Activation of Membrane-Associated Procaspase-3 Is Regulated by Bcl-2

The mechanism by which membrane-bound Bcl-2 inhibits the activation of cytoplasmic procaspases is unknown. Here we characterize an intracellular, membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2. Heavy membranes isolated from control cells contained a spontaneously ac...

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Bibliographic Details
Published in:The Journal of cell biology 1999-03, Vol.144 (5), p.915-926
Main Authors: Krebs, Joseph F., Armstrong, Robert C., Srinivasan, Anu, Aja, Teresa, Wong, Angela M., Aboy, Aileen, Sayers, Rob, Pham, Bryan, Vu, Tam, Hoang, Kim, Karanewsky, Donald S., Leist, Christian, Schmitz, Albert, Wu, Joe C., Tomaselli, Kevin J., Fritz, Lawrence C.
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Caspase 3
Caspase Inhibitors
Caspases - metabolism
Cell Line
Cell lines
Cells
Cellular biology
Coumarins - metabolism
Cytochrome c Group - pharmacology
Cytochromes
Enzyme Activation
Enzyme Precursors - antagonists & inhibitors
Enzyme Precursors - metabolism
Enzymes
Fluorescence
Humans
Hydrolysis
Membrane Proteins - metabolism
Membranes
Oligopeptides - metabolism
P branes
Proto-Oncogene Proteins c-bcl-2 - metabolism
Regular
String theory
Subcellular Fractions - metabolism
T lymphocytes
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Summary:The mechanism by which membrane-bound Bcl-2 inhibits the activation of cytoplasmic procaspases is unknown. Here we characterize an intracellular, membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2. Heavy membranes isolated from control cells contained a spontaneously activatable caspase-3 zymogen. In contrast, in Bcl-2 overexpressing cells, although the caspase-3 zymogen was still associated with heavy membranes, its spontaneous activation was blocked. However, Bcl-2 expression had little effect on the levels of cytoplasmic caspase activity in unstimulated cells. Furthermore, the membrane-associated caspase-3 differed from cytosolic caspase-3 in its responsiveness to activation by exogenous cytochrome c. Our results demonstrate that intracellular membranes can generate active caspase-3 by a Bcl-2-inhibitable mechanism, and that control of caspase activation in membranes is distinct from that observed in the cytoplasm. These data suggest that Bcl-2 may control cytoplasmic events in part by blocking the activation of membrane-associated procaspases.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.144.5.915