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Updated: Oct 4, 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

Cleavage of E2F-1-regulating proteins and activation of E2F-1 during CD95-induced death of thymocytes

B Bi1, N K Littlewood, I N Crispe

  • 1Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Immunology
|September 29, 2001
PubMed

Insights

CD95 death receptor signaling cleaves cell cycle regulators, increasing E2F-1 activity. This enhanced E2F-1 drives CD95-induced apoptosis, highlighting the G1/S checkpoint as a key target.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • The CD95 death receptor initiates caspase cascades, leading to the cleavage of intracellular substrates.
  • The precise role of caspase-mediated cleavage of cell cycle control proteins in apoptosis induction remains incompletely understood.

Purpose of the Study:

  • To investigate the significance of CD95-induced cleavage of G1/S checkpoint regulators.
  • To determine the impact of this cleavage on the activity of the transcription factor E2F-1.
  • To elucidate the role of E2F-1 in CD95-mediated apoptosis.

Main Methods:

  • Analysis of CD95-induced cleavage of retinoblastoma protein (pRb) and murine-double-minute-2 (mdm-2).
  • Assessment of E2F-1 protein concentration and DNA-binding activity.
  • Examination of CD95-induced apoptosis in wild-type and E2F-1-deficient thymocytes.

Main Results:

  • CD95-induced cleavage of pRb and mdm-2 correlated with increased E2F-1 protein levels.
  • Enhanced DNA-binding activity to E2F sites was observed following CD95 activation.
  • Thymocytes lacking E2F-1 exhibited reduced susceptibility to CD95-induced apoptosis.

Conclusions:

  • The G1/S checkpoint is a critical target of CD95 signaling pathways.
  • CD95-activated caspases contribute to apoptosis by increasing E2F-1 activity through regulator cleavage.
  • Inappropriate E2F-1 activation is integral to the mechanism of CD95-induced cell death.

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