CD95 apoptosis resistance in certain cells can be overcome by noncanonical activation of caspase-8 |
| |
Authors: | Barnhart B C Pietras E M Algeciras-Schimnich A Salmena L Sayama K Hakem R Peter M E |
| |
Institution: | The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|