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

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 dem...

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Bibliographic Details
Published in:Experimental cell research 2006, Vol.312 (1), p.27-39
Main Authors: O'Connell, A.R., Holohan, C., Torriglia, A., Lee, B.F., Stenson-Cox, C.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
APOPTOSIS
Apoptosis - drug effects
Blotting, Western
Caspase
Caspase 3
Caspase Inhibitors
Caspases - metabolism
Chymases
CHYMOTRYPSIN
DNA
HL-60 cells
HL-60 Cells - enzymology
HL-60 Cells - pathology
Humans
LEUKEMIA
MORPHOLOGY
PROTEOLYSIS
SERINE
Serine Endopeptidases - metabolism
Serine Endopeptidases - physiology
Serine protease
Serine Proteinase Inhibitors - pharmacology
Staurosporine
Staurosporine - pharmacology
Subcellular Fractions
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Summary: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.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2005.10.003