CD95 apoptosis resistance in certain cells can be overcome by noncanonical activation of caspase-8

B. C. Barnhart, E. M. Pietras, A. Algeciras-Schimnich, L. Salmena, K. Sayama, R. Hakem, M. E. Peter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


CD95 apoptosis resistance of tumor cells is often acquired through mutations in the death domain (DD) of one of the CD95 alleles. Furthermore, Type I cancer cells are resistant to induction of apoptosis by soluble CD95 ligand (CD95L), which does not induce efficient formation of the death-inducing signaling complex (DISC). Here, we report that tumor cells expressing a CD95 allele that lacks a functional DD, splenocytes from heterozygous Iprcg mice, which express one mutated CD95 allele, and Type I tumor cells stimulated with soluble CD95L can all die through CD95 when protein synthesis or nuclear factor kappa B is inhibited. This noncanonical form of CD95-mediated apoptosis is dependent on the enzymatic activity of procaspase-8 but does not involve fully processed active caspase-8 subunits. Our data suggest that it is possible to overcome the CD95 apoptosis resistance of many tumor cells that do not efficiently form a DISC through noncanonical activation of the caspase-8 proenzyme.

Original languageEnglish (US)
Pages (from-to)25-37
Number of pages13
JournalCell Death and Differentiation
Issue number1
StatePublished - Jan 2005


  • Apoptosis
  • CD95
  • Caspase-8
  • Death domain
  • NF-kappaB
  • Tumor cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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