Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis.
Citation:
Slee EA, Adrain C, Martin SJ, Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis., Journal of Biological Chemistry, 276, 2001, 7320 - 7326Download Item:
Abstract:
Members of the caspase family of cysteine proteases play central
roles in coordinating the stereotypical events that occur during
apoptosis. Because the major executioner caspases, caspase-3 and
caspase-7, exhibit almost indistinguishable activity toward certain
synthetic peptide substrates, this has led to the widespread view
that these proteases occupy functionally redundant roles within
the cell death machinery. However, the distinct phenotypes of mice
deficient in either of these caspases, as well as mice deficient in
both, is at odds with this view. These distinct phenotypes could be
related to differences in the relative expression levels of caspase-3
and caspase-7 in vivo, or due to more fundamental differences
between these proteases in terms of their ability to cleave natural
substrates. Here we show that caspase-3 and caspase-7 exhibit
differential activity toward multiple substrate proteins, including
Bid, XIAP, gelsolin, caspase-6, and cochaperone p23. Caspase-3 was
found to be generally more promiscuous than caspase-7 and
appears to be the major executioner caspase during the demolition
phase of apoptosis. Our observations provide a molecular basis for
the different phenotypes seen in mice lacking either caspase and
indicate that these proteases occupy nonredundant roles within
the cell death machinery.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
PI1/B038
Author's Homepage:
http://people.tcd.ie/martinsjDescription:
PUBLISHED
Author: MARTIN, SEAMUS
Type of material:
Journal ArticleCollections
Series/Report no:
Journal of Biological Chemistry276
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Biochemistry, cell death machineryMetadata
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