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Updated: Jul 16, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

FLASH meets nuclear bodies: CD95 receptor signals via a nuclear pathway

Eva Krieghoff1, Kristijana Milovic-Holm, Thomas G Hofmann

  • 1Research Group Cellular Senescence, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

Cell Cycle (Georgetown, Tex.)
|March 23, 2007
PubMed

Insights

FLICE-associated huge protein (FLASH) moves from the nucleus to mitochondria upon CD95 receptor activation. This nuclear-to-mitochondrial translocation of FLASH is crucial for initiating caspase-8 activation and apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • The CD95 receptor initiates apoptosis through the death-inducing signaling complex (DISC), activating caspase-8.
  • Type II cells typically require a mitochondrial amplification pathway for CD95-induced apoptosis.
  • FLICE-associated huge protein (FLASH) is a caspase-8 binding protein with known roles in DISC assembly and cell cycle regulation.

Purpose of the Study:

  • To reconcile conflicting data on FLASH localization and function in apoptosis.
  • To investigate the role of FLASH in CD95-mediated apoptosis signaling.
  • To explore the nuclear-mitochondrial trafficking of FLASH.

Main Methods:

  • Immunofluorescence microscopy to track FLASH localization.
  • Co-immunoprecipitation to identify protein interactions.
  • Western blotting to assess protein activation.

Main Results:

  • FLASH was identified as a binding partner of Sp100 within PML nuclear bodies.
  • Upon CD95 activation, FLASH translocates from the nucleus to mitochondria.
  • This nuclear-to-mitochondrial movement of FLASH facilitates caspase-8 activation.

Conclusions:

  • FLASH plays a dual role, residing in the nucleus and translocating to mitochondria upon CD95 stimulation.
  • CD95 signaling may involve a nuclear pathway preceding mitochondrial activation.
  • These findings clarify FLASH's function in apoptosis and suggest novel signaling mechanisms.

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