The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling

M Mancini, DW Nicholson, S Roy… - The Journal of cell …, 1998 - rupress.org
M Mancini, DW Nicholson, S Roy, NA Thornberry, EP Peterson, LA Casciola-Rosen…
The Journal of cell biology, 1998rupress.org
Caspase-3–mediated proteolysis is a critical element of the apoptotic process. Recent
studies have demonstrated a central role for mitochondrial proteins (eg, Bcl-2 and
cytochrome c) in the activation of caspase-3, by a process that involves interaction of several
protein molecules. Using antibodies that specifically recognize the precursor form of
caspase-3, we demonstrate that the caspase-3 proenzyme has a mitochondrial and
cytosolic distribution in nonapoptotic cells. The mitochondrial caspase-3 precursor is …
Caspase-3–mediated proteolysis is a critical element of the apoptotic process. Recent studies have demonstrated a central role for mitochondrial proteins (e.g., Bcl-2 and cytochrome c) in the activation of caspase-3, by a process that involves interaction of several protein molecules. Using antibodies that specifically recognize the precursor form of caspase-3, we demonstrate that the caspase-3 proenzyme has a mitochondrial and cytosolic distribution in nonapoptotic cells. The mitochondrial caspase-3 precursor is contained in the intermembrane space. Delivery of a variety of apoptotic stimuli is accompanied by loss of mitochondrial caspase-3 precursor staining and appearance of caspase-3 proteolytic activity. We propose that the mitochondrial subpopulation of caspase-3 precursor molecules is coupled to a distinct subset of apoptotic signaling pathways that are Bcl-2 sensitive and that are transduced through multiple mitochondrion-specific protein interactions.
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