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The Journal of cell biology
Mar 23, 1998;140 (6): 1485-95.

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

M Mancini, D W Nicholson, S Roy, N A Thornberry, E P Peterson, L A Casciola-Rosen, A Rosen
Author Information
  1. M Mancini: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
PMID: 9508780 DOI: 10.1083/jcb.140.6.1485

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.

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Grants

  1. R01 AR044684/NIAMS NIH HHS
  2. K12DK01298/NIDDK NIH HHS
  3. T32 AI007247/NIAID NIH HHS
  4. 5T32-AI07247/NIAID NIH HHS
  5. AR44684/NIAMS NIH HHS

MeSH Term

Apoptosis
Caspase 3
Caspases
Cysteine Endopeptidases
Cytosol
Humans
Keratinocytes
Killer Cells, Natural
Leukemia
Microscopy, Electron
Mitochondria
Protein Precursors
Signal Transduction
Tumor Cells, Cultured

Chemicals

Protein Precursors
CASP3 protein, human
Caspase 3
Caspases
Cysteine Endopeptidases
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
Article has an altmetric score of 3

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