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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the

F C Kischkel1, S Hellbardt, I Behrmann

  • 1Tumor Immunology Program, German Cancer Center, Heidelberg, Germany.

The EMBO Journal
|November 15, 1995
PubMed

Insights

Researchers identified four key proteins (CAP1-4) that associate with the APO-1 receptor, mediating programmed cell death (apoptosis). These findings reveal crucial intracellular signaling molecules involved in APO-1-induced apoptosis.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • APO-1 (Fas/CD95) is a tumor necrosis factor receptor superfamily member that triggers apoptosis upon oligomerization.
  • Understanding the intracellular signaling pathways activated by APO-1 is crucial for comprehending apoptosis regulation.

Purpose of the Study:

  • To identify intracellular signaling molecules that couple to the oligomerized APO-1 receptor.
  • To characterize the proteins associated with APO-1 during apoptosis induction.

Main Methods:

  • Immunoprecipitation of APO-1-associated proteins (CAP) from human leukemic T cell line HUT78 and lymphoblastoid B cell line SKW6.4.
  • Analysis of CAP association with aggregated versus monomeric APO-1, and with mutated or truncated APO-1 variants.
  • Identification of CAP1 and CAP2 as serine phosphorylated MORT1/FADD.

Main Results:

  • Four CAPs (CAP1-4) were identified and found to associate specifically with aggregated, signaling APO-1.
  • CAP association was dependent on the intact APO-1 cytoplasmic tail and specific amino acid sequences.
  • CAP1 and CAP2 were identified as serine phosphorylated MORT1/FADD, a known apoptosis mediator.

Conclusions:

  • CAP1-4 are likely the in vivo apoptosis-transducing molecules for APO-1.
  • These findings elucidate key components of the APO-1-mediated apoptotic signaling pathway.

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