Caspases 3 and 7: key mediators of mitochondrial events of apoptosis.
The current model of apoptosis holds that upstream signals lead to activation of downstream effector caspases. We generated mice deficient in the two effectors, caspase 3 and caspase 7, which died immediately after birth with defects in cardiac development. Fibroblasts lacking both enzymes were highly resistant to both mitochondrial and death receptor-mediated apoptosis, displayed preservation of mitochondrial membrane potential, and had defective nuclear translocation of apoptosis-inducing factor (AIF). Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis.
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Saquib A
SA
Lakhani
Ali
A
Masud
Keisuke
K
Kuida
George A
GA
Porter
Carmen J
CJ
Booth
Wajahat Z
WZ
Mehal
Irteza
I
Inayat
Richard A
RA
Flavell
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000172:deficiency / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology; D010539:Permeability; D013601:T-Lymphocytes / Q000166:cytology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051033:Apoptosis Inducing Factor; C494830:AIFM1 protein, mouse; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases