title: Cell cycle dependency of caspase activation in Fas-induced apoptosis in leukemia cells.
abstract: The relationship between apoptosis and the cell cycle remains unclear. In the present study we have investigated the relationship between cell cycle progression and the activation of caspases (caspase-3 and caspase-8) in Fas (CD95)-mediated apoptosis in asynchronously growing leukemia cells. We found that cells expressing the active form of caspase-3 were cyclin A/B1 and Ki-67 negative but cyclin E positive, whereas expression of the active form of caspase-8 was detected in cyclin A/B1/E-negative and Ki-67-negative cells. In addition, both the activation of caspases and Fas-mediated apoptosis were completely abolished when leukemia cells were arrested in early G1 phase. Using post-sorting western blot analysis, we demonstrated that caspase-3 and caspase-8 were activated in p27-negative cells. These results suggest that caspase-3 would be activated in cells entering into late G1 or early S phase, and caspase-8 would be activated in middle or late G1 phase. The speed of cell cycle progression from G1 to S phase might be influential in the speed of caspase activation and induction of Fas-mediated apoptosis.
authors.affiliation: Department of Pediatrics and Developmental Science, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Francis
authors.initials: F
authors.lastname: Dida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwao
authors.forename: Takao
authors.initials: T
authors.lastname: Deguchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Azuma
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D020169:Caspases / Q000096:biosynthesis*; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D016193:G1 Phase; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000494:pharmacology*
chemical_list: D016213:Cyclins; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases