Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis

BMC Cell Biology - Tập 14 Số 1 - 2013
Matthew Brentnall1,2, Luis Rodriguez-Menocal3, Rebeka Ladron De Guevara3, Enriqué Cepero3, Lawrence Boise1
1Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, Atlanta, USA
2Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, USA
3Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, USA

Tóm tắt

AbstractBackground

Apoptosis is a form of programmed cell death that is regulated by the Bcl-2 family and caspase family of proteins. The caspase cascade responsible for executing cell death following cytochromecrelease is well described; however the distinct roles of caspases-9, -3 and -7 during this process are not completely defined.

Results

Here we demonstrate several unique functions for each of these caspases during cell death. Specific inhibition of caspase-9 allows for efficient release of cytochromec, but blocks changes in mitochondrial morphology and ROS production. We show that caspase-9 can cleave Bid into tBid at amino acid 59 and that this cleavage of Bid is required for ROS production following serum withdrawal. We also demonstrate that caspase-3-deficient MEFs are less sensitive to intrinsic cell death stimulation, yet have higher ROS production. In contrast, caspase-7-deficient MEFs are not resistance to intrinsic cell death, but remain attached to the ECM.

Conclusions

Taken together, these data suggest that caspase-9 is required for mitochondrial morphological changes and ROS production by cleaving and activating Bid into tBid. After activation by caspase-9, caspase-3 inhibits ROS production and is required for efficient execution of apoptosis, while effector caspase-7 is required for apoptotic cell detachment.

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BMC Cell Biology

Tập 14 Số 1

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