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Updated: Aug 10, 2026

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

CD95-induced JNK activation signals are transmitted by the death-inducing signaling complex (DISC), but not by Daxx

T G Hofmann1, A Möller, S P Hehner

  • 1Division of Immunohistochemistry, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

International Journal of Cancer
|June 19, 2001
PubMed

Insights

CD95-mediated JNK activation requires caspases, caspase-8, and FADD. JNK activation is not essential for CD95-mediated cell death, indicating distinct pathways for apoptosis signaling.

Area of Science:

  • Cellular signaling pathways
  • Apoptosis and cell death mechanisms
  • Immunology and molecular biology

Background:

  • The CD95 (APO-1/Fas) receptor plays a critical role in initiating apoptosis.
  • Understanding the downstream signaling cascades, including JNK activation, is crucial for comprehending CD95-mediated cellular responses.
  • The interplay between caspase activation and JNK pathways in CD95 signaling requires further elucidation.

Purpose of the Study:

  • To investigate the specific pathways involved in CD95-mediated JNK activation.
  • To determine the physiological relevance of JNK activation in CD95-induced apoptosis.
  • To delineate the roles of key signaling proteins, such as caspases, FADD, ASK1, and Daxx, in these processes.

Main Methods:

  • Utilized various cell lines with specific protein deficiencies or dominant-negative mutations.
  • Employed caspase inhibitors (zVAD-fmk, CrmA) to assess caspase dependency.
  • Analyzed JNK activation and apoptosis kinetics following CD95 ligation.

Main Results:

  • CD95-mediated JNK activation was strictly dependent on caspase activation.
  • Caspase-8 and FADD were essential for transmitting the CD95-induced JNK signal.
  • ASK1 significantly contributed to the kinetics of caspase, JNK, and apoptosis activation.
  • Impaired apoptosis with Daxx deficiency did not affect JNK signaling.
  • JNK activation was dispensable for CD95-mediated cell killing, despite its inhibition by dominant-negative MKK4/MKK7.

Conclusions:

  • CD95-mediated JNK activation is a caspase-dependent process requiring DISC proteins like caspase-8 and FADD.
  • While ASK1 influences the kinetics, JNK activation is not a prerequisite for CD95-induced apoptosis execution.
  • Distinct signaling branches likely mediate CD95-induced apoptosis and JNK activation.

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