Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell death and differentiation, 2005-01, Vol.12 (1), p.25-37

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 lpr(cg) 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.