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Title: Characterization of a serine protease-mediated cell death program activated in human leukemia cells

Abstract

Tightly controlled proteolysis is a defining feature of apoptosis and caspases are critical in this regard. Significant roles for non-caspase proteases in cell death have been highlighted. Staurosporine causes a rapid induction of apoptosis in virtually all mammalian cell types. Numerous studies demonstrate that staurosporine can activate cell death under caspase-inhibiting circumstances. The aim of this study was to investigate the proteolytic mechanisms responsible for cell death under these conditions. To that end, we show that inhibitors of serine proteases can delay cell death in one such system. Furthermore, through profiling of proteolytic activation, we demonstrate, for the first time, that staurosporine activates a chymotrypsin-like serine protease-dependent cell death in HL-60 cells independently, but in parallel with the caspase controlled systems. Features of the serine protease-mediated system include cell shrinkage and apoptotic morphology, regulation of caspase-3, altered nuclear morphology, generation of an endonuclease and DNA degradation. We also demonstrate a staurosporine-induced activation of a putative 16 kDa chymotrypsin-like protein during apoptosis.

Authors:
 [1];  [1];  [2];  [3];  [4]
  1. National Centre for Biomedical Engineering Science and Department of Biochemistry, National University of Ireland, Galway (Ireland)
  2. Institut de Recherches Biomedicales des Cordeliers, INSERM U 598, 15, Rue de l'Ecole de Medecine 75006 Paris (France)
  3. Immunochemistry Technologies LLC., 9401 James Avenue South Suite 155, Bloomington, MN 55431 (United States)
  4. National Centre for Biomedical Engineering Science and Department of Biochemistry, National University of Ireland, Galway (Ireland). E-mail: catherine.stenson@nuigalway.ie
Publication Date:
OSTI Identifier:
20775325
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 312; Journal Issue: 1; Other Information: DOI: 10.1016/j.yexcr.2005.10.003; PII: S0014-4827(05)00456-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CHYMOTRYPSIN; DNA; LEUKEMIA; MORPHOLOGY; PROTEOLYSIS; SERINE

Citation Formats

O'Connell, A.R., Holohan, C., Torriglia, A., Lee, B.F., and Stenson-Cox, C. Characterization of a serine protease-mediated cell death program activated in human leukemia cells. United States: N. p., 2006. Web. doi:10.1016/j.yexcr.2005.10.003.
O'Connell, A.R., Holohan, C., Torriglia, A., Lee, B.F., & Stenson-Cox, C. Characterization of a serine protease-mediated cell death program activated in human leukemia cells. United States. doi:10.1016/j.yexcr.2005.10.003.
O'Connell, A.R., Holohan, C., Torriglia, A., Lee, B.F., and Stenson-Cox, C. Sun . "Characterization of a serine protease-mediated cell death program activated in human leukemia cells". United States. doi:10.1016/j.yexcr.2005.10.003.
@article{osti_20775325,
title = {Characterization of a serine protease-mediated cell death program activated in human leukemia cells},
author = {O'Connell, A.R. and Holohan, C. and Torriglia, A. and Lee, B.F. and Stenson-Cox, C.},
abstractNote = {Tightly controlled proteolysis is a defining feature of apoptosis and caspases are critical in this regard. Significant roles for non-caspase proteases in cell death have been highlighted. Staurosporine causes a rapid induction of apoptosis in virtually all mammalian cell types. Numerous studies demonstrate that staurosporine can activate cell death under caspase-inhibiting circumstances. The aim of this study was to investigate the proteolytic mechanisms responsible for cell death under these conditions. To that end, we show that inhibitors of serine proteases can delay cell death in one such system. Furthermore, through profiling of proteolytic activation, we demonstrate, for the first time, that staurosporine activates a chymotrypsin-like serine protease-dependent cell death in HL-60 cells independently, but in parallel with the caspase controlled systems. Features of the serine protease-mediated system include cell shrinkage and apoptotic morphology, regulation of caspase-3, altered nuclear morphology, generation of an endonuclease and DNA degradation. We also demonstrate a staurosporine-induced activation of a putative 16 kDa chymotrypsin-like protein during apoptosis.},
doi = {10.1016/j.yexcr.2005.10.003},
journal = {Experimental Cell Research},
number = 1,
volume = 312,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}