Deficiency of caspase-3 in MCF7 cells blocks Bax-mediated nuclear fragmentation but not cell death.
Caspase-3 plays a critical role in a proteolytic cascade within the apoptosis signal pathway; this enzyme is commonly activated by numerous death signals and cleaves a variety of important cellular proteins. Using caspase-3-deficient MCF7 cells and clones stably transfected with the caspase-3 gene (MCF7/Casp3), we evaluated the role of caspase-3 in Bax-induced apoptosis. Bax overexpression induced cell death in both parental MCF7 cells and MCF7/Casp3 cells. The introduction of the caspase-3 gene did not change the rate of cell death. Caspase-3-deficient parental MCF7 cells, however, failed to undergo morphological nuclear and DNA fragmentation, whereas MCF7/casp3 cells displayed intact nuclear dismantling and DNA fragmentation. Caspase-3 deficiency, however, did not affect Bax-induced levels of poly(ADP-ribose) polymerase cleavage, caspase-6 activation, and lamin B cleavage. Together, these results suggest that a deficit in caspase-3 is not sufficient to block Bax-induced cell death.
Kagawa
S
S
Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gu
J
J
Honda
T
T
McDonnell
T J
TJ
Swisher
S G
SG
Roth
J A
JA
Fang
B
B
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000502:physiology*; D053938:DNA Fragmentation; D004789:Enzyme Activation; D006801:Humans; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C505514:CASP6 protein, human; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases