Alternative Fas-mediated cell death pathway is dependent on the different cleavage patterns of procaspase-8.
It has been reported that mitochondria-independent or mitochondria-dependent (type I/II) Fas signaling pathways in leukemia cells depend on the amount of active caspase-8. However, Bid molecules, which could not be cleaved in type I cells, could be effectively cleaved by recombinant active caspase-8 in vitro. The cleavage of recombinant Bid by recombinant active caspase-8 could be blocked by anti-p10 and anti-p18 specific antibodies. Fas receptors could be similarly internalized into cytoplasm in type I and type II cells. Interestingly, p10 subunit of active caspase-8 could be detected in both type I and II cells, while p18 subunit of active caspase-8 could be detected only in type II cells but not in type I cells. These results demonstrated that p18 subunit was necessary for Bid cleavage and the mitochondria pathway might be dependent on the release of p18 subunit from active caspase-8.
Li
Yufeng
Y
Department of Pediatric and Developmental Science, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
Qi
Lei
L
Iwao
Atsushi
A
Kihira
Kentaro
K
Dida
Francis
F
Song
Zhenhu
Z
Azuma
Eiichi
E
Komada
Yoshihiro
Y
D000906:Antibodies / Q000494:pharmacology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053181:Caspase 8 / Q000737:chemistry / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
D000906:Antibodies; D051023:BH3 Interacting Domain Death Agonist Protein; C491901:FAS protein, human; D021122:Protein Subunits; D011994:Recombinant Proteins; D019014:fas Receptor; D053181:Caspase 8