TY - JOUR AU1 - Mancini, Marie AU2 - Nicholson, Donald W. AU3 - Roy, Sophie AU4 - Thornberry, Nancy A. AU5 - Peterson, Erin P. AU6 - Casciola-Rosen, Livia A. AU7 - Rosen, Antony 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. 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 TI - The Caspase-3 Precursor Has a Cytosolic and Mitochondrial Distribution: Implications for Apoptotic Signaling JF - The Journal of Cell Biology DO - 10.1083/jcb.140.6.1485 DA - 1998-03-23 UR - https://www.deepdyve.com/lp/rockefeller-university-press/the-caspase-3-precursor-has-a-cytosolic-and-mitochondrial-distribution-FVwaY4vpQe SP - 1485 VL - 140 IS - 6 DP - DeepDyve ER -