Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Two CD95 (APO-1/Fas) signaling pathways

C Scaffidi1, S Fulda, A Srinivasan

  • 1Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

The EMBO Journal
|May 2, 1998
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Integrating multimodal prehabilitation into enhanced recovery after surgery programs (MPhERAS) for elderly patients: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Techniques in coloproctology·2025
Same author

<i>Meso</i>-Modified Porphyrinoids: Stimuli-Driven Conformational Plasticity, Modulation of π-Conjugation, and Bis-Rh(I) Complexation.

Inorganic chemistry·2025
Same author

Nonalternant Acenaphthylene-Fused Carbaporphyrins: Topological Modulation of π-Delocalization, (Anti)aromaticity, and B<sup>III</sup> Coordination.

Organic letters·2025
Same author

Siamese Twin Homocarbaporphyrin Dimer: Nonplanar Architecture, Localized Conjugation and Bis-B<sup>III</sup> Complex.

Chemistry, an Asian journal·2025
Same author

<i>E</i>-Stilbene-Imprinted Cyclic Diphyrin and Its B<sup>III</sup> Complex.

Organic letters·2025
Same author

Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation.

Frontiers in molecular neuroscience·2025
Same journal

Scalable phosphotyrosine enrichment with SH2 superbinder enables deep profiling of EGF responses.

The EMBO journal·2026
Same journal

Essential nucleus-apical pole linkage maintains division fidelity during Plasmodium progeny formation.

The EMBO journal·2026
Same journal

From cell atlases to mechanisms: bridging scRNA-seq discovery with in vivo genetics.

The EMBO journal·2026
Same journal

Mitochondrial calcium regulates lipid metabolism by modulating tethering of mitochondria to lipid droplets.

The EMBO journal·2026
Same journal

Chromosome condensation mechanically primes the nucleus for mitosis.

The EMBO journal·2026
Same journal

NDR kinase SAX-1 controls dendrite branch-specific elimination during neuronal remodeling in C. elegans.

The EMBO journal·2026
See all related articles

Two CD95 (APO-1/Fas) signaling pathways determine cell death. Type I cells rapidly activate caspases via the DISC for mitochondria-independent apoptosis, while type II cells show delayed caspase activation after mitochondrial events.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Research

Background:

  • The CD95 (APO-1/Fas) receptor plays a critical role in initiating programmed cell death.
  • Distinct signaling pathways downstream of CD95 can lead to varying apoptotic outcomes.
  • Understanding these pathways is crucial for developing targeted therapies for diseases involving apoptosis.

Purpose of the Study:

  • To elucidate the distinct CD95 signaling pathways in different cell types.
  • To investigate the role of caspases and mitochondrial integrity in CD95-mediated apoptosis.
  • To determine the factors governing the choice between mitochondria-dependent and -independent apoptosis.

Main Methods:

  • Utilized cell lines with distinct CD95 signaling characteristics (Type I and Type II).

Related Experiment Videos

  • Analyzed caspase-8 and caspase-3 activation kinetics upon CD95 receptor engagement.
  • Assessed mitochondrial transmembrane potential (ΔPsim) and blocked apoptosis using Bcl-2 or Bcl-xL overexpression.
  • Investigated the impact of caspase-3 overexpression in resistant cell lines.

    • Main Results:

    • Identified two CD95 signaling pathways: Type I (rapid caspase activation at DISC) and Type II (delayed caspase activation post-mitochondrial events).
    • Mitochondrial apoptogenic activities were blocked by Bcl-2/Bcl-xL in both cell types.
    • Bcl-2/Bcl-xL overexpression inhibited apoptosis in Type II but not Type I cells.
    • Overexpression of caspase-3 converted resistant cells into Type I cells, bypassing Bcl-xL inhibition.

    Conclusions:

    • The amount of active caspase-8 generated at the DISC dictates the apoptosis pathway (mitochondria-independent in Type I, dependent in Type II) in the presence of caspase-3.
    • Cellular context and caspase-3 levels are critical determinants of CD95-mediated apoptosis kinetics and pathway choice.
    • These findings provide insights into the regulation of apoptosis and potential therapeutic strategies.