, integrating signals required for initiating apoptosis and other cellular responses.
  • Targeting FADD or its interactions may offer therapeutic strategies for modulating apoptosis in various diseases.

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