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.
Liu
Bolin
B
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Peng
Dean
D
Lu
Yang
Y
Jin
Weidong
W
Fan
Zhen
Z
D000596:Amino Acids / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
D000596:Amino Acids; D017931:DNA Primers; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases