title: The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling.
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.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: D W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: N A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: E P
authors.initials: EP
authors.lastname: Peterson
authors.forename: L A
authors.initials: LA
authors.lastname: Casciola-Rosen
authors.forename: A
authors.initials: A
authors.lastname: Rosen
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D007694:Killer Cells, Natural / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D007938:Leukemia; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D011498:Protein Precursors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases