(Circulation. 1998;97:227-229.)
© 1998 American Heart Association, Inc.
Cell Death and the Caspase Cascade
Stephen M. Schwartz, MD, PhD
From the Department of Pathology, University of Washington, Seattle.
Correspondence to Stephen M. Schwartz, Department of Pathology, University of Washington, Box 357335, Seattle, WA 98195-7335. E-mail steves@u.washington.edu
Key Words: Editorials • apoptosis • cells • proteins
The
article by Yaoita et al1 in this issue of
Circulation is the first of what will indubitably be many
articles on the role of the caspases in cell death. This is an
important event. Until 10 years ago, we could not define death at all.
Instead, we relied on the process of necrosis, the decay of the cell
after its death, as a way to tell us that cells had died. Typical
experiments involved applying a death stimulus for different time
periods and then waiting hours or days to see if the death stimulus had
effected a critical "point of no return."
This point of view changed dramatically starting with the work of
Horvitz in Caenorhabditis elegans. He defined three genes
that made up a genetic pathway determining cell death in the nematode.
These three genes were called ced-3, ced-4, and
ced-9. ced-3 turned out to be a cysteine
protease, that is, a protease with –SH in its active site instead of
serine's –OH. Today we know that there are at least 10 caspases, the
new name for cysteine proteases, and these form a cascade controlling
death in most situations studied thus far.2 3
The control of the caspases seems to depend on a simple principle: the
enzymes are normally inactive as proforms. Activation requires
proteolytic cleavage of the caspases at specific sites, and in most
cases, these sites are themselves substrates for caspases. So, by
analogy to coagulation, death is controlled by a cascade of . . . [Full Text of this Article]
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