The Caspase-3 Precursor Has a Cytosolic and Mitochondrial Distribution: Implications for Apoptotic Signaling

The Caspase-3 Precursor Has a Cytosolic and Mitochondrial Distribution: Implications for... 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. Footnotes Address all correspondence to Antony Rosen, Johns Hopkins University School of Medicine, 720 Rutland Ave., Room 1055, Baltimore, MD 21205. Tel.: (410) 955-0139. Fax: (410) 955-0964. E-mail: arosen@welchlink.welch.jhu.edu Abbreviations used in this paper: AIF apoptosis-inducing factor CHAPS 3-(3-cholamidopropyl-dimethyllammonio)-1-propanesulfonate DAPI 4′,6-diamidino-2-phenylindole DFF DNA fragmentation factor ECL enhanced chemiluminescence HUVEC human umbilical vein endothelial cells KGM keratinocyte growth medium KRB Krebs' Ringers buffer PARP poly (ADP-ribose) polymerase Submitted: 18 September 1997 Revision received 22 January 1998 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

The Caspase-3 Precursor Has a Cytosolic and Mitochondrial Distribution: Implications for Apoptotic Signaling

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Publisher
Rockefeller University Press
Copyright
© 1998 Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
D.O.I.
10.1083/jcb.140.6.1485
Publisher site
See Article on Publisher Site

Abstract

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. Footnotes Address all correspondence to Antony Rosen, Johns Hopkins University School of Medicine, 720 Rutland Ave., Room 1055, Baltimore, MD 21205. Tel.: (410) 955-0139. Fax: (410) 955-0964. E-mail: arosen@welchlink.welch.jhu.edu Abbreviations used in this paper: AIF apoptosis-inducing factor CHAPS 3-(3-cholamidopropyl-dimethyllammonio)-1-propanesulfonate DAPI 4′,6-diamidino-2-phenylindole DFF DNA fragmentation factor ECL enhanced chemiluminescence HUVEC human umbilical vein endothelial cells KGM keratinocyte growth medium KRB Krebs' Ringers buffer PARP poly (ADP-ribose) polymerase Submitted: 18 September 1997 Revision received 22 January 1998

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Mar 23, 1998

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