A Novel Single Amino Acid Deletion Caspase-8 Mutant in Cancer Cells That Lost Proapoptotic Activity

Caspase-8 is an important initiation caspase that activates the caspase cascade during death receptor-mediated apoptosis. We here report a novel caspase-8 mutant with a naturally occurring deletion of leucine 62 (Delta Leu62casp-8). Delta Leu62casp-8 has a shorter half-life than its wild-type counterpart. Unlike wild-type caspase-8, Delta Leu62casp-8 failed to interact with wild-type caspase-8 or with the adaptor protein FADD. Delta Leu62casp-8 lost its proapoptotic activity in mammalian cells. The leucine 62 therefore is critical for caspase-8 function, and the mutation may be one of the mechanisms through which some types of cancer cells escape from programmed cell death.