Apoptosis signaling by death receptors

Klaus Schulze-Osthoff*, Davide Ferrari, Marek Los, Sebastian Wesselborg, Marcus E. Peter

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

859 Scopus citations


Death receptors have been recently identified as a subgroup of the TNF- receptor superfamily with a predominant function in induction of apoptosis. The receptors are characterized by an intracellular region, called the death domain, which is required for the transmission of the cytotoxic signal. Currently, five different such death receptors are known including tumor necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF-receptor-related apoptosis-mediated protein (TRAMP) and TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2. The signaling pathways by which these receptors induce apoptosis are rather similar. Ligand binding induces receptor oligomerization, followed by the recruitment of an adaptor protein to the death domain through homophilic interaction. The adaptor protein then binds a proximal caspase, thereby connecting receptor signaling to the apoptotic effector machinery. In addition, further pathways have been linked to death receptor-mediated apoptosis, such as sphingomyelinases, JNK kinases and oxidative stress. These pro-apoptotic signals are counteracted by several mechanisms which inhibit apoptosis at different levels. This review summarizes the current and rapidly expanding knowledge about the biological functions of death receptors and the mechanisms to trigger or to counteract cell death.

Original languageEnglish (US)
Pages (from-to)439-459
Number of pages21
JournalEuropean Journal of Biochemistry
Issue number3
StatePublished - Jun 15 1998


  • Apoptosis
  • Bcl-2
  • CD95 (APO-1/Fas)
  • Caspase
  • Death receptor
  • Inhibitor of apoptosis protein
  • Nuclear factor-κB
  • Tumor-necrosis factor
  • Tumor-necrosis- factor-related apoptosis-inducing ligand
  • Tumor-necrosis-factor-receptor- related apoptosis-mediating protein

ASJC Scopus subject areas

  • Biochemistry


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