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Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.
Journal article

Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.

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  • 1998-02-14
Published in:
  • Nature. - 1998
Animals
Apoptosis
Caspase 3
Caspases
Cell Survival
Cells, Cultured
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors
Cytochrome c Group
DNA Fragmentation
Enzyme Activation
Humans
Mitochondria
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
Rats
Transfection
Tumor Cells, Cultured
bcl-2-Associated X Protein
English Following exposure of cells to stimuli that trigger programmed cell death (apoptosis), cytochrome c is rapidly released from mitochondria into the cytoplasm where it activates proteolytic molecules known as caspases that specifically cleave the amino-acid sequence DEVD and are crucial for the execution of apoptosis. The protein Bcl-2 interferes with this activation of caspases by preventing the release of cytochrome c. Here we study these molecular interactions during apoptosis induced by the protein Bax, a pro-apoptotic homologue of Bcl-2. We show that in cells transiently transfected with bax, Bax localizes to mitochondria and induces the release of cytochrome c, activation of caspase-3, membrane blebbing, nuclear fragmentation, and cell death. Caspase inhibitors do not affect Bax-induced cytochrome c release but block caspase-3 activation and nuclear fragmentation. Unexpectedly, Bcl-2 also fails to prevent Bax-induced cytochrome c release, although it co-localizes with Bax to mitochondria. Cells overexpressing both Bcl-2 and Bax show no signs of caspase activation and survive with significant amounts of cytochrome c in the cytoplasm. These findings indicate that Bcl-2 can interfere with Bax killing downstream of and independently of cytochrome c release.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/136905
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