TY - JOUR
T1 - The caspase-3 precursor has a cytosolic and mitochondrial distribution
T2 - Implications for apoptotic signaling
AU - Mancini, Marie
AU - Nicholson, Donald W.
AU - Roy, Sophie
AU - Thornberry, Nancy A.
AU - Peterson, Erin P.
AU - Casciola-Rosen, Livia A.
AU - Rosen, Antony
PY - 1998/3/23
Y1 - 1998/3/23
N2 - 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.
AB - 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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U2 - 10.1083/jcb.140.6.1485
DO - 10.1083/jcb.140.6.1485
M3 - Article
C2 - 9508780
AN - SCOPUS:0032559799
SN - 0021-9525
VL - 140
SP - 1485
EP - 1495
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -