A new caspase-8 isoform caspase-8s increased sensitivity to apoptosis in Jurkat cells.
Caspase-8 is a key initiator of death receptor-induced apoptosis. Here we report a novel short isoform of caspase-8 (caspase-8s), which encodes the first (Death Effector Domain) DED and part of the second DED, missing the C-terminal caspase domain. In vivo binding assays showed that transfected caspase-8s bound to (Fas-associated death domain protein) FADD, the adaptor protein in (death-induced signal complex) DISC. To investigate the potential effects of caspase-8s on cell apoptosis, Jurkat cells were stably transfected with caspase-8s. Overexpression of caspase-8s increased sensitivity to the apoptotic stimuli, Fas-agonistic antibody CH11. These results suggest that caspase-8s may act as a promoter of apoptosis through binding to FADD and is involved in the regulation of apoptosis. In addition, the results also indicate that the first DED was an important structure mediating combination between caspase-8 and FADD.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Zhifang
Z
Xu
Kejing
K
Tang
Min
M
Wang
Qing
Q
Rao
Bolin
B
Liu
Jianxiang
J
Wang
D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015153:Blotting, Western; D053181:Caspase 8 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002999:Clone Cells; D053938:DNA Fragmentation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D019014:fas Receptor / Q000819:agonists / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D018076:DNA, Complementary; C491901:FAS protein, human; D053200:Fas-Associated Death Domain Protein; D007527:Isoenzymes; D012333:RNA, Messenger; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8