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Updated: Jul 17, 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 links the CD95 signaling pathway to the cell nucleus and nuclear bodies

Kristijana Milovic-Holm1, Eva Krieghoff, Kirsten Jensen

  • 1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.

The EMBO Journal
|January 25, 2007
PubMed

Insights

FLICE-associated huge protein (FLASH) moves from the nucleus to mitochondria upon CD95 activation, regulating apoptosis. This nuclear-to-cytoplasmic translocation of FLASH is crucial for CD95-induced cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Research

Background:

  • FLICE-associated huge protein (FLASH) is implicated in CD95-mediated apoptosis.
  • Caspase-8 activation at the death-inducing signaling complex is critical for apoptosis.
  • The role of FLASH's subcellular localization in apoptosis signaling is not fully understood.

Purpose of the Study:

  • To investigate the role of FLASH's nucleo-cytoplasmic translocation in CD95-induced apoptosis.
  • To elucidate the mechanisms regulating FLASH localization upon CD95 activation.
  • To identify factors influencing FLASH-mediated apoptosis.

Main Methods:

  • Immunofluorescence microscopy to track FLASH localization.
  • RNA interference to downregulate FLASH expression.
  • Caspase activation assays.
  • Co-immunoprecipitation to study protein interactions.
  • Western blotting to assess protein levels.

Main Results:

  • FLASH interacts with Sp100 and resides in nuclear bodies (NBs).
  • CD95 activation induces FLASH translocation from NBs to the cytoplasm and mitochondria.
  • This translocation requires caspase activation and Crm1-dependent nuclear export.
  • FLASH downregulation or inhibition of translocation reduces CD95-induced apoptosis.
  • Adenoviral E1B19K inhibits apoptosis by trapping FLASH and procaspase-8 at mitochondria.
  • Sp100 knockdown enhances apoptosis by increasing FLASH translocation.

Conclusions:

  • CD95 signaling involves a novel nuclear pathway mediated by FLASH nucleo-cytoplasmic translocation.
  • FLASH shuttling between the nucleus and mitochondria is a key regulatory step in CD95-induced apoptosis.
  • Sp100 and E1B19K modulate apoptosis by affecting FLASH localization and function.

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